摘要:
J. CHEM. soc. PERKIN TRANS. 1 1993 1599 First Total Synthesis of ( ,+ )-Peridinin, ( k )-Pyrrhoxanthin and the Optically Active Peridinin Yumiko Yamano and Masayoshi Ito" Kobe Women s College of Pharmacy, Motoyamakita -machi, Higashinada-ku, Kobe 658, Japan The first total synthesis of peridinin 1 and pyrrhoxanthin 2 has been accomplished via the reaction of the C,,-epoxy formyl ester 21 with the C,-allenic sulfone 28 or the C,-acetylenic sulfone 39. A synthesis of optically active peridinin has also been achieved starting from the (4R,6R)-hydroxy ketone 5. The unique C,,-skeletal nor-carotenoids, peridinin 1 and Table 1 H NMR spectroscopic data of epoxides pyrrhoxanthin 2 were isolated from the planktonic algae, 2ax-H 2eq-Hdinoflagellates causing 'red tide' and their absolute stereostruc- (2'ax-H) (2'eq -H) tures were determined by the Jensen These carotenoids contain a 4-alkylidenebutenolide system carrying syn-group 51 1.54 1.38 an allene or an acetylene function in the main polyene chain.19 1.57 1.34 The main pigment peridinin is known as an auxiliary light 20 1.65 1.36 harvesting pigment for photosynthesis' in the sea. It is 48 1.58 1.41 52 1.40 1.63worthwhile for a synthetic chemist to take up the challenge of an ti-group 21 1.26 1.63the synthesis of such an attractive carotenoid, peridinin. In 22 1.37 1.67 previous communications, we have reported two Wittig 49 1.39 1.63 methods '9' directed towards the synthesis of carotenoidal 1 1.26 1.63 alkylidenebutenolides such as 4 (Scheme l), but they were 2 1.22 1.60 found to be inappropriate for the preparation of compounds 35 ca.1-40 1.66 containing a longer conjugated polyene chain because of the drastic reaction conditions employed. As an alternative method, we recently developed a novel synthetic method (a sulfone method) 8,9 which is the reaction of the conjugated fluoromethanesulfonimide (Tf2NPh)' in the presence of LDA formyl ester 3 with various allylic sulfones in the presence of gave the enol triflate 7 (89%), which underwent a coupling lithium diisopropylamide (LDA) at -78 "C(Scheme 1). By the reaction l3 with methyl acrylate in the presence of palladium application of this methodology, the first total synthesis of the catalyst to afford the diene ester 8 (93%). Reduction of the ester 4-alkylidenebutenolide carotenoids, ( f)-peridinin 1, ( f)-pyr-group in 8 with lithium aluminium hydride (LAH) followed by rhoxanthin 2, and optically active peridinin was accomplished acetylation gave the allylic acetate 9 (80%), which was treated previously.'.'' The present paper is concerned with a full with sodium sulfinate catalysed by Pd(PPh,)4'4 to provide the account of the experiments.allylic sulfone 10 (89%). Introduction of a methoxycarbonyl group into 10 followed by alkylation with ally1 bromide and Synthesis of the C, ,-Epoxy Formyl Ester 21.-Treatment of subsequent deprotection gave the compound 13 (61%). the tert-butyldimethylsilyl (TBS) ether 6 (Scheme 2) of the 4- Regioselective oxidation of 13 at the terminal vinyl group with hydroxy-2,2,6-trimethylcyclohexanone5 with N-phenyltri- sodium periodate and a catalytic amount of osmium tetroxide HOb..W 50 +c) I *w ; Peridinin 1 X Y Pyrrhoxanthin2 1600 J.CHEM. soc. PERKIN TRANS. I 1993 RCH=PPh, RCHO Wiltig method 4 R = conjugated C02Me polyene chain @A? f RCHSQPh LDAI-78°C3 THF-hexane (1:l) sulfone method Scheme 1 7 8 R=C02Me' 9 R=CH20Ac 10 R=CH2S02Ph 11 viii = TBsI,ii R=H 14 R=OAc ROm;;o 15 R=H 19 R=H 16 R=Ac 20 R=Ac Ix 17 R=H 21 R=H 18 R=Ac 22 R=Ac Scheme 2 Reagents: i, TBSCl, Et,N, DMAP, CH,Cl,; ii, LDA, Tf,NPh, THF; iii, CH,=CHCO,Me, PdCl,(PPh,),, Et,N, DMF; iv, LAH, Et,O, then Ac,O, Py; v, PhSO,Na, Pd(PPh,),, THF-MeOH; vi, BuLi, ClCO,Me, THF; vii, NaH, BrCH,CH=CH,, DMF; viii, TBAF, THF; ix, OsO,, NaIO,, dioxane-H,O, then A1203; x, I,, Et,O-hexane; xi, MCPBA, CH,Cl, J.CHEM.soc. PERKIN TRANS. I 1993 1601 hr 26 R'= H, R~=CHO 27 R' = Ac, R2= CH20Ac 28 R' = Ac, R2= CH2SO2P 31 R=OH V 32 R=CrPhSP+ ' 29 R'=H,&CHO 30 R' = Ac, R2=CH20Ac - 28 18 vi A& 33 34 For X and Y see structures1 and 2 1 R'=H,R~=X 35 R'=AC,&X 2 R'=H,R~=Y iv 37 R' = H, R2= CHO 38 R' = Ac, R2= CH~OAC R'=Ac, R2=CH2S02Ph ;: 4: Scheme 3 Reagents and conditions: i, LiC1, MsC1, y-collidine, DMF, then PPh,; ii, HC(OMe),, H+, MeOH; iii, NaOMe, CH,Cl,, then H+; iv, NaBH,, MeOH, then Ac,O, Py;v, PhSO,Na, propan-2-ol-H20, reflux; vi, LDA, THF, -78 OC and the subsequent elimination of the sulfone group with A1,0, afforded a mixture of the 9E-formyl ester* 15 (21%) and the 9Z- isomer 17 (17%) which were cleanly separated by preparative HPLC (pHPLC).The stereochemistry around the newly formed 9,lO-double bond was determined from the comparison of the chemical shifts for 8-Hs and 10-Hs in both isomers. In the 9Z-isomer 17, 8-H and 10-H signals appear at 6 6.22 and 6.09, respectively, whereas the corresponding signals (8-H; 6 6.67 and 10-H;6 6.66) in the 9E-isomer 15 are at lower field owing to the anisotropic effect of the formyl and ester groups, respectively. * We have employed the numbering system used in the retinoids and carotenoids. Treatment of the 9E-isomer 15 with a catalytic amount of iodine provided a mixture (ca.3 :4) of 15 and 17. Epoxidation of 17 with rn-chloroperbenzoic acid (MCPBA) gave a mixture of the syn-(f3)-epoxide 19 (56%) and the anti-(a)-epoxide 21 (19%). Relative configurations between hydroxy and epoxy groups in the two isomers were confirmed by 'H NMR spectroscopic data (see Table 1). Synthesis of the All-E-C,,-Allenic Sulfone 28.-The all-E-C,,-allenic sulfone 28 was synthesized from the C,,-allenic apocarotenals 26 and 29 which were previously prepared uia a Wittig condensation of the C,,-allenic aldehyde 23 with the C,-phosphonium bromide 25 (Scheme 3). At this time, this Wittig condensation was modified by use of the C7- 1602 J. CHEM. SOC. PERKIN TRANS. 1 1993 0 cII ...f (39-21 Scheme 4 phosphonium chloride 24 instead of 25. Reduction of the formyl group in 26 with NaBH, followed by acetylation gave the acetate 27, which was refluxed with sodium sulfinate in propan-2-01 and water to afford the sulfone 28 (63% from 26). The 1lZ-apocarotenal 29 was also converted into the al1-E- sulfone 28 (5 1%) through 30in the same manner as in the case of the all-E-isomer 26. Isomerization might occur during sulfonization of the acetate 30 with heating. Thus, 28 was synthesized in 5 steps from CIS-aldehyde 23 in 51% yield without separation of the isomers 26 and 29. The structure of 28 was determined from its 'H NMR spectrum. Synthesis of (5)-Peridinin 1.-In order to accomplish the total synthesis of 1, synthesis of peridinin acetate 35 (Scheme 3) was achieved as the preliminary experiment using the 3-acetoxy compound 14 (Scheme 2) prepared previously.' First, regioselective epoxidation at the 5',6'-double bond was examined in the C,,-skeletal compound 33, which was synthesized via reaction of the allenic sulfone 28 with the 3- acetoxy-C, ,-formy1 ester 18 derived from 14.The carbanion prepared from the sulfone 28 and LDA in a mixture (1 : 1) of tetrahydrofuran (THF) and hexane was treated with the formyl ester 18 at -78 "C to afford a mixture (20%; ca. 6: 1) of the skeletal compound 33 and its 11'E-isomer 34.The structures of two isomers were confirmed on the basis of their spectral data (see Experimental section). In the IR spectrum, both isomers showed an absorption (vlcm-' 1745) due to an a,p-unsaturated y-lactone.The stereochemistry around the newly formed 11',12'-double bond was determined from the chemical shifts for 10'-Hs (33; 6 7.03 and 34;6 7.41) in both isomers on the basis of the empirical rule." Unfortunately, the epoxidation of 33 with MCPBA gave complicated products, in which only a small amount of the desired peridinin acetate 35 was contained (detection only by HPLC). In contrast, treatment of the formyl ester 18with MCPBA resulted in the regioselective epoxidation at the 5,6-double bond to give a mixture of the syn-(P)-epoxide 20 (47%) and anti-(a)-epoxide 22 (20%) (Scheme 2). Then, the condensation of the sulfone 28with the anti-epoxide 22 gave the peridinin acetate 35 (13%) without the opening of the epoxide ring. Spectral properties of synthetic 35* were identical with those of a semi-synthetic sample prepared from authentic peridinin? (Scheme 3).Based on the synthesis of peridinin acetate, the sulfone 28 was * This seems to be a mixture of diastereoisomers. 7 This was kindly supplied by Dr. Y. Tanaka, Kagoshima University, Japan. A mixed HPLC of the synthetic and the natural pigment showed no separation. condensed with the 3-hydroxy-anti-epoxide 21 in the presence of LDA to provide the condensed product (18%), repeated purification of which by pHPLC in the dark led to peridinin 1 and its 11'E-isomer 36 in pure form, respectively. Spectral properties of the synthetic peridinin * were in good agreement with those of natural specimen.? Synthesis of ( k )-Pyrrhoxanthin 2.-The total synthesis of (&)-pyrrhoxanthin 2 was also accomplished by the application of the sulfone method.Similar treatment of the known C22- acetylenic apocarotenal37 as in the case of the preparation of the allenic sulfone 28 gave a mixture of all-E-acetylenic sulfone 39 (31%) and its 92-isomer 40(31%). The exceptional stability of 92-isomers in the case of carotenoids with a 7,8-triple bond has been noted.16 Thus, the isomerization occurred during sulfonization of the acetate 38with heating. Condensation between the acetylenic sulfone 39 and the anti-epoxide 21 in the presence of LDA produced a mixture (13%; ca. 1 : 1) of pyrrhoxanthin 2 and its 11'2-isomer, which was cleanly separated by pHPLC in the dark.Spectral properties of the synthetic 2 were in accordance with those rep~rted.~ Synthesisof Optically Active Peridinin.-Optically active C, 5-epoxy formyl ester 21 was prepared (Scheme 4) from the readily available chiral hydroxy ketone 5 l7 in the same pathway as described in the synthesis of racemic 21 (Scheme 2). The optical purity was determined (88% e.e.) by HPLC analysis of the camphanate 42. The optically active C2,-allenic sulfone 28 was also prepared from the same chiral synthon 5 according to the route as shown in Scheme 5. Treatment of the trimethylsilyl (TMS) ether 43 of the (4R,6R)-hydroxy ketone 5 with the lithium salt of the TMS ether of (E)-3-methylpent-2-en-4-yn-1-01 gave the hydroxy compound 44which, without purification, was deprotected and then acetylated to afford a mixture (7: 1) of the hydroxy diacetates 45 and 46 (82% from the ketone 43).Its recrystallization gave a major diastereoisomer 45 in pure form, whose optical purity (97% e.e.) was determined by use of the camphanate 50 of the allenic aldehyde 23. The stereochemistry of these isomers were established by 'H NMR spectroscopy including 2D NOESY experiment: 3-Hs (45; 6 4.95, quint, J 3 and 46;6 5.00, quint, J 3) of both isomers were assigned as equatorial (see Scheme 5) from their small J values. 5-Hs (45; 6 2.25, dqd, J 13, 6.5, 4 and 46;S 2.24, dqd, J 13, 6.5,4) of both isomers were axial, owing to their large J4ax,5values (1 3 Hz).In 2D NOESY experiments, the cross-peaks between 6-OH and 1ax methyl protons were not observed in 46 but were observed in 45. Thus the conformations of these isomers must be as shown in Scheme 5. It is considered that the attack of the C,-acetylenic J. CHEM. SOC. PERKIN TRANS. 1 1993 (34-44(4R,6R)-5 R=Hi (4R,6R)43 R=TMS I I "1 (3447 (39-48 (39-49 CH2S02Ph AcO 3 '"''OH = (35)-28(39-23 R=H viii (3s)-21 vii L,(33-50 R=Cp Peridinin1 +1l'f-Isomer36 Scheme 5 Reagents and conditions: i, TMSCl, Et,N, Et,O; ii, BuLi, Et,O; iii, p-TsOH, MeOH, then Ac,O, Py;iv, POCl,, Py,75 "C; v, MCPBA, CH,Cl,; vi, DIBAL, CH,CI,, then MnO,; vii, TBAF, THF, then (-)-CpCl, Et,N, DMAP, CH,Cl,; viii, LDA, THF, -78 "C component on the less hindered side of the ketone 43 resulted in the formation of 45.Dehydration of 45 with phosphorus oxychloride in pyridine gave the optically active enyne diacetate 47 (67%). Conversion of (3R)-47 into the optically active C, ,-allenic aldehyde 23 "." was carried out according to the synthesis of the racemic 23." Treatment of 47 with MCPBA led to a mixture of the syn-(P)-epoxide 48 (24%) and anti-(a)-epoxide 49 (20%). Reduction of the anti-epoxide 49 with diisobutyl aluminium hydride (DIBAL) followed by treatment with MnO, gave the allenic aldehyde 23 (84%). The C,,-allenic sulfone (3S)-28was prepared from (3S)-23in the same way as described in the synthesis of the racemic 28 (Scheme 3). Condensation between the allenic sulfone (3S)-28 and the formyl ester (3S)-21in the presence of LDA produced a mixture (1 1%; ca.1 :1) of optically active peridinin 1 and its 11'E-isomer which was cleanly separated by pHPLC in the dark (Scheme 5). Spectral data [UV-VIS, IR, NMR and MS] were identical with those of the natural specimen. In addition, its CD spectrum (Fig. 1) was nearly superimposable on that reported by the Jensen group.3 This is the first total synthesis of optically active peridinin. H NMR Spectral Properties of Epoxides.-Conformation of a number of epoxides prepared in the present work was determined by the comparison of their 'H NMR spectroscopic data (Table 1) with those of the known syn-and anti- epoxides 51 and 52. Consequently, characteristic properties were found in the chemical shifts of 2-Hs in these epoxides.In anti-epoxides, chemical shift correlation between 2ax-Hs and 2eq-Hs is normal. However, in syn-epoxides, 2ax-Hs situated close to the oxygen of the epoxy ring are found at lower field 51 52 symEpoxide 0 w -2 4 4 -6 Fig. 1 CD spectra in EPA (Et,O-isopentane-EtOH, 5:5:2) of peridinin 1 and its 11'E-isomer 36. Natural peridinin . . . -;synthetic peridinin -; 1 1'E-isomer36 -----than 2eq-Hs. This deshielding may be ascribed to van der Waals interactions between the 2ax-H and the oxygen atom or to the effect of lone-pair electrons of the oxygen. The same correlations were observed in the literature.20*21 These results can be effectively used to determine the stereochemistry of 5,6- epoxy compounds having an oxygen functional group at the 3- position.Experimental M.p.s are uncorrectred. UV-VIS spectra were recorded on a Shimadzu UV-200 or UV-200s or UV-160 instrument and IR spectra on a Shimadzu IR-27G spectrometer in a chloroform solution. 'H NMR spectra at 60, 200 or 500 MHz were measured on a JEOL JNM-PMX 60, or a Varian XL-200 or a Varian VXR-500 superconducting FT-NMR spectrometer, respectively, in deuteriochloroform solutions using tetramethyl- silane as an internal reference. 13C NMR spectra at 50 MHz were determined on a Varian XL-200 superconducting FT- NMR spectrometer in deuteriochloroform solutions using tetramethylsilane as an internal standard. Mass spectra were taken on a Hitachi M-80 or a JEOL JMS-SX 102.Optical rotations were measured on a JASCO DIP-181 or a JASCO DIP-370 and CD spectra in EPA (Et,O-isopentane-EtOH, 5 :5 :2) solution on a JASCO J-5OOC. Column Chromatography (CC) was performed on silica gel: Merck Art. 7734 for open columns and Merck Art. 7739 for short columns under reduced pressure. Low-pressure column chromatography was conducted on a Yamazen Low Pressure Liquid Chromatography System using a Lobar Column (Merck LiChroprep Si60). Preparative J. CHEM. SOC. PERKIN TRANS. 1 1993 TLC (pTLC) was performed on silica gel plates (Merck silica gel 60F254 pre-coated plates, 0.25 or 0.5 mm thickness). Analytical and preparative HPLC was carried out on Shimadzu LC-3A, 5A, and 6A instruments with a UV-VIS detector.Unless otherwise stated, solvent extracts were dried over anhydrous sodium sulfate and all operations were carried out under nitrogen or argon. Evaporation of the extract or the filtrate was carried out under reduced pressure. Ether refers to diethyl ether. The NMR assignments are given using the carotenoid numbering system except for compounds 6, 7 and 43. Synthesis of Racemic Peridinin 1 4-tert-Butyldimethylsilyloxy-2,2,6-trimethylcyclohexanone 6.-TBSC1(15.0 g, 100 mmol) was added to a stirred solution of the hydroxy ketone 5" (14.50 g, 93 mmol), triethylamine (14.3 cm', 102 mmol) and 4-dimethylaminopyridine (DMAP) (12.0 g, 98 mmol) in dry CH,Cl, (30 cm3)at 0 "C. The mixture was stirred at room temp.for2 h, poured into chilled water and extracted with ether. The extracts were washed successively with aqueous 5% HCl, saturated aqueous NaHCO, and brine. Evaporation of the dried solution followed by distillation (98- 102 "C/0.08 mmHg) gave 6 (23.42 g, 93%) as a colourless oil; v,,,/cm-' 1700 (M);dH(6O MHz) 0.08 (6 H, s, SiMe x 2), 0.87 (9 H, s, Bu'), 1.00 (3 H, d, J6,6-Me), 1.03 and 1.33 (each 3 H, s, gem-Me) and 4.23 (1 H, m, 4-H). 4-tert-Butyldimethylsilyloxy-2,6,6-trimethylcyclohex-1-enyl TriJIuoromethanesuyonate 7.-A solution of butyllithium (BuLi) (1.59 mol dm-, in hexane; 23.1 cm3, 37 mmol) was added to a stirred solution of diisopropylamine (5.13 cm3,37 mmol) in dry THF (75 cm3) at -78 "C and the mixture was stirred for a further 30 min.To this LDA solution was added dropwise a solution of the ketone 6 (9.00 g, 33 mmol) in dry THF (75 cm3). Upon completion of the addition, the mixture was stirred for 1 h at -78 "C, after which a solution of Tf,NPh (12.50 g, 35 mmol) in dry THF (75 cm3) was added dropwise at the same temperature. The ice-cooled mixture was stirred for 5 h. The reaction was quenched with saturated aqueous NH4Cl. After evaporation of THF, the residue was extracted with ether. The extracts were washed with brine, dried and evaporated. The residue was purified by CC (ether-hexane, 4 :96) to afford the vinyl triflate 7 (1 1.88 g, 89%) as a colourless oil; vmax/cm-' 1398 and 1130 (OSO,);dH(200 MHz) 0.08 (6 H, s, SiMe x 2), 0.89 (9 H, s, Bu'), 1.15 and 1.21 (each 3 H, s, gem-Me), 1.75 (3 H, s, 2-Me),2.16(1 H,ddd, J17,9, 1,5-H),2.36(1 H, brdd, J17,6, 5-H) and 4.02 (1 H, m, 4-H); &(50 MHz) 17-59 (4-CH3), 36.75 (C-2), 64.26 (C-4), 118.76 (4, J 318, CF,), 123.91 (C-6) and 149.05 (C- 1) (Found: m/z 402.1 51.C, ,H2,F,04SSi requires M, 402.151). Methyl (E)-3-(4-tert-Butyldimethylsilyloxy-2,6,6-trimethyl-cyclohex-1-enyl)prop-2-enoate 8.-PdCl,(PPh,), (330 mg, 0.47 mmol) was added to a solution of the vinyl triflate 7 (6.49 g, 16 mmol), methyl acrylate (5.73 an3,65 mmol) and triethylamine (7.94 cm3, 57 mmol) in dry dimethylformamide (DMF) (45 cm3). The mixture was heated and stirred at 75 "C for 22 h. After cooling, the reaction mixture was diluted with ether and washed with aqueous 5% HCl, saturated aqueous NaHCO, and brine.Evaporation of the dried solution gave a residue which was purified by CC (ether-hexane, 7 :93) to afford the dienyl ester 8 (5.10 g, 93%) as a colourless oil; 1,,,(EtOH)/nm 278; vmax/cm-' 1707 (conj. C0,Me); dH(200 MHz) 0.08 (6 H, s, SiMe x 2), 0.90 (9 H, s, Bu'), 1.08 and 1.10 (each 3 H, s, gem-Me), 1.48 (1 H, t, J 12.5, 2ax-H), 1.66 (1 H, ddd, J 12.5,4, 1.5,2eq-H), 1.76 (3 H, s, 5-Me), 2.08 (1 H, br dd, J17.5,9,4ax-H), 2.27(1 H, brdd, J 17.5,6,4eq-H), 3.76(3 H, s, CO,Me),3.94(1 H,m,3-H),5.82(1 H,d, J16,8-H)and7.37(1 J. CHEM. SOC. PERKIN TRANS. 1 1993 H, br d, J 16, 7-H) (Found: m/z338.228. Cl9H3,O,Si requires M,338.228). (E)-3-(4-tert-Butyldimethylsilyloxy-2,6,6-trimethylcyclohex-1-enyl)allyl Acetate 9.-A solution of the dienyl ester 8 (1 1.97 g, 35 mmol) in dry ether (200 cm3) was added dropwise to a stirred suspension of LAH (1.01 g, 27 mmol) in dry ether (200 cm3) at 0 "C and the mixture was stirred at 0 "C for 30 min. The excess of LAH was decomposed by dropwise addition of water.The mixture was extracted with ether and the extracts were washed with brine and dried. Evaporation of the solvent gave the hydroxy compound, which without purification was dissolved in pyridine (Py)(50 cm3) and acetic anhydride (10 cm3). The mixture was stirred at room temperature for 16 h, poured into ice-water and extracted with ether. The extracts were washed successively with aqueous 5% HCl, saturated aqueous NaHCO, and brine. Evaporation of the dried extracts gave a residue which was purified by CC (ether-hexane, 1 :9) to afford the acetate 9 (9.97 g, 80%) as a colourless oil; v,,/cm-' 1730 (OAC); 6&00 MHz) 0.08 (6 H, S, SiMe x 2), 0.90 (9 H, S, Bu'), 1.01 and 1.03 (each 3 H, s, gem-Me), 1.67 (3 H, s, 5-Me), 2.07 (3 H, s, OAc), 3.93 (1 H, m, 3-H), 4.62 (2 H, d, J6.5, 9-H,), 5.52 (1 H, dt, J 16,6.5,8-H) and 6.13 (1 H, br d, J 16,7-H) (Found: m/z 352.245.C2,H,,03Si requires M, 352.243). (E)-[3-( 4-tert -Butyldimethylsilyloxy-2,6,6-trimethylcyclohex-1-enyl)allyl]sulfonylbenzene 10.-A solution of Pd(PPh,), (735 mg, 0.64 mmol) in THF (18 cm3)was added to a mixture of the acetate 9 (4.49 g, 13 mmol) and PhS02Na.2H,0 (2.81 g, 14 mmol) in MeOH (9 cm3) and THF (18 cm3)and the reaction mixture was stirred at room temperature for 1 h.After the reaction had been quenched by the addition of aqueous potassium cyanide (150 mg, 2.3 mmol), the mixture was extracted with ether. The extracts were washed with brine, dried and evaporated to give an oil which was purified by short CC (ether-hexane, 1 :3) to provide the sulfone 10 (4.91 g, 89%) as colourless crystals, m.p. 82-83 "C; vmaX/cm-' 1310 and 1300 (split) (SO,) and 1132 (SO,); dH(200 MHz) 0.06 (6 H, S, SiMe x 2), 0.89 (9 H, s, Bu'), 0.85 and 0.91 (each 3 H, s, gem-Me),1.39(1H,t,J12,2ax-H),1.59(3H,s,5-Me),1.98(1H,br 1605 Methyl (E)-2-[2-( 4- ter t -Bu ty ldimethy lsily loxy-2,6,6-tri-me thy Icy clo hex- 1-eny 1) vinyl] -2-pheny lsulfony(pent -4-enoa te 12.-A suspension of sodium hydride (60% oil dispersion; 0.46 g, 11.5 mmol) in dry DMF (12 cm3) was added to a stirred solution of the ester 11(4.08 g, 8.3 mmol) in dry DMF (22 cm3) at 0 "C. The mixture was stirred at room temperature for 40 min after which allyl bromide (0.79 cm3, 9.1 mmol) was added to it at 0 "C.The mixture was then stirred at 0 "C for 10 min and at room temperature for 15 min. After the reaction had been quenched with saturated aqueous NH,CI, the mixture was extracted with ether. The extracts were washed with brine, dried and evaporated to give a residue which was purified by short CC (ether-hexane, 3:7) to provide the allyl ester 12 (4.32 g, 98%) as a colourless oil; v,,,/cm-' 1735 (CO,Me), 1638 (M), 1312 and 1300 (split) (SO,) and 1138 (SO,); dH(200 MHz) 0.08 (6 H, s, SiMe x 2), 0.91 (9 H, s, Bu'), 1.02 and 1.06 (9/2 H and 3/2 H, each s, gem-Me), 1.68 and 1.72 (each 3/2 H, s, 5-Me), 3.06 (2 H, m, 10-H,), 3.70 (3 H, s, C02Me), 3.95 (1 H, m, 3-H), 5.11 (1 H, s-like, 12-H), 5.17 (1 H, d-like, J7, 12-H), 5.60(1 H, m, 11-H), 5.76 and 5.77 (each 1/2 H, d, J 16,8-H), 6.36 (1 H, br d, J 16, 7-H), 7.51-7.72 (3 H, m, ArH) and 7.81-7.87 (2 H, m, ArH) (Found: m/z391.267.C23H3903Si requires M -S02Ph, 391.267). Methyl (E)-2-[2-(4-Hydroxy-2,6,6-trimethylcyclohex-1-enyl)vinyl]-2-phenylsulfonylpent-4-enoate 13.-A solution of tetrabutylammonium fluoride (TBAF) (1 mol dm-, in THF; 80 an3,80 mmol) was added to a solution of 12 (5.50 g, 10 mmol) in THF (100 cm3) and the mixture was stirred at room temperature for 4 h.This was diluted with ether and the organic layer was washed with brine. Evaporation of the dried solvent gave a residue which was purified by short CC (MeOH- CH,CI,, 2:98) to provide 13(3.62 g, 84%) as a colourless oil; v,,,/cm-' 3605 and 3450 (OH), 1735 (CO,Me), 1315 and 1302 (split) (SO,) and 1140 (SO,); 6,(200 MHz) 1.04 and 1.07 (9/2 H and 3/2 H, each s, gem-Me), 1.70 and 1.74 (each 3/2 H, s, 5-Me), 3.06 (2 H, m, 10-H,), 3.70 (3 H, s, CO,Me), 3.98 (1 H, m, 3-H), 5.10 (1 H, s-like, 12-H), 5.16 (1 H, d-like, J 8,12-H), 5.58 (1 H, m, 11-H), 5.77 (1 H, d, J 16, 8-H), 6.36 (1 H, br d, J 16, 7-H), 7.48-7.71 (3 H, m, ArH) and 7.80-7.86 (2 H, m, ArH) (Found: m/z 277.180. Cl7H2,O3 requires M -SO,Ph, 277.180).(2E/Z,4E)-5-(4-Hydroxy-2,6,6-trimethylcyclohex-1-enyl)-3-dd, J18,9.5,4ax-H),2.17(1 H, brdd, J18,6,4eq-H),3.87(1 H, m, 3-H), 3.90 (2 H, d, J7.5,9-H2), 5.32 (1 H, dt, J 16,7.5,8-H), 5.96 (1 H, br d, J 16, 7-H), 7.49-7.66 (3 H, m, ArH) and 7.86 7.92 (2 H, m, ArH) (Found: m/z434.231 C2,H,,03SSi requires M, 434.231) (Found: C, 66.1; H, 8.85; S, 7.6. C,,H,,O,SSi requires C, 66.31; H, 8.81; S, 7.38%). Met hy 1 ( E)-4-(4-tert -Butyldimethylsilyloxy-2,6,6-trimethyl-cyclohex-1-enyl)-2-phenylsulfonylbut-3-enoate11.-A solution of BuLi (1.59 mol dmV3 in hexane; 13.8 cm', 22 mmol) was added to a stirred solution of the sulfone 10 (4.78 g, 11 mmol) in dry THF (80 cm3) at -78 "C. The mixture was stirred for a further 30 min after which methyl chloroformate (1.72 cm3, 13 mmol) was added to it and stirring continued at -78 "C for 20 min.The reaction was quenched with saturated aqueous NH,Cl. After evaporation of THF, the residue was extracted with ether. The extracts were washed with brine, dried and evaporated to afford a residue which was purified by low pressure column chromatography (ether-hexane, 1 :3) to provide the ester 11 (3.99 g, 74%) as a colourless solid and recovered starting material (1.03 g, 22%); v,,,/cm-' 1738 (CO,Me), 1315 and 1300 (split) (so,)and 1139 (so,);dH(200 MHz) 0.07 (6 H, s, SiMe x 2), 0.90 (9 H, s, Bur), 0.92 and 0.93 (each 3/2 H, s, 1-Me), 0.98 (3 H, s, 1-Me), 1.64 and 1.66 (each 3/2 H, s, 5-Me), 3.74 (3 H, s, CO,Me), 3.90 (1 H, m, 3-H), 4.61 (1 H, d, J9.5,9-H), 5.50 and 5.52 (each 1/2 H, dd, J 16,9.5, 8-H),6.15and6.17(each 1/2H,brd, J16,7-H),7.51-7.72(3H, m, ArH) and 7.85-7.93 (2 H, m, ArH) (Found: m/z 351.235.C,,H,,O,Si requires M -SO,Ph, 351.232). methoxycarbonylpenta-2,4-dienall5and17.-Osmium tetroxide (40 mg, 0.16 mmol) was added to a solution of 13(4.80 g, 11 mmol) in dioxane (45 cm3) and water (15 cm3) at room temperature and the mixture was stirred for 5 min. Sodium metaperiodate (5.70 g, 27 mmol) was then added in small portions to the mixture over 30 min. After being stirred at room temperature for 3 h, the reaction mixture was diluted with ether and washed with brine. Evaporation of the dried solvent gave an oil which was dissolved in ether (300 cm3).To this solution was added aluminium oxide for CC (Merck Art. 1064,50 g) and the mixture was stirred at room temperature. Upon disappearance of the TLC spot of the starting material, aluminium oxide was filtered off. Evaporation of the filtrate gave a residue which was purified by short CC (acetone-hexane, 1 :1) followed by pHPLC [LiChrosorb Si 60 (7 pm) 2.5 x 25 cm; acetone-hexane, 1:31 to provide the 9E-formyl ester 15 (658 mg, 21%) and the 9Z-isomer 17 (542 mg, 17%), as yellow oils, respectively. Compound 15: A,,,(EtOH)/nm 210, 270sh and 325sh; v,,,/cm-' 3600 and 3440 (OH), 1730 (C0,Me) and 1670 (conj. CHO); dH(200 MHz) 1.11 and 1.12 (each 3 H, s, gem-Me), 1.49 (1 H, t, J 12, 2ax-H), 1.81 (3 H, s, 5-Me), 2.10 (1 H, dd, J 17,9,4ax-H), 2.44 (1 H, br dd, J 17, 5,4eq-H), 3.87 (3 H, s, CO,Me), 4.02 (1 H, m, 3-H), 6.59 (I H, br d, J 16,7-H), 6.66(1 H,d,.r7.5,10-H),6.67(1 H,d, J16,8-H)and 10.07(1 H, J.CHEM. SOC. PERKIN TRANS. I 1993 d, J 7.5, CHO) (Found: m/z 278.152. C,,H,,O4 requires M, 278.152). Compound 17: A,,,(EtOH)/nm 265 and 33 1; vmax/cm- '3610 and 3450 (OH), 1730 (C0,Me) and 1670 (conj. CHO); dH(200 MHz) 1.09 and 1.10 (each 3 H, s, gem-Me), 1.47 (1 H, t, J 12, 2ax-H), 1.78 (3 H, s, 5-Me), 2.07 (1 H, br dd, J 17, 10,4ax-H), 2.43 (1 H, br dd, J 17, 5,4eq-H), 3.95 (3 H, s, CO,Me), 4.00 (1 H, m, 3-H), 6.09 (1 H, d, J7.5, 10-H), 6.22 (1 H, d, J 16, 8-H), 6.65(1 H, brd, J16,7-H)and9.79(1 H,d, J7.5,CHO)(Found: m/z 278.152. CI6H2,O4 requires M, 278.152).Isomerization of the 9E-Formyl Ester 15.-A solution of iodine in hexane (0.01%, w/v; 250 cm3)was added to a stirred solution of the formyl ester 15(1.12 g, 4 mmol) in ether-hexane (5 :3; 400 cm3) and the mixture was stirred at room temperature for 30 min. It was then washed with aqueous 1% sodium thiosulfate and brine, dried and evaporated to give an oil. This was purified in the same way as described above to provide 15 (370 mg, 33%) and 17 (522 mg, 46%). Epoxidation of the 9Z-Formyl Ester 17.-A solution of MCPBA (396 mg, 2.30 mmol) in CH,CI, (22 cm3) was added to a cooled solution of 17 (426 mg, 1.53 mmol) in CH,CI, (8 cm3). After being stirred at 0 "C for 5 h, the reaction mixture was diluted with CH,Cl, and washed with saturated aqueous NaHCO, and brine.Evaporation of the dried solution gave a residue which was purified by pHPLC [LiChrosorb Si 60 (5 pm) 1.O x 30 cm; MeOH-ether-hexane, 3 :50 :471 to provide the syn-epoxide 19 (254 mg, 56%) and the anti-epoxide 21 (87 mg, 19%), as pale yellow oils, respectively. Compound 19: L,,,(EtOH)/nm 283; v,,,/cm-' 3610 and 3450 (OH), 1730 (CO,Me), 1675 (conj. CHO) and 1622 (W);6,(200 MHz) 1.01, 1.17 and 1.21 (each 3 H, s, gem-Me and 5-Me), 1.34 (1 H, ddd, J 13, 4, 1, 2eq-H), 1.57 (1 H, dd, J 13, 11, 2ax-H), 1.87 (1 H, dd, J 15, 9, 4ax-H), 2.21 (1 H, ddd, J 15, 7, 1, 4eq-H), 3.87 (1 H, m, 3-H), 3.94 (3 H, s, CO,Me), 6.15 (1 H, d, J7.5, 10-H), 6.37 (1 H, d, J 16, 8-H), 6.46 (1 H, d, J 16, 7-H) and 9.84 (1 H, d, J 7.5, CHO) (Found: m/z 294.146.C16H2,05 requires M, 294.146). Compound 21: L,,,(EtOH)/nm 283; vmax/cm-' 3600 and 3420 (OH), 1730 (CO,Me), 1675 (conj. CHO) and 1622 (W); dH(200 MHz) 0.99, 1.16 and 1.21 (each 3 H, s, gem-Me and 5-Me), 1.26 (1 H, dd, J 12.5, 11, 2ax-H), 1.63 (1 H, ddd, J 12.5, 3.5, 1.5,2eq-H), 1.65 (1 H, dd, J 14,9,4ax-H), 2.42 (1 H, ddd, J [1R*(2E,4E,SE/Z,8E)2,,4P]-(k)-1 1 -(2,4-Dihydroxy-2,6,6-trimethylcyclohexylidene)-2,9-dimethylundeca-2,4,6,8,1O-pen-taenal 26 and 29.-To a solution of the C,-phosphonium chloride 32 (1.10 g, 2.6 mmol) in MeOH (5 cm3), were added an acidic solution (1 cm3)prepared from toluene-p-sulfonic acid (p-TsOH) (150 mg) and H3PO4 (0.2 cm3) in MeOH (50 cm3), and methyl orthoformate (1 cm3). The reaction mixture was stirred at room temperature for 18 h and neutralized with NaOMe until just before the red colour of a ylide appeared to give a Wittig salt 24 solution.To this solution, were added a solution of the C, ,-allenic aldehyde 23 ' (316 mg, 1.26 mmol) in CH,Cl, (1 5 cm3) and a NaOMe solution prepared from Na (70 mg) and MeOH (2 cm3). After being stirred at room temperature for 30 min, the reaction mixture was poured into ice-water and extracted with ether. The extracts were shaken with aqueous 3% HCl until the fine structure in the UV spectrum disappeared and then washed with saturated aqueous NaHCO, and brine. Evaporation of the dried extract provided a residue which was purified by short CC (acetone-hexane, 3 :7) to afford an isomeric mixture of the allenic apocarotenals. pHPLC separation [LiChrosorb Si 60(7 pm) 2.5 x 25 cm; propan-2-ol-THF-hexane, 1 :35 :641 of the mixture provided the all-E-isomer 26 (1 68 mg, 41 %)and the 112-one 29 (1 64mg, 38%), as orange solids, respectively.These isomers were identical with the samples prepared previously. ' [1f3,3a,4R*(3E,5E,7E,9E)]-( k)-3-Hydroxy-4-(3,10-dimethyl-11 -phenylsulfonylundeca-1,3,5,7,9-~entaenylidene)-3,5,5-trimethylcyclohexyl Acetate 28.--(a) From the all-E- apocarotenal26. NaBH, (1 6 mg, 0.42 mmol) was added to an ice-cooled solution of 26 (290 mg, 0.85 mmol) in MeOH (12 cm3). The mixture was stirred for 15 min and then poured into ice-water and extracted with ether. The extracts were washed with brine and dried.Evaporation of the solvent gave the triol, which without purification was dissolved in Py (1 1 cm3) and acetic anhydride (3.5 cm3). The mixture was stirred at room temperature for 15 h, poured into ice-water and extracted with ether. The extracts were washed with aqueous 5% HCl, saturated aqueous NaHCO, and brine. Evaporation of the dried extracts provided the diacetate 27 (320 mg); A,,,(EtOH)/ nm 315sh, 329, 345 and 364; v,,,/cm-' 3600 and 3420 (OH), 1930(C====)and 1725 (OAc). To a solution of the diacetate 27 (320 mg, 0.78 mmol) in propan-2-01 (6 cm3) were added water (2 cm3) and PhSO,Na-2H2O (204 mg, 1.02 mmol) and the mixture was refluxed for 20 h. After cooling, the reaction mixture was 14,5, 1.5,4eq-H),3.91(1H,m,3-H),3.94(3H,s,CO,Me),6.14 (1 H, d, J7.5, 10-H), 6.38 (1 H, d, J 16,8-H), 6.52 (1 H, d, J 16, 7-H) and 9.83 (1 H, d, J 7.5, CHO) (Found: m/z 294.148.C16H,,05 requires M, 294.146). Preparation of the C,-Phosphonium Chloride 32.-A solution of lithium chloride (0.41 g, 9.6 mmol) in dry DMF (3 cm3) was added to a stirred mixture of the formyl alcohol 31 (1.20 g, 9.5 mmol) and 2,4,6-trimethylpyridine (y-collidine) (1.4 cm3, 10 mmol) at 0 "C and the mixture was stirred for 10 min. To this reaction mixture, was added methanesulfonyl chloride (MsCI) (0.81 cm3, 10 mmol) and stirring continued at 0 "C for a further 1 h. The mixture was poured into ice-water and extracted with ether. The organic layer was washed with aqueous 3% HCI, saturated aqueous NaHCO, and brine.Evaporation of the dried extract provided a residue which was purified by short CC (ether-hexane, 2 :3) to afford the corresponding chloride (1.19 g). Subsequently, triphenylphosphine (2.05 g, 7.8 mmol) was added to a solution of the chloride (1.19 g, 7.4 mmol) in CH,CI, (60 cm3) and the mixture was refluxed for 22 h. Evaporation of the solvent gave a residue which was washed with ether to provide the phosphonium chloride 32 (2.23 g, 55%) as a pale yellow solid; A,,,(EtOH)/nm 225 and 275; v,,,/cm-' 1680 (conj. CHO). diluted with ether, washed with brine and evaporated. The residue was purified by short CC (acetone-hexane, 1 :3) and then pHPLC [LiChrosorb Si 60(5 pm) 1.0 x 30 cm; THF- hexane, 3 :71 to provide the sulfone 28 (272 mg, 63% from 26) as a yellow foam.(b) From the 1lZ-apocarotenal 29. In the same manner as described above, 29 (135 mg) provided the all-E-sulfone 28 (103 mg, 51%)through the diacetate 30 [1,,,(EtOH)/nm 3 13sh, 327, 342 and 361; v,,,/cm-' 3600 and 3420 (OH), 1930 (C===C==C)and 1725 (OAc)]. (c) From the CIS-allenic aldehyde 23. A mixture of the Czz- apocarotenals 26 and 29 prepared from 23 (320 mg) was treated in a manner similar to that used for the preparation of 28 from 26 to provide the all-E-sulfone 28 (244 mg, 51% from 23); L,,,(EtOH)/nm 321sh, 336, 353 and 372; v,,,/cm-' 3590 and 3470 (OH), 1930 (C====),1728 (OAc), 1305 and 1295 (split) (SO,) and 1140 (SO,); dH(500 MHz) 1.10 (3 H, S, 1-Me), 1.37 and 1.41 (each 3 H, s, 1-Me and 5-Me), 1.81 (3 H, s, 9-Me), 1.92 (3 H, s, 15'-Me), 2.08 (3 H, s, OAc), 3.84 (2 H, s, 14'-H2), 5.42 (1 H, m, 3-H), 5.76 (1 H, d, J 11, 15-H), 6.06 (1 H, s, 8-H), 6.08 (1 H,d, J12, 10-H),6.16(1 H,dd, J14.5, 12, 13-H),6.30(1 H,dd, J14.5, 12, 12-H),6.36(1 H,dd, J14.5, 11, 14-H),6.53(1 H,dd, J14.5, 12, ll-H),7.58(2H, t, J8,ArH), 7.68(1 H, t, J8,ArH) J.CHEM. SOC. PERKIN TRANS. 1 1993 and 7.89 (2 H, t, J 8, ArH) (Found: m/z 510.241. C30H3805S requires M, 510.244). (2E/Z,4E)-5-(4-Acetoxy-2,6,6-trimethylcyclohex-1-enyl)-3-rnethoxycarbonylpenta-2,4-dienal16 and 18.-In the same manner as described for the preparation of 15and 17 from 13, the ally1 ester 14 '(500 mg) provided an isomeric mixture of the formyl esters which was purified by low pressure column chromatography (ether-hexane, 1 :4) to yield the 9E-isomer 16 (80 mg, 23%) and the 9Z-isomer 18 (74 mg, 21%), as yellow oils, respectively. Compound 16:A,,,(EtOH)/nm 233 (E 8600), 273sh (E 6000) and 325sh (E 3600); vmax/cm-l 1725 (OAc and CO,Me), 1670 (conj.CHO) and 1605 (EX);dH(200 MHz) 1.1 1 and 1.15 (each 3 H, s, gem-Me), 1.60 (1 H, t, J 12,2ax-H), 1.80 (3 H, s, 5-Me), 1.81 (1 H, ddd, J12,4, 2, 2eq-H), 2.06(3 H, s, OAc), 2.14 (lH,brdd,J17.5,9,4ax-H),2.51(1H,brdd,J17.5,6,4eq-H), 3.87(3 H,s,CO,Me),4.06(1 H,m, 3-H),6.57(1 H, brd, J16,7- H),6.66(1 H,d, J7, 10-H),6.66(1 H,d, J16,8-H)and 10.06(1 H,d,J7,CHO)(Found:m/z321.170.C,,H,505requiresM+ H, 321.170). Compound 18: A,,,(EtOH)/nm 267 (E 10400) and 325 (E 11400); v,,,/cm-' 1725 (OAc and CO,Me), 1670 (conj.CHO) and 1605 (W);dH(200 MHz) 1.09 and 1.13 (each 3 H, s, gem-Me), 1.59 (1 H, t, J 12, 2ax-H), 1.76 (3 H, s, 5-Me), 1.79 (1 H, ddd, J 12, 4, 2, 2eq-H), 2.05 (3 H, s, OAc), 2.12 (1 H, br dd, J 17.5,9,4ax-H), 2.49 (1 H, br dd, J 17.5,6,4eq-H), 3.94 (3 H, s, CO,Me), 4.03 (1 H, m, 3-H), 6.09 (1 H, d, J7.5, 10-H), 6.21 (1 H, d, J 16, 8-H), 6.62 (1 H, br d, J 16, 7-H) and 9.78 (1 H, d, J 7.5, CHO) (Found: m/z 321.169. Cl8HZ5O5 requires M + H, 321.170). Isomerization of the 9E-Formyl Ester 16.411 the same manner as described for isomerization of 15, the 9E-formyl ester 16 (282 mg) was treated with iodine to provide 16(107 mg, 38%) and 18 (106 mg, 38%). Condensation of the Formyl Ester 18 and the Allenic SuIfone 28.-A solution of BuLi (1.59 mol dm-3 in hexane; 0.53 cm3, 0.84 mmol) was added to a stirred solution of diisopropylamine (0.12 cm3, 0.84 mmol) in dry THF (1.5 cm3) and hexane (1.5 cm3) at -78 "C and the mixture was stirred for a further 20 min.To this LDA solution, was added a solution of the sulfone 28 (216 mg, 0.42 mmol) in dry THF (2.5 cm3) and hexane (2.5 cm3). After the mixture had been stirred for 20 min at -78 "C, a solution of the formyl ester 18(90 mg, 0.28 mmol) in dry THF (2.5 cm3) and hexane (2.5 cm3) was added at the same temperature. The reaction mixture was stirred at -78 OC for 10 min before being allowed to warm to room temperature over ca. 20 min with stirring. After being quenched with saturated aqueous NH4Cl, the mixture was extracted with ether.The extracts were washed with brine, dried and evaporated to give a residue which was purified by CC (acetone-hexane, 1 :4) and then pTLC (acetone-hexane, 7: 13) to afford an isomeric mixture (33:34 = ca. 6: 1) (36 mg, 20% from 18). pHPLC separation [LiChrosorb Si 60(5 pm) 0.75 x 30 cm; AcOEt- cyclohexane-benzene, 2 :4 :4) of the mixture provided the 1 1 '2-isomer 33 and the 1 1'E-isomer 34,as red glasses, respectively. Compound 33: A,,,(EtOH)/nm 475; A,,,(hexane)/nm 435sh, 461 and 491; v,,,/cm 3590 and 3440 (OH), 1927 (EX==), 1745sh and 1725 (OAc and EX);dH(500 MHz) 1.06 and 1.35 (each 3 H, s, 1-gem-Me), 1.1 1 and 1.13 (each 3 H, s, 1'-gem-Me), 1.38 (3 H, s, 5-Me), 1.76 (3 H, s, 5'-Me), 1.80 (3 H, s, 9-Me), 2.03 and 2.05 (each 3 H, s, OAc x 2), 2.23 (3 H, s, 13'-Me), 5.05 (1 H, m, 3'-H), 5.38 (1 H, tt, J 11.5,4.4, 3-H), 5.71 (1 H, s, 12'-H), 6.05 (1 H, S, 8-H), 6.11 (1 H, d, J 11.5, 10-H), 6.20 (1 H, d, J 16.4, 8'-H), 6.38 (1 H, dd, J 14.4, 11.2, 12-H), 6.44 (1 H, d, J 11.5, 14'-H), 6.50 (1 H, dd, J 14.2, 11.2, 15-H), 6.60 (1 H, dd, J 1607 10'-H) and 7.22 (1 H, d, J 16.4, 7'-H) (Found: m/z 656.370.C41H5207 requires M, 656.371). Compound 34:A,,,(EtOH)/nm 480; A,,,(hexane)/nm 435sh, 465 and 491; v,,,/cm-' 3590 and 3440 (OH), 1925 (G==)and 1745sh and 1725 (OAc and EX);dH(500 MHz) 1.05 and 1.33 (each 3 H, s, 1-gem-Me), 1.1 1 and 1.13 (each 3 H, s, 1'-gem-Me), 1.37 (3 H, s, 5-Me), 1.76 (3 H, s, 5'-Me), 1.80 (3 H, s, 9-Me), 2.02 and 2.04 (each 3 H, s, OAc x 2), 2.10 (3 H, s, 13'-Me), 5.04 (1 H, m, 3'-H), 5.36 (1 H, tt, J 12.1, 4.2, 3-H), 6.03 (1 H, s, 8-H), 6.09 (1 H, d, J 11.7, 10-H), 6.22 (1 H, d, J 16.2,8'-H), 6.37 (1 H, dd, J14.2, 11.0, 12-H),6.37(1 H,s, 12'-H),6.42(1 H,d, J11.7, 14'-H), 6.51 (1 H, dd, J 14.2, 11.0, 15-H), 6.59 (1 H, dd, J 14.2, 11.7, 11-H), 6.61 (I H, dd, J 14.2, 11.7, 15'-H), 7.31 (1 H, d, J 16.2, 7'-H) and 7.41 (1 H, s, 10'-H) (Found: m/z 656.371.C~lH5207 requires M, 656.371). Epoxidation of the 9Z-Formyl Ester 18.--In the same manner as described for MCPBA-oxidation of 17, the formyl ester 18 (335 mg) was treated with MCPBA to give oxidation products, which were purified by pHPLC [LiChrosorb Si 60(5 pm) 1.O x 30 cm; ether-hexane, 35 :65) to provide the syn-epoxide 20 (164 mg, 47%) and the anti-epoxide 22 (70 mg, 2073, as pale yellow oils, respectively. Compound 20: A,,,(EtOH)/nm 282; v,,,/cm-' 1730 (OAc and C02Me), 1677 (conj. CHO) and 1625 (W);dH(200 MHz) 1.OO, 1.19 and 1.23 (each 3 H, s, gem-Me and5-Me),1.36(1H,ddd,J12.5,4.5,1.5,2eq-H),1.65(1H,t,J 12.5,2ax-H),1.87(1H,dd,J15,9.5,4ax-H),2.02(3H,s,OAc), 2.33 (1 H,ddd, J15,7.5,1.5,4eq-H), 3.94(3 H, s, CO,Me), 4.90 (1H,m,3-H),6.15(1H,d,J7.5,10-H),6.36(1H,d,J16,8-H), 6.46 (1 H, d, J 16, 7-H) and 9.85 (1 H, d, J7.5, CHO) (Found: m/z 336.158.C18H2406 requires M, 336.157). Compound 22: A,,,(EtOH)/nm 282; vmax/cm-l 1730 (OAc and CO,Me), 1677, (conj. CHO) and 1623 (W);dH(200 MHz) 1.00, 1.18 and 1.21 (each 3 H, s, gem-Me and 5-Me), 1.37 (1 H, dd, J 13.5,9,2ax-H), 1.67 (1 H, ddd, J 13.5,3.5, 1,2eq-H), 1.78 (1 H, dd, J 15,8,4ax-H), 2.02 (3 H, s, OAc), 2.42 (1 H, ddd, J 15, 5.5,1,4eq-H),3.94(3H,s,CO,Me),4.93(1H,m,3-H),6.15(1 H, d, J7.5, 10-H), 6.40(1 H, d, J16,8-H), 6.52(1 H, d, J 16,7-H) and 9.84 (1 H, d, J 7.5, CHO) (Found: m/z 336.156.C, ,H,,06 requires M, 336.157). Preparation of ( f)-Peridinin Acetate 35.-According to the procedure described for the condensation between 18 and 28, the anti-epoxide 22 (100 mg, 0.30 mmol) was treated with the allenic sulfone 28 (242 mg, 0.47 mmol) to give crude products, which were purified by short CC (acetone-hexane, 7: 13) and then pHPLC [LiChrosorb CN(7 pm) 0.7 x 25 cm; AcOEt- hexane, 3 :17) to afford peridinin acetate 35 (26 mg, 13% from 22) as a red glass.Spectral properties of synthetic 35* were identical with those of a semi-synthetic sample prepared from the authentic peridinin? A,,,(EtOH)/nm 473; A,,,(hexane)/nm 430sh, 456 and 486; ~,,,/cn-~ 3690 and 3595 (OH), 1925 (EX==)and 1740 (OAc and M);dH(500 MHz) (0.99 and 1.23(each 3 H, s, 1'-gem-Me), 1.07 and 1.35 (each 3 H, s, 1-gem-Me), 1.20 (3 H, s, 5'-Me), 1.39 (3 H, s, 5-Me), ca. 1.40 (2'ax-H + 2ax-H), 1.66 (1 H, dd, J 13.5, 3,2'eq-H), 1.79 (1 H, dd, J 15, 7, 4'ax-H), 1.80 (3 H, s, 9-Me), 2.00 (1 H, ddd, J 12.5,4,2,2eq-H), 2.03 and 2.04 (each 3 H, s, OAc x 2), 2.23 (3 H, s, 13'-Me), 2.29 (1 H, ddd, J 13,4, 2,4eq-H), 2.41 (1 H, dd, J 15, 5.5, 4'eq-H), 4.94 (1 H, m, 3'-H), 5.38 (1 H, tt, J 11.5, 4, 3-H), 5.74 (1 H, s, 12'-H), 6.05 (1 H, S, 8-H), 6.11 (1 H, d, J 12, 10-H), 6.38 (1 H, dd, J 14.5, 11, 12-H), 6.40 (1 H, d, J 15.5, 8'-H), 6.45 (1 H, d, J * This seems to be a mixture of diastereoisomers.t This was kindly supplied by Dr. Y. Tanaka, Kagoshima University, Japan. A mixed HPLC of the synthetic and the natural pigment showed 14.4,11.5,1l-H),6.61(1H,dd,J14.2,11.5,15'-H),7.03(1H,~,no spearation. 11.5, 14'-H),6.51 (1 H,dd, J14.5, 11, 15-H),6.61 (2H,brt-like, J 14, 11-H + 15'-H), 7.03 (1 H, s, 10'-H) and 7.19 (1 H, d, J 15.5, 7'-H) (Found: m/z 672.366. C~,HS,O~ requires M, 67 2.3 66). Preparation of ( k )-Peridinin 1.-According to the procedure described for the condensation of 18and 28, the anti-epoxide 21 (142 mg, 0.48 mmol) was treated with the allenic sulfone 28 (365 mg, 0.72 mmol) to give crude products, which were purified by short CC (acetone-hexane, 7: 13) and then pTLC (acetone- hexane, 9 : 11) to afford a condensed isomeric mixture (54 mg, 18% from 21) as a red glass.pHPLC separation [LiChrosorb CN(7 pm) 0.7 x 25 cm; MeOH-acetone-hexane, 1 :30: 1701 of the mixture provided the 11'2-isomer (peridinin) 1(8.7 mg) and the 11'E-isomer 36 (8.5 mg). Spectral properties of synthetic peridinin* were in good agreement with those of natural speci- rnen;tv2, Compound 1: A,,,(EtOH)/nm 472; R,,,(hexane)/nm 431sh, 456 and 485; v,,,/cm-' 3600 and 3450 (OH), 1928 (C====)and 1742 (GO);dH(500 MHz) 0.97, 1-20 and 1.21 (each 3 H, s, 1'-gem-Me and 5'-Me), 1.07 and 1.35 (each 3 H, s, 1-gem-Me), 1.26 (1 H, dd, J 12.5, 10.5, 2'ax-H), 1.38 (3 H, s, 5-Me), 1.38 (1 H, dd, J 12, 6, 2ax-H), 1.50 (1 H, t-like, J 13,4ax-H), 1.63(1 H, brd-like, J12.5,2'eq-H), 1.64(1 H,dd, J14.5,9, 4'ax-H), 1.SO (3 H, s, 9-Me), 1.99 (1 H, ddd, J 12,4, 2,2eq-H), 2.04 (3 H, s, OAc), 2.23 (3 H, s, 13'-Me), 2.28 (1 H, ddd, J 13,4, 2,4eq-H), 2.40 (1 H, ddd, J 14.5,4, 1.5,4'eq-H), 3.90 (1 H, m, 3'-H), 5.38 (1 H, tt, J 12,4, 3-H), 5.73 (1 H, S, 12'-H), 6.05 (1 H, ~,8-H),6.11 (1 H,d, J12, 1O-H),6.37(1 H,d, J15.5,8'-H),6.38 (1 H, dd, J 14, 11, 12-H), 6.45 (1 H, d, J 12, 14'-H), 6.51 (1 H, dd, J 14, 11, 15-H), 6.61 (2 H, dd, J 14, 12, 11-H + 15'-H), 7.02 (1 H, s, 10'-H) and 7.17 (1 H, d, J 15.5, 7'-H) (Found: m/z 630.354.C3,H&, requires M, 630.355).Compound 36:A,,,(EtOH)/nm 475; R,,,(hexane)/nm 431sh, 456 and 484; v,,,/cm-' 3600 and 3450 (OH), 1928 (G==C==C)and 1742 (m);dH(500 MHz) 0.96 (3 H, s, 1'-Me), 1.06 and 1.34 (each 3 H, s, 1-gem-Me), 1.19 (6 H, s, 1'-Me + 5'-Me), 1.25 (1 H, dd, J 12, 10,2'ax-H), 1.37 (3 H, s, 5-Me), 1.37 (1 H, dd, J 11, 7,2ax-H), 1.49 (1 H, t-like, J 12.5,4ax-H), 1.62 (1 H, br d-like, J 12,2'eq-H), 1.63 ( 1 H, dd, J 14.5,9,4'ax-H), I .79 (3 H, s, 9-Me), 1.98(1 H, ddd, J 11,4,2,2eq-H), 2.03 (3 H, s, OAc), 2.09(3 H, s, 13'-Me), 2.27 (1 H, ddd, J 12.5, 4, 2,4eq-H), 2.38 (1 H, ddd, J 14.5,4, 1.5,4'eq-H), 3.89 (1 H, m, 3'-H), 5.37 (1 H, tt, J 11,4, 3- J. CHEM. soc. PERKIN TRANS. 1 1993 s,14'-H2),5.03(1H,m,3-H),5.71(1H,brd,J11.5,15-H),6.14 (1 H, dd, J 14.5, 11.5, 13-H), 6.28 (1 H, dd, J 14, 11.5, 12-H), 6.35 (1 H, dd, J 14.5, 11.5, 14-H), 6.38 (1 H, dd-like, J 11.5, 1.5, 10-H), 6.46 (1 H, dd, J 14, 11.5, 11-H), 7.54 (2 H, t-like, J 8, ArH), 7.64 (1 H, tt, J 8, 1.5, ArH), and 7.84 (2 H, d-like, J 8, ArH) (Found: m/z 492.231.C,,H,,O,S requires M, 492.233). Compound 40:R,,,(EtOH)/nm 266sh, 275, 348sh, 363 and 382; v,,,/cm-' 2170 (CK), 1730 (OAc), 1310 and 1300 (split) (so,)and 1 142 (SO,); dH(200 MHz) 1.21 and 1.23 (each 3 H, s, gem-Me), 1.59 (1 H, t, J 12, 2ax-H), 1.86 (1 H, ddd, J 12, 4, 2, 2eq-H), 1.87, 1.94 and 1.99 (each 3 H, s, 5-Me, 9-Me and 15'- Me), 2.06 (3 H, s, OAc), 2.16 (1 H, br dd, J 18, 10,4ax-H), 2.53 (1 H, br dd, J 18,6,4eq-H), 3.80 (2 H, s, 14'-H2), 5.05 (1 H, m, 3-H), 5.74(1 H, d, J 11, 15-H), 6.11 (1 H, dd, J 14, 11, 13-H), 6.23 (1 H, d, J 11, 10-H), 6.27 (1 H, dd, J 14, 11, 12-H), 6.35 (1 H, dd, J 14, 11, 14-H), 6.71 (1 H, dd, J 14, 11, 11-H), 7.54 (2 H, t-like, J 7, ArH), 7.65 (1 H, tt, J 7, 2.5, ArH) and 7.86 (2 H, d- like, J 7, ArH) (Found: m/z 492.232.C30H3604S requires M, 492.23 3). Preparation of ( k )-Pyrrhoxanthin 2.-According to the procedure as described for the condensation between 18 and 28, the anti-epoxide 21 (146 mg, 0.50 mmol) was treated with the acetylenic sulfone 39 (393 mg, 0.80 mmol) using diisopro- pylamine (0.13 cm3, 0.93 mmol) and BuLi (I .49 mol dmP3 in hexane; 0.63 cm3, 0.93 mmol) to give crude products, which were purified by short CC (acetone-hexane, 1:3) and then pTLC (MeOH-CH,Cl,, 3 :97) to afford a condensed isomeric mixture (41 mg, 13% from 21) as a red glass.pHPLC separation [LiChrosorb CN(7 pm) 0.7 x 25 cm; acetone-hexane, 12:881 of the mixture provided the 1 1 '2-one (pyrrhoxanthin) 2 (1 8 mg) and the 1 1'E-isomer 41 (15 mg). Spectral properties of the synthetic pyrrhoxanthin* were in accordance with those rep~rted.~Compound 2: A,,,(EtOH)/nm 466; A,,,(hexane)/nm 437sh, 459 and 487; v,,,/cm-' 3600 and 3570 (OH), 2160 (CS) and 1745 (C=O);dH(5OO MHz) 0.94 (3 H, S, 1'-Me), 1.14 (3 H, S, 1-Me), 1.16(6H, s, 1-Me + 5'-Me), 1.17(3 H, s, 1'-Me), 1.22(1 H, dd, J 12.5, 10, 2'ax-H), 1.53 (2ax-H), 1.60 (1 H, br d-like, J 12.5, 2'eq-H), 1.60 (1 H, dd, J 14.5,9,4'ax-H), 1-80 (1 H, ddd, J 12.5, 3, 1.5, 2eq-H), 1.87 (3 H, s, 5-Me), 1.96 (3 H, s, 9-Me), 2.06 (3 H, s, OAc), 2.10 (1 H, dd, J 17, 9, 4ax-H), 2.19 (3 H, s, 13'-Me), 2.36 (1 H, ddd, J 14.5,5, 1.5,4'eq-H), 2.46 (1 H, br dd, H),6.04(1 H,~,8-H),6.lO(lH,d,J11.5,10-H),6.36(1H,dd,JJ 17, 5,4eq-H), 3.87 (1 H, m, 3'-H), 5.00 (1 H, m, 3-H), 5.70 (1 14.5, 11, 12-H), 6.39 (1 H, S, 12'-H), 6.40 (1 H, d, J 15.5, 8'-H), 6.43 (1 H, d, J 11.5, 14'-H), 6.52 (1 H, dd, J 14.5, 11, 15-H), 6.59 (1 H, dd, J 14.5, 11.5, 11-H),6.62(1 H, dd, J14.5, 11.5, 15'-H), 7.24 (1 H, d, J 15.5, 7'-H) and 7.43 (1 H, s, 10'-H) (Found: m/z 630.355.C&&, requires M, 630.355). Synthesis of Racemic Pyrrhoxanthin 2 (3E/Z,5E,7E,9E)-(k )-4-(3,1O-Dimethyl-1 1 -phenylsulfonyl-undeca-3,5,7,9-tetraen-1-ynyl)-3,5,5-trimethylcyclohex-3-enyl Acetate 39 and 40.-Following the procedure as described for the preparation of the allenic sulfone 28 from the apocarotenal 26, the all-E-acetylenic apocarotenal37 l5 (845 mg, 2.6 mmol) gave an isomeric mixture of sulfones which was purified by short CC (ether-hexane, 1 : 1) and then pHPLC [LiChrosorb Si 60(7 pm) 2.5 x 25 cm; ether-hexane, 2: 31 to provide the all-E- isomer 39 (398 mg, 31%) and 92-one 40 (396 mg, 31%), as yellow foams, respectively.Compound 39: A,,,(EtOH)/nm 350sh, 366 and 386; v,,,/cm-' 2270 (CK), 1728 (OAc), 1310 and 1300 (split) (SO,) and 1142 (SO,); 6,(500 MHz) 1.17 and 1.19 (each 3 H, s, gem-Me), 1.56 (1 H, t, J 12,2ax-H), 1.83 (1 H, ddd, J 12,4,2,2eq-H), 1.88 and 1.90 (each 3 H, s, 5-Me and 15'- Me), 1.97 (3 H, s, 9-Me), 2.04 (3 H, s, OAc), 2.13 (1 H, br dd, J 17.5,9.5,4ax-H),2.49(1 H, brdd, J17.5,5.5,4eq-H), 3.80(2H, H, S, 12'-H), 6.34 (1 H, d, J 15.5, 8'-H), 6.36 (1 H, dd, J 14.5, 11.5, 12-H), 6.40 and 6.41 (each 1 H, d, J 11.5, 10-H and 14'-H), 6.46(1H,dd,14,11.5, 15-H),6.54(1 H,dd,J14.5,11.5, 11-H), 6.60(1 H,dd, J14, 11.5, 15'-H),6.98(1 H,s, 10'-H)and7.14(1 H, d, J 15.5,7'-H) (Found: m/z 612.344. C39H4806 requires M, 612.345).Compound 41: A,,,(EtOH)/nm 473; A,,,(hexane)/nm 437sh, 458 and 488; v,,,/cm-' 3600 and 3480 (OH), 2160 (Cg) and 1745 (GO);d,(500 MHz) 0.98 (3 H, s, 1'-Me), 1.18 (3 H, s, 1-Me), 1.20(6H, s, 1-Me + 5'-Me), 1.21 (3 H, s, 1'-Me), 1.26(1 H, dd, J 12.5, 10.5, 2'ax-H), 1.57 (2ax-H), 1.64 (2'eq-H), 1.64 (1 H, dd, J 14.5, 9, 4'ax-H), 1.84 (1 H, ddd, J 12.5, 4, 2, 2eq-H), 1.91 (3 H, s, 5-Me), 2.01 (3 H, s, 9-Me), 2.05 (3 H, s, OAc), 2.10 (3H,s,13'-Me),2.14(1H,dd,J17,9,4ax-H),2.40(1H,ddd,J 14.5,5,1.5,4'eq-H),2.50(1H,brdd,J17,5,4eq-H),3.91(1H, m, 3'-H), 5.04(1 H,m, 3-H), 6.41 (1 H, s, 12'-H), 6.42(1 H, d, J 15.5, 8'-H), 6.45 (2 H, d-like, J 11.5, 10-H + 14'-H), 6.52 (1 H, dd, 14, 11, 15-H),6.60(1 H,dd, J14.5, 11.5, 11-H), 6.63 (1 H, dd, J 14.5, 11.5, 15'-H), 7.26 (1 H, d, J 15.5, 7'-H) and 7.45 (1 H, s, 10'-H) (Found: m/z 612.341.C,,H4,06 requires M, 612.345). **tSee preceding page. 1609J. CHEM. soc. PERKIN TRANS. I 1993 Synthesis of Optically Active Peridinin 1 Preparation of the Optically Active Compounds 6. 7 and 8.-According to the preparation of the racemic compounds, optically active compounds 6, 7 and 8 were prepared.6: [a];' -69.9 (c 2.94, MeOH). 7: [a];' -50.9 (c 1.93, MeOH). 8: [a]k3 -46.0 (C 1.28, MeOH). Conversion of the (3R)-Dienyl Ester 8into the Camphanate 42 and Determination of its Optical Purity.-Following the procedure given for 13, treatment of (3R)-8 (1 11 mg) with TBAF followed by purification by short CC (acetone-hexane, 1 :3) afforded the 3-hydroxy compound (65 mg, 88%). To a mixture of this compound (65 mg, 0.29 mmol), triethylamine (0.12 cm3, 0.86 mmol) and DMAP (72 mg, 0.59 mmol), was added (-)-camphanic acid chloride (CpCI) (192 mg, 0.89 mmol) at 0 "C. The reaction mixture was stirred at 0 "C for 30 min, poured into ice-water and extracted with CH2C12.The extracts were washed with brine, dried and evaporated. The residue was purified by short CC (ether-hexane, 2 :3) to afford the camphanate 42 (1 14 mg, 97%). The optical purity of 42 was 88% e.e. based on HPLC analysis [LiChrosorb Si 60(5 pm) 0.4 x 30 cm; AcOEt-cyclohexane, 7 :93; 1.2 cm3min-'; 280 nm detect.]. ~,,,(EtOH)/nm 275; vmax/cm-' 1780 (GO), 1715 (conj. C0,Me) and 1630 (M);6H(200 MHz) 0.98 and 1.07 (each 3 H, s, Cp-gem-Me), 1.12 (6 H, s, Cp-Me + 1-Me), 1.17 (3 H, s, 1-Me), 1.77 (3 H, s, 5-Me), 3.78 (3 H, s, CO,Me), 5.83 (1 H, d, J 16, 8-H) and 7.36 (1 H, br d, J 16, 7-H) (Found: m/z 404.218. C23H320, requires M, 404.220). Preparation of the Optically Active Compounds 9-13, 15, 17, 19 and 21.-According to the preparation of the racemic compounds, optically active compounds 9-13,15,17,19 and 21 were prepared.9:[a];, -63.0 (c 1.28, MeOH). 10: Cali3 -55.2 (c 1.14, MeOH). 11: [a];, -41.1 (c 1.07, MeOH).12: Cali3 -41.4 (c 0.99, MeOH). 13: [a]i3-54.6 (c 1.41, MeOH). 15: [a];' -57.8 (c 0.21, MeOH). 17: [a];, -58.4 (c 0.43, MeOH). 19: [a]h4 +26.7 (c 0.86, MeOH). 21: [a];' -77.0 (c 0.79, MeOH). [1R,4S/R,5R-(E)]-4-(5-Acetoxy-3-methylpent-3-en-1-ynyl)-4-hydroxy-3,3,5-trimethylcyclohexylAcetate 45 and 46.-TMSCl (22.5 cm', 177 mmol) was added dropwise to a stirred solution of the (4R,6R)-hydroxy ketone 5" (25.00 g, 160 mmol) and triethylamine (20.0 g, 198 mmol) in dry ether (250 cm3) at 0 "C and the mixture was stirred at room temperature for 7 h.The mixture was filtered to remove the salt and the filtrate was washed with brine. Evaporation of the dried solution followed by distillation (80-83 "C/0.03 mmHg) gave the TMS ether 43 (33.83 g, 93%) as a colourless oil; vm,Jcm-' 1700(C==0);6,(60MHz)O.l3(9H,s,SiMex 3), 1.00(3H,d,J 7, 6-Me), 1.01 and 1.32 (each 3 H, s, gem-Me), 3.17 (1 H, m, 6- H) and 4.08 (1 H, quint, J 3, 4-H). BuLi (1.62 mol dmP3 in hexane; 106 cm', 171 mmol) was added dropwise to a solution of TMS ether of (E)-3-methylpent-2-en-4-yn-l-o1(30.79g, 171 mmol) in ether (1 50 cm3) at 0 "C. To this mixture, was added dropwise a solution of (4R,6R)-43 (30.00 g, 132 mmol) in ether (1 50 cm') at 0 "C and the reaction mixture was stirred for 1.5h at room temperature.After the reaction had been quenched with saturated aqueous NH,Cl, the mixture was extracted with ether. The extracts were washed with brine, dried and evaporated to give the crude hydroxy compound 44 which, without purification, was dissolved in MeOH (450 cm3) and p-TsOH (450 mg) was added to it. After being stirred for 1 h at room temperature, the mixture was diluted with AcOEt and the organic layer was washed with saturated aqueous NaHCO, and brine. Evaporation of the dried solution gave the triol which, without purification, was dissolved in Py (300 cm3) and acetic anhydride (120 an3)was added to it. The mixture was stirred at room temperature for 16 h, poured into ice-water and extracted with ether. The extracts were washed successively with aqueous 5% HCl, saturated aqueous NaHCO, and brine.Evaporation of the dried extracts gave a residue which was purified by CC (ether-hexane, 1 :1) to afford a mixture of (3R)-45 and (3R)-46 [7:1 based on HPLC analysis: 36.39 g, 82% from (4R,6R)-5). It was recrystallized from ether-hexane to give the pure (3R)-45 C32.17 g, 73% from (4R,6R)-5] as colourless crystals (m.p. 76-79 "C). pHPLC separation [LiChrosorb Si 60(7 pm)1.0 x 25 cm; ether-hexane, 1 :21 of a part of the evaporated filtrate gave the pure (3R)-46 as an oil. Compound 45: [#]if" -24.1 (c 0.99, MeOH); v,,,/cm-' 3600 and 3450 (OH) and 1730 (OAc); 6,(500 MHz) 1.07 (3 H, d, J 6.5, 5-Me), 1.10 (3 H, s, leq-Me), 1.14 (3 H, s, lax-Me), 1.64 (1 H, ddd, J 15, 13,3,4ax-H), 1.73 (2 H, m, 2-H,), 1.76 (1 H, br d, J 15,kq-H), 1.88 (3 H, dt, J 1.5,0.5,9-Me), 1.92 (1 H, s, OH), 2.04 and 2.07 (each 3 H, s, OAc x 2), 2.25 (1 H, dqd, J 13,6.5, 4,5-H), 4.64 (2 H, dd-like, J 7,0.5, 1 1 -H2), 4.95 (1 H, quint, J 3, 3-H), 5.90 (1 H, tq, J 7, 1.5, 10-H) (Found: m/z 336.194.C,gH2@5 requires M, 336.194) (Found: C, 67.8; H, 8.5. C1gH2805 requires C, 67.83; H, 8.39%). Compound 46:[a];' -13.5 (c 0.97, MeOH); vmaX/cm-' 3600 and 3450 (OH) and 1730 (OAc); 6,(500 MHz) 1.06 (3 H, s, leq-Me), 1.10 (3 H, d, J6.5, 5-Me), 1.20 (3 H, s, lax-Me), 1.57-1.62 (2 H, m, 4eq-H + 2eq-H), 1.68 (1 H, ddd, J 15, 13, 3, 4ax-H), 1.74(1 H, s, OH), 1.77 (1 H, dd, J 15,3,2ax-H), 1.87 (3 H, m, 9- Me), 2.03 and 2.07 (each 3 H, s, OAc x 2), 2.24 (1 H, dqd, J 13, 6.5,4,5-H),4.64(2H,dd-like,J7,0.5, 11-H,), 5.00(1 H,quint, J 3, 3-H), 5.90 (1 H, tq, J7, 1.5, 10-H) (Found: m/z 336.194.C19H2805requires M, 336.194). [1R-(E)]-4-(5-Acetoxy-3-methylpent-3-en-1-ynyl)-3,5,5-trimethylcyclochex-3-enylAcetate 47.-Phosphorus oxychlo-ride (15 an3)was added slowly to a stirred solution of (3R)-45 (17.50 g, 52 mmol) in Py (1 00 cm3) and the mixture was stirred at 75 "C for 15 h. After cooling, the reaction mixture was cautiously poured into ice-water. The resultant mixture was neutralized with NaHCO, and extracted with ether. The extracts were washed successively with aqueous 5% HCl, satur- ated aqueous NaHCO, and brine. Evaporation of the dried solution gave a residue which was purified by CC (ether- hexane, 1 :1) to afford the enyne diacetate 47 (1 1.13 g, 67%) as a pale yellow oil.Spectral properties of this optically active 47 were identical with those of racemic one;', [a];3 -48.5 (c 1.03, MeOH). Preparation of Optically Active Epoxides 48 and 49.-In the same manner as described for MCPBA-oxidation of 17, the enyne diacetate 47 (16.0 g) was treated with MCPBA to give oxidation products, which were purified by low pressure column chromatography (ether-hexane, 3 :7) to provide the syn-epoxide 48 (4.56 g, 27%) and the anti-epoxide 49 (3.82 g, 23%), as pale yellow oils, respectively. Spectral properties of these optically active epoxides were identical with those of racemic analogues;" 48: [a];6 -45.7 (c 1.09, MeOH); 49: [a];' +4.8 (c 1.04, MeOH).{2R-[ 1R*(E),2a,4~]}-5-(2,4-Dihydroxy-2,6,6-trimethylcyclo-hexylidene)-3-methylpenta-2,4-dienaI 23.-A solution of DIBAL (4.96 g, 36 mmol) in dry CH2Cl, (100 cm3) was added dropwise to a stirred solution of the anti-epoxide 49 (2.00 g, 6 mmol) in dry CH,Cl, (100 cm3) at 0 "C. After the mixture had been stirred for a further 1 h, the excess of reagent was decomposed by dropwise addition of water. The mixture was saturated with NaCl and then thoroughly extracted with CH,Cl,. The extracts were washed with brine, dried and evaporated to give the crude allenic triol which, without purification, was dissolved in THF. The solution was shaken with active MnO, (12 g) at room temperature for 4 h. The mixture was filtered through Celite.Evaporation of the filtrate gave a residue, which was purified by short CC (acetone- hexane, 35 :65) to provide the allenic aldehyde 23 (1.26 g, 84%) as a pale yellow solid. Spectral properties of this optically active 23 were identical with those of racemic one;' [a]F -60.0 (c 1 .OO, MeOH). Conversion of the (3S)-Allenic Aldehyde 23 into the Camphanate 50 and Determination of its Optical Purity.-Py (1 cm3) and (-)-CpCl (37 mg, 0.17 mmol) was added to a stirred solution of the allenic aldehyde 23 (36 mg, 0.14 mmol) in dry CH2C12(2 cm3) at 0 "C. After being stirred at 0 "C for 30 min, the reaction mixture was diluted with ether. The organic layer was washed with aqueous 3% HCl, saturated aqueous NaHCO, and brine. Evaporation of the dried solution gave a residue which was purified by pTLC (acetone-hexane, 1 :2) to afford the camphanate 50 (47 mg, 76%).The optical purity of 50 was 96% e.e. based on HPLC analysis [LiChrosorb Si 60(5 pm) 0.4 x 30 cm; THF-hexane, 1 :4, 1.5 cm3 min-'; 300 nm detect.]; I,,,(EtOH)/nm 277; v,,,/crr-' 3600 and 3430 (OH), 1783(W),1725(GO),1935(G=G=C), 1655 (conj. CHO) and 1605 (W);6,(200 MHz) 0.98 and 1.07 (each 3 H, s, Cp-gem-Me), 1.13 (6 H, s, Cp-Me + 1-Me), 1.40 and 1.43 (each 3 H, s, 1-Me and 5-Me), 2.16 (3 H, d, J 1,9-Me), 5.96 (1 H, d, J8, 10- H),6.11(1 H,s,8-H)and10.05(1 H,d,J8,CHO)(Found:m/z 430.236. C25H340, requires M, 430.235). { 3 R -[1 f3,3~,4R *(3 E, 5E ,7 E,9 E)] -3-Hydro~y-4-( 3,lO- dimethyl-1 1 -phenylsulfonylundeca-1,3,5,7,9-~entaenylidene)-3,5,5-trimethylcyclohexyI Acetate 28.-According to the preparation of the racemic 28 from the racemic aldehyde 23,the optically active 28 was prepared; [a]E2 -13.7 (c 1.46, MeOH).Preparation of the Optically Active Peridinin 1.-According to the preparation of the racemic peridinin, the (3S)-formyl ester 21 was treated with the (3s)-allenic sulfone 28 to give the 11'2-isomer (peridinin) 1 and the 11'E-one 36. Spectral properties of these compounds were identical with those of racemic one. In addition, the CD spectrum of synthetic 1 was nearly superimposable on that reported by the Jensen group3 (see Fig. 1). 1 (Found: m/z 630.355. C39H5007 requires M, 630,356); 36 (Found: m/z 630.356. C3&,007 requires M, 630.356).Acknowledgements We wish to thank the Ministry of Education, Science and Culture (Japan) for a research grant and Dr. Y. Tanaka, Kagoshima University, and Professor S. Liaaen-Jensen, The Norwegian Institute of Technology, University of Trondheim, for their invaluable gift of natural specimens. We are also J. CHEM. SOC. PERKIN TRANS. 1 1993 indebted to Dr. K. Yamamoto and Mr. H. Adachi, Osaka University, for the high resolution MS measurements of the optically active 1 and 36.We thank Misses S. Ueda and H. Ito for technical assistance. References 1 (a)H. H. Strain, W. A. Svec, K. Aitzetmiiller, M. C. Grandolfo, J. J. Katz, H. Kjasen, S. Norgkd, S. Liaaen-Jensen, F. T. Haxo, P. Wegfahrt and H. Rapoport, J. Am. Chem. Soc., 1971,93,1823;(6)H. H.Strain, W. A. Svec, P. Wegfahrt, H. Rapoport, F. T. Haxo, S. Norgird, H. Kjasen and S. Liaaen-Jensen, Acta Chem. Scand., Sect. B, 1976,30, 109; (c) H. Kjasen, S. Norgird, S. Liaaen-Jensen, W. A. Svec, H. H. Strain, P. Wegfahrt, H. Rapoport and F. T. Haxo, Acta Chem. Scand., Sect. B, 1976,30, 157. 2 J. E. Johansen, W. A. Svec, S. Liaaen-Jensen and F. T. 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Hirata, K. Tsukida, N. Tanaka, K. Hamada, R. Hino and T. Fujiwara, Chem. Pharm. Bull., 1988,36, 3328. 16 K. Bernhard, F. Kienzle, H. Mayer and R. K. Mullar, Helv. Chim. Acta, 1980,63, 1473. 17 H. G. W. Leuenberger, W. Boguth, E. Widmer and R. Zell, Helv. Chim. Acta, 1976,59, 1832. 18 A. Baumeler and C. H. Eugster, Helv. Chim. Acta, 1991,74,469. 19 J. R. Hlubucek, J. Hora, S. W. Russell, T. P. Toube and B. C. L. Weedon, J. Chem. Soc., Perkin Trans. I, 1974,848. 20 (a)G. Englert, Pure Appl. Chem., 1985,57,801;(b) K. Bernhard, F. Kienzle, H. Mayer and R. K. Miiller, Helv. Chim. Acta, 1980, 63, 1473. 21 M. Acemoglu, P. Uebelhart, M. Rey and C. H. Eugster, Helv. Chim. Acta, 1988,71,931. 22 S. McLean and W. F. Reynolds, Magn. Reson. Chem., 1992,30,362. 23 A. J. Davies, A. Khare, A. K. Mallams, R. A. Massy-Westropp, G. P. Moss and B. C. L. Weedon, J. Chem. Soc., Perkin Trans. I, 1984, 2147. Paper 3/01450I Received 12th March 1993 Accepted 2nd April 1993
ISSN:1472-7781
DOI:10.1039/P19930001599
出版商:RSC
年代:1993
数据来源: RSC