Stereoselective Transformation of Ajmaline into Three Minor Gekemium Alkaloids, Koumidine, (192)-Anhydrovobasinediol [(192)-Taberpsychine] and N-Demethoxyrankinidine and their Absolute Configuration Mariko Kitajima, Hiromitsu Takayama and Shin-ichiro Sakai * Faculty of Pharmaceutical Sciences, Chiba University, 1-33, Yayoi-cho, Chiba 260, Japan Ajmaline was converted into new Gelsemiurn alkaloids, 19Z-anhydrovobasinediol [(19Z) -taberpsychine] and N-demethoxyrankinidine, via koumidine along the biomimetic sequence, and the absolute configuration of these alkaloids was determined by these transformations. The genus Gelsemiurn, belonging to the family Loganiaceae, comprises three species. Along them, Gelsemiurn efegans Benth., native to South Eastern Asia, has been used in traditional Chinese medicine, as well as a remedy for certain kinds of skin ulcers, and more recently has been used as an analgesic for the palliation of various acute cancer pains.Recent intensive research on the chemical components of these plants resulted in the isolation of many new indole and oxindole alkaloids., The structure of koumidine 3, one of the minor constituents of G. elegans, was first published as having an 19E ethylidene side- chain as in the common sarpagine class of indole alkaloids. By careful spectroscopic analysis, the configuration of the side-chain was revised to the 192 The structures of new minor alkaloids, (19Z)-anhydrovobasinediol [( 19Z)-taberpsychine] 2 2d and N-demethoxyrankinidine 1,2ewere also elucidated by spectroscopic analysis, but as yet their absolute configuration remains unsettled.Koumidine 3, 192-anhydrovobasinediol2, and N-demethoxyrankinidine 1may be biogenetically related in that the c/D-ring cleavage of koumidine 3 would generate compound 2 and subsequent oxidative rearrangement to oxindole would serve to generate compound We designed the synthesis of these alkaloids from the known compound ajmaline 46 along the above biomimetic sequence (Scheme 1). 19 1 2 19 3 4 Scheme 1 Initially, koumidine 3 was prepared from ajmaline 4. Our synthetic pathway contains (i) stereoselective introduction of a 2-olefin bond at C'9-C20 in ajmaline 4 and (ii) indoline-to- indole transformation without epimerization at C ".Ajmaline 4 was converted into the hydrazone derivative 5 in two steps (i, N,N-dimethylhydrazine and a catalytic amount of H2S04 in EtOH; ii, methyl chloroformate in 1 mol dm-3 NaOH- CH,Cl,) in 79% overall yield to liberate the masked aldehyde existing as an amino acetal function and to protect the Nb as the methyl~arbamate.~ The hydrazone was hydrolysed with copper(I1) chloride in aq. tetrahydrofuran (THF) (pH 7)* to afford the aldehyde 6 in 75% yield. In the 'H NMR spectrum, the signals due to the aldehyde group were observed at 6 9.62 and 9.59.y Attempts at direct conversion of ajmaline 4 into the aldehyde 6 by reaction with chloroformates gave solely the carbonate (2 1-OC0,R) derivatives. After the 17-hydroxy group in compound 6 had been protected as the methoxyethoxymethyl (MEM) ether 7 in 81% yield, the aldehyde was converted into the silyl enol ether 8 in 71% yield by treatment with t-butyldimethylsilyl trifluoromethanesulphonate (TBSOTf), and then bromine was selectively introduced into the a-position of the aldehyde in 76% yield by treatment with N-bromo- succinimide (NBS) in dry THF at -18 "C.To create the double bond at the C1'-C20 position, the bromide 9 was treated with 1,8-diazabicyclo[5,4,O]undec-7-ene (DBU) in dry dimethyl- formamide (DMF) to give two a,l)-unsaturated aldehydes, the desired 192-olefin 10 and 19E-olefin 11 in 60 and 12% yield, respectively. The geometry of two olefins was confirmed by NOE experiments. Irradiation of the 18-methyl protons (6 2.15,2.13) in Z-isomer 10 led to enhancement (1 7%) of the C-2 1 aldehyde proton (6 10.20, 10.19), while 25% enhancement was observed between the C-19 olefinic proton (6 6.56) and C-21 aldehyde proton (6 9.34, 9.32) in the E-isomer 11.The major a$-unsaturated aldehyde 10 was reduced with NaBH, to give the primary alcohol 12 in 88% yield. After deprotection of the Nb-carbamate by alkaline hydrolysis (NaOH in aq. ethylene glycol), the amine 14 was treated with mesyl chloride in dry pyridine to afford the ring-closure product 16 in 62% yield by bond formation between Nb and C-21. By removal of the MEM ether in compound 16, deoxyajmaline derivative 18 (map. 279- 281 "C) was obtained in 95% yield. By the same sequential treatment, the minor, 19E-olefin 11 gave the Rauwol$a alkaloid tetraphyllicine 19,9 m.p.294- 296 "C; "]b6 + 16" (c 0.4 in pyridine). Direct comparison of synthetic alkaloid 19 with an authentic sample established their identity in all respects (TLC, mixed m.p., IR, 'H NMR and mass spectra). The next requirement of this work was the transformation of the indolenine moiety to an indole ring. If we could prepare the indolenine derivative having a properly protected hydroxy group on C' 7, we could expect to obtain the indole derivative 24 by the fragmentation as shown in Scheme 2. First we protected the C-17 hydroxy group in compound 18 as the TBS ether 20 and prepared its indolenine derivative 22 by lead tetraacetate oxidation." After removal of the TBS group in compound 22 t Ajmaline derivatives possessing a carbamate function in the molecule are often shown by their 'H and 13CNMR spectra to occur as a mixture of rotation isomers.J. CHEM. SOC. PERKIN TRANS. 1 19914-Q$3/Q--43b+ Q--%OMEM A OMEM 20 Me / l9Me Me Me 'MeR2 R' CHO CH2OHR' Ff R3 21 ii 5 CH=N-NMe, H H 10 z 12 (19Z), R=C02Me hr t6CHO HH 11 E 14 (19Z), R=H >iX 13 (19 E), R = C02MeH MEM 15 (19€), R=H ix v -0TBS MEM '(9 CHO Br MEM lx 0 SiMe2R0-OR 19 24 n R=BU' 16 (192 ), R = MEMJ xi 23 R=Me 18 (lgZ), R=H 20 (1921, R = TBS )Vxvi or xvii 21 (192), R=TMS 17 (19€), R=MEM jXi 19 (19€), R=H R' R2 3 CH2OH H 25 H CH20H Scheme 2 Reagents: i, N,N-Dimethylhydrazine, cat. H,SO,, 3 A molecular sieves, dry EtOH; ii, methyl chloroformate, 1mol dm-3 NaOH, CH,Cl,; iii, CuCl,, aq.THF, phosphate buffer;iv, MEM chloride, diisopropylethylamine, dry CH,Cl,; v, TBSOTf, Et,N, dry CH,Cl,; vi, NBS, dry THF; vii, DBU, dry DMF; viii, NaBH,, MeOH; ix, NaOH, ethylene glycol, water; x, mesyl chloride, Py; xi, conc. HCl, MeOH; xii, TMSOTf, Et,N, dry CH,Cl,; xiii, Pb(OAc),, dry CH,Cl,; xiv, Bu,NF, THF; xv, AcOH-THF-water (3: 1:1); xvi, NaBH,, MeOH; xvii, NaBH,CN by use of tetrabutylammonium fluoride in THF at room type indole alkaloids by the use of osmium tetraoxide." In the temperature, the resulting aldehyde 24 was immediately re-case of the gardnerine series such as compound 27, which has a duced with NaBH, in MeOH to afford, however, 16-epi- methoxy group at C-6 of the indole ring, the oxidation with koumidine 25 [(19Z)-normacusine B, m.p.169-173 "C]as the OsO, proceeded predominantly on the C2-C7 bond (indole sole product. Strong nucleophilicity of the fluoride anion moiety) rather than on the C19-C20 (ethylidene side-chain).' presumably led to the epimerization at C16 in the aldehyde However, by the same procedure, the demethoxy indole 26 gave derivative 24. To prevent epimerization at CI6, the 17-hydroxy the oxindole diol 28 and the diol 29 in 38 and 37% yield, group of compound 18 was protected as the trimethylsilyl respectively. Attempts at regioselective oxidation by increasing (TMS) ether, which could be easily removed under mild the reactivity of the indole nuclear using the N" anion or Na-conditions, and then compound 21 was oxidized with Pb(OAc), trimethylsilyl derivative were ineffective.Furthermore, appli- in dry dichloromethane at -70 "C to -10 "C to give the cation of the general procedure, by using t-butyl hypochlorite,' unstable indolenine 23 in 63% overall yield from the alcohol 18. to compound 26 gave the undesired oxindole having the The indolenine 23 was successively treated with aq. AcOH- opposite configuration at C'. In turn, the indole 29 was THF at 0 "C and then with sodium cyanoborohydride to afford subjected to OsO, oxidation to give compound 28, identical koumidine 3, [a]L3 -23.5" (c 0.6 in MeOH), in 77% overall with the oxindole derived directly from compound 26. The yield from substrate 23. The 'H NMR, IR, UV, mass spectral oxindole thus obtained stereoselectively had the natural 7s and [alD data and m.p.were identical with those of natural configuration, as confirmed by a comparison of the CD koumidine. spectrum with that of humanthenine-type alkaloids." The 192 Koumidine 3 was treated with 2,2,2-trichloroethyl chloro- ethylidene double bond was regenerated by a three-step formate in aq. THF in the presence of a large excess of sequence.', Thus, diol 28 was treated with trimethyl ortho- magnesium oxide to give the carbamate 26 in 58% yield. The formate in the presence of pyridium toluene-p-sulphonate resulting carbamate 26 was reduced with lithium aluminium (PPTS) to give the corresponding 2-methoxy- 1,3-dioxolane7 hydride to afford the desired (19Z)-anhydrovobasinediol 2, which was refluxed in acetic anhydride and then the N"-acetyl [a]h3 -151" (c 0.3 in CHCI,), in 86% yield.The 'H NMR, IR, group was removed by alkaline hydrolysis to afford the desired UV, mass spectral and [.ID data were identical with those of olefinic compound 30 in 74% yield from diol 28. Finally the natural (19Z)-anhydrovobasinediol. protecting group on Nb was removed with Zn in acetic acid to We next turned our attention to the conversion of koumidine furnish N-demethoxyrankinidine 1 (m.p. 268-270 "C(decornp.), 3 into the oxindole alkaloid 1. We had found an efficient method [u]h4 -166" (c 0.45 in MeOH)} in 78% yield. The synthetic for the stereoselective oxidation-rearrangement of sarpagine-compound 1 had spectral properties ('H NMR, I3C NMR, IR, J.CHEM. SOC. PERKIN TRANS. I 1991 19 26 R=H 27 R=OMe iii I, OH I OH AH 28 29 iv -vi1 30 1 Scheme 3 Reagents: i, ClCO,CH,CCl,, MgO, aq. THF; ii, LiAlH,, THF; iii, OsO,, THF-Py; iv, pyridinium toluene-p-sulphonate, trimethyl orthoformate, THF; v, Ac,O; vi, 1 mol dm-, NaOH-MeOH; vii. Zn, AcOH UV, high-resolution mass, and CD) in accord with those of the natural product. In conclusion, we have undertaken a biogenetically patterned synthesis of three minor Gelsemiurn alkaloids, koumidine, (19Z)-anhydrovobasinediol [( 19Z)-tab-erpsychine], and N-demethoxyrankinidine, starting from ajmaline, in a stereoselective manner. Since the absolute configuration of ajmaline has already been established, the structure, including the absolute configuration, of the three products was determined.Experimental M.p.s were measured on a Yamato MP-21 apparatus and are uncorrected. IR spectra were measured with a Hitachi 260 spectrophotometer, and UV spectra were measured in ethanol with a Hitachi U3400 spectrophotometer. 'H NMR spectra were recorded on a JEOL JNM FX-270, a JNM GX-270 (270 MHz), or a JEOL GSX5OO (500 MHz) spectrometer with tetramethylsilane as internal standard. J-Values are given in Hz. 13CNMR spectra were measured with a JEOL GSX400 (100.4 MHz) or a JNM GX-270 (67.8 MHz) spectrometer with tetramethylsilane as internal standard. Mass spectra were taken with a Hitachi RMU-6E or an RMU-7M spectrometer. CD spectra were measured with a JASCO J-500A spectrometer for solutions in MeOH.Optical rotations were measured on a JASCO DIP- 140 polarimeter. Elemental analyses were measured with a Perkin-Elmer 240 elemental analyser. TLC was performed on Merk precoated silica gel 60F-254 plates. Column chromatography utilized Merk Silica gel 60 [7&230 and 230-400 mesh (for flash chromatography)], prepacked column [Kusano CPS-HS-221-05 (for medium-pressure column chromatography)], and Merk Al,03 (activity 11-111). Preparation of the Carbarnate 5 from Ajmaline 4.-A mixture of compound 4 (5.020 g, 15.3 mmol), N,N-dimethylhydrazine (4.70cm3, 61.9 mmol), a catalytic amount of H,SO,, molecular sieves 3 A, and ethanol (100 cm3) was heated under reflux for 5 h.The filtrate obtained upon filtration of the molecular sieves was concentrated under reduced pressure and then basified with aq. NH,OH. The aq. layer was extracted with chloroform and the extract was washed with water, dried (MgSOJ and evaporated. The residue was dissolved in 1 mol dm-3 NaOH- CH,Cl, (1:4; 250 cm3), and methyl chloroformate (1.42 cm3, 18.4 mmol) was added to the mixture at 0 "C. After 30 min additional methyl chloroformate (0.25 cm3, 3.2 mmol) was added to the reaction mixture, which was then stirred at 0 "C for 10 min. The organic layer was separated and the aq. layer was extracted with dichloromethane. The combined organic layers were washed with water, dried (MgSO,), and evaporated. The residue was purified by silica gel flash column chromatography with ethyl acetate-hexane (2: 1) to give the carbamate 5 (5.166 g, 79%) as an amorphous powder, &,,,(EtOH)/nm 290, 245 and 206; v,,,(CHCl,)/cm-' 3400, 1690 and 1460; 6,(270 MHz; CDCl,) 6.44 and 6.40* (1 H, each d, J 7.3, 21-H), 3.69 (3 H, s, C0,Me) and 2.75, 2.74 and 2.72 (each 3 H, s, 3 x NMe); rn/z 426 (M', 17%), 282 (61), 144 (98) and 113 (100).Hydrolysis of the Carbarnate 5.-Copper(11) chloride was * See footnote on p. 1773. added portionwise to a solution of the hydrazone 5 (6.186 g, 14.5 mmol) in a mixture of THF (218 cm'), water (29 cm3) and phosphate buffer (0.07 mol dm-,, pH 7; 87 cm3) at room temperature in the following manner: 0 min, 3.902 g (29.0 mmol); 18 h, 1.952 g (14.5 mmol); 25 h, 1.013 g (7.5 mmol).After the final additional of CuCl, the mixture was stirred at room temperature for 17 h. After concentration to remove ethanol the reaction mixture was diluted with ice-water and basified with aq. NH40H. The whole mixture was extracted with chloroform and the extract was washed with water, dried (MgSO,) and evaporated. The residue was purified by silica gel flash column chromatography with ethyl acetate-hexane (2 :3) to give the free aldehyde 6 (4.175 g, 75%) as an amorphous powder (Found: M ', 384.2050. C,,H,,N,O, requires M, 384.2048); A,,,(EtOH)/nm 290, 247 and 206; v,,,(CHC13)/cm-' 3450, 1720, 1690 and 1460; 6,(270 MHz; CDCl,) 9.62 (d, J 3.4) and 9.59 (d, J4.3) (together 1 H, 21-H), 3.73 and 3.72 (3 H, each s, CO,Me), 2.76 and 2.73 (3 H, each s, NMe) and 0.87 (3 H, td, J 7.4, 1.3, 18-H3); m/z 384 (M+, 65%), 240 (32), 198 (28), 173 (80), 168 (30) and 144 (100).Preparation of the Methoxyethoxymethyl Ether 7.-Methoxy-ethoxymethyl chloride (MEMCl) (45 mm3, 0.394 mmol) was added to a solution of the alcohol 6 (100 mg, 0.260 mmol) and diisopropylethylamine (68 mm3, 0.390 mmol) in dry dichloro- methane (2 cm3) at 0°C. The mixture was stirred at room temperature for 1.5 h and was then heated under reflux for 1.5 h. Additional diisopropylethylamine (90 mm3, 0.517 mmol) and MEMCl (45 mm3, 0.394 mmol) were added to the reaction mixture at 0 "C and the mixture was heated under reflux for 3 h. Cold 5% aq. sodium carbonate was added to the reaction mixture and the whole was extracted with chloroform.The extract was washed with water, dried (MgSO,), and evaporated. The residue was purified by MPLC with ethyl acetate-hexane (2:5) to afford the MEM ether 7 (100 mg, 81%) as an amorphous powder, A,,,(EtOH)/nm 292, 248 and 205; v,,,(CHC13)/cm-' 1720, 1690, 1460, 1120 and 1040; 6,(270 MHz; CDCl,) 9.60 (d, J 3.4) and 9.57 (d, J 4.6) (together 1 H, 21-H), 3.73 and 3.71 (3 H, each s, CO,Me), 3.384 and 3.382 (3 H, each s, OMe), 0.863 and 0.855 (3 H, each t, J 7.5,18-H3);m/z 472 (M+, 7579,252 (33), 182 (52), 144 (54), 89 (98) and 59 (100). Preparation of the Silyl En01 Ether 8.-TBSOTf (73 mm3, 0.318 mmol) was added to a solution of compound 7 (100 mg, 0.212 mmol) and triethylamine (44 mm3, 0.316 mmol) in dry dichloromethane (1 cm3) and the mixture was stirred for 1.5 h.Further triethylamine (73 mm3, 0.525 ,mmol) and TBSOTf (73 mm3, 0.318 mmol) were added to the reaction mixture at 0 "C and the mixture was then stirred at the same temperature for 1 h. Cold 5% aq. sodium carbonate was added to the mixture and the whole was extracted with dichloromethane. The extract was washed with water, dried (MgSO,), and evaporated. The residue was separated by MPLC with 10% ethyl acetate-hexane to give the silyl ether 8 (87 mg, 71%) as an amorphous powder (Found: M +,586.3419. C,,H,,N206Si requires M, 586.3435); I1,,,(EtOH)/nm 292,248 and 205; v,,,(CHCl,)/cm-' 1690,1460 and 840; 6,(270 MHz; CDCl,) 6.14 (1 H, br s, 21-H), 1.00 (3 H, t, J7.5, 18-H3), 0.128,0.118,0.111 and 0.107 (6 H, each s, SiMe,) and 0.92 (9 H, s, SiBu'); m/z 586 (M', 82%), 336 (97), 241 (33), 182 (67), 144 (61), 89 (100) and 59 (98).Bromination of the Silyl En01 Ether 8.-A solution of NBS (27 mg, 0.152 mmol) in dry THF (2 cm3) was added dropwise to a solution of compound 8 (80 mg, 0.136 mmol) in dry THF (2 cm3) at -18 "C and the mixture was stirred at the same temperature for 30 min. Saturated aq. ammonium chloride was added and the whole was extracted with chloroform. The extract was washed with water, dried (MgS0,) and evaporated. J. CHEM. SOC. PERKIN TRANS. 1 1991 The residue was purified by MPLC with ethyl acetate-hexane (1:4) to yield compound 9 (57 mg, 76%) as an amorphous powder, A,,,(EtOH)/nm 291, 244 and 205; v,,,(CHCl,)/ cm-' 1710, 1690, 1470 and 1110; 6,(270 MHz; CDCl,) 9.39 and 9.35 (1 H, each s, 21-H), 3.72 and 3.70 (3 H, each s, C0,Me) and 1.09 (3 H, t, J6.7,18-H3); m/z 552 (M+ + 2, lo%), 550 (M', 12), 182 (31), 144 (46), 89 (98) and 59 (100).Preparation of or$-Unsaturated Aldehydes from Bromide 9.-DBU (20 mm3, 0.134 mmol) was added to a solution of the bromide 9 (57 mg, 0.103 mmol) in dry DMF (1 cm3) and the mixture was stirred at room temperature for 16 h. Saturated aq. ammonium chloride was added and the whole was extracted with chloroform. The extract was washed with water, dried (MgS04) and evaporated. DMF was removed by Kugelrohr apparatus and the residue was purified by MPLC with ethyl acetate-hexane (2: 3) to afford 2-olefin 10 (29 mg, 60%) and E-olefin ll (6 mg, 12%).Compound 10 was an amorphous powder (Found: M +,470.2396. C26H34N206 requires M, 470.2414); A,,,(EtOH)/nm 292, 25 lsh, 230 and 206; v~,,(CHCl,)/cm-' 1690, 1670, 1460 and 1110; 6,(500 MHz; CDCl,) 10.20 and 10.19 (1 H,each s, 21-H), 6.67 (1 H, q-like, J7.7, 19-H) and 2.15 and 2.13 (3 H, each d, J 7.7, 18-H3); m/z 470 (M', loo%), 381 (26), 250 (74), 182 (91), 144 (90), 89 (90) and 59 (73). Compound 11 was an amorphous powder (Found: M+, 470.2409); A,,,(EtOH)/nm 293, 252, 224 and 207; v,,,-(CHCl,)/cm-' 1690, 1455 and 1110; 6,(500 MHz; CDCl,) 9.34 and 9.32 (1 H, each s, 21-H), 6.56 (1 H, q-like, J7.4, 19-H) and 2.07 and 2.03 (3 H, each d, J7.4 18-H,); m/z 470 (M', 79%), 381 (19), 250 (50),182 (61), 144 (63), 89 (66) and 59 (100).NaBH, Reduction of Z-Olejin 10.-Sodium borohydride (2.1 mg, 0.056 mmol) was added to a solution of enal 10 (25 mg, 0.053 mmol) in methanol (0.5 cm3) and the mixture was stirred at room temperature for 30 min. Water was added, and the whole was extracted with chloroform. The extract was washed with water, dried (MgSO,) and evaporated. The residue was separated by MPLC with ethyl acetate-hexane (2: 1) to afford the moll2 (22 mg, 88%) as an amorphous powder (Found: M+, 472.2572. C26H36N206 requires M, 472.2573); A,,,(EtOH)/ nm 291, 248 and 202; v,,,(CHCl,)/cm-' 3450, 1690, 1455 and 1110; 6,(270 MHz; CDCl,) 4.23 (2 H, br s, 21-H,), 5.49 and 5.44 (1 H, q, J 7.0, 19-H), 3.70 and 3.64 (3 H, each s, C0,Me) and 1.70 and 1.69 (3 H, each d, J7.0,18-H3); m/z 472 (M', 6873, 366 (14), 252 (22), 182 (59, 144 (68), 89 (53) and 59 (100).NaBH, Reduction of E-Olejn 11.-Identical treatment of enal 11 (370 mg, 0.786 mmol) in methanol (7.4 cm3) with sodium borohydride (30 mg, 0.793 mmol) afforded the enol 13 (243 mg, 65%) as an amorphous powder (Found: M+, 472.2585); I1,,,(EtOH)/nm 291, 248 and 202; v,,,(CHCl,)/ cm-' 3450, 1690, 1460 and 1120; 6,(270 MHz; CDCl,) 4.06 (2 H, br s, 21-H,), 5.60 (1 H, m, 19-H), 3.73 and 3.72 (3 H, each s, C0,Me) and 1.70 (3 H, d, J6.7,18-H3); m/z 472 (M +,60%), 366 (18), 252 (13), 182 (59), 144 (70), 138 (26), 89 (58) and 59 (100). Hydrolysis of the Alcohol 12.-A mixture of the enol carbamate 12 (100 mg, 0.212 mmol), sodium hydroxide (240 mg), ethylene glycol (4 cm3) and water (0.8 cm3) was heated under reflux for 6 h. Water was added to the reaction mixture and the whole was extracted with chloroform. The extract was washed with water, dried (MgSO,) and evaporated.The residue was passed through a short column of silica gel to give the free amine 14 (77 mg, 87%) as an amorphous powder, ~,,,(CHCl,)/crn-' 3300, 1480, 1100 and 1040. Hydrolysis of the Alcohol 13.-Identical treatment of the enal carbamate 13(190 mg, 0.402 mmol) with sodium hydroxide (480 J. CHEM. SOC. PERKIN TRANS. 1 1991 mg), ethylene glycol (8 cm3) and water (1.6 cm3) (reaction time 1 h) afforded the free amine 15 (141 mg, 85%) as an amorphous powder, v,,,(CHCl,)/cm~' 3400, 1480, 1090 and 1040.Preparation of Compound 16.-Mesyl chloride (0.30 cm3, 3.876 mmol) was added to a solution of the amine 14 (1556 mg, 3.754 mmol) in dry pyridine (60 cm3) at 0 "C and the mixture was stirred at room temperature for 30 min. After the addition of ice-water the reactionmixture was basified with aq. NH40H. The aq. layer was extracted with chloroform. The extract was washed with water, dried (MgSO,), and evaporated. The residue was separated by silica gel flash column chromatography with 2% methanol-chloroform to afford compound 16 (925 mg, 62%) as an amorphous powder (Found: M', 396.2399. C24H32N203 requires M, 396.2411); A,,,(EtOH)/nm 292, 249 and 205; v,,,(CHC13)/cm-' 1100, 1040 and 1020; 6,(270 MHz; CDCl,) 5.30 (1 H, qt, J6.7 and 2.3, 19-H), 3.6 (1 H, 21-H), 3.29 (1 H, br d, J 16.5,21-H) and 1.56 (3 H, d, J6.7, 18-H3); m/z 396 (M', loo%), 307 (33), 291 (35), 183 (37), 144 (24) and 59 (66).Preparation of 17.-Identical treatment of a solution of compound 15(140 mg, 0.338 mmol) in dry pyridine (3 cm3) with mesyl chloride (29 mm3, 0.375 mmol) afforded compound 17 (98 mg, 73%) as an amorphous powder (Found: M+, 396.2410); A,,,(EtOH)/nm 291, 248 and 205; v,,,(CHCl,)/cm-' 11 10, 1040 and 1020; 6,(270 MHz; CDCl,) 5.26 (1 H, q-like, J 6.7, 19-H), 3.55 (1 H, d, J 12.2,21-H), 3.4 (1 H, 21-H) and 1.65 (3 H, dt, J6.7 and 1.6, 18-H3); m/z 396 (M+, loo%), 307 (32), 291(31), 183 (36), 144 (20) and 59 (45). Hydrolysis of Compound l6.-Conc. HCl(1 drop) was added to a solution of compound 16 (50 mg, 0.126 mmol) in methanol (1 cm3) at 0 "C and the mixture was refluxed for 5 h.The reaction mixture was diluted with chloroform and then basified with cold 5% aq. sodium carbonate. The whole was extracted with 5% methanol-chloroform. The extract was washed with water, dried (MgSO,) and evaporated. The residue was crystallized from acetone to afford the alcohol 18 (37 mg, 95%) as needles, m.p. 279-281 "C (Found: C, 76.9; H, 7.75; N, 8.9. C20H,,N,0-~H,0 requires C, 76.76; H, 7.89; N, 8.95%); A,,,(EtOH)/nm 292, 248 and 205; v,,,(KBr)/cm-' 3050, 1605 and 740; 6,(270 MHz; CDCl,) 5.31 (1 H, qt, J 6.7 and 2.2, 19-H), 4.44 (1 H, S, 17-H), 3.62 (1 H, d, J 16.8, 21-H), 3.29 (1 H, br d, J 16.8, 21-H), 3.46 (1 H, d, J9.8, 3-H), 2.78 (3 H, s, N"Me), 2.64 (1 H, s, 2-H) and 1.57 (3 H, d, J6.7, 18-H,); 11% NOE was observed between 15-H, (6 2.65) and 19-H (6 5.31); m/z 308 (M', loo%), 291 (6), 277 (9), 183 (40), 182 (17), 157 (13), 144 (16) and 131 (6).Preparation of Tetraphyllicine 19.-Identical treatment of compound 17 (47 mg, 0.119 mmol) in methanol (1.5 cm3) with catalytic conc. HCl afforded tetraphyllicine 19 (28 mg, 77%) as needles, m.p. 294-296 "C (lit.,9 274-275 "C); + 16" (c 0.4 in pyridine) (natural [orlh' +19" (in pyridine)} (Found C, 76.85; H, 7.8; N, 8.95. Calc. for C2,H,,N20~~H,0: C, 76.98; H, 7.88; N, 8.98%); A,,,(EtOH)/nm 291, 249 and 205; v,,,-(KBr)/cm-' 3050, 1605, 765 and 740 6,[270 MHz; CDCl, + CD,OD (1: l)] 5.29 (1 H, q-like, J6.7, 19-H), 4.38 (1 H, d, J0.9, 17-H), 3.48 (1 H, d, J9.2,21-H), 2.76 (3 H, s, NaMe), 2.64 (1 H, s, 2-H) and 1.68 (3 H, dq, J 6.7 and 1.1, 18-H3); 7% NOE was observed between 18-H3 (6 1.68) and 21-H (6 3.3); m/z 308 (M+, loo%), 291 (5), 277 (8), 183 (43, 182 (22), 168 (12), 157 (16), 144 (25) and 131 (11).It was identical with an authentic sample (TLC, mixed m.p.). Preparation of the TBS Ether 20.-TBSOTf (90 mm3, 0.392 mmol) was added to a stirred mixture of the alcohol 18(100 mg, 0.324 mmol) and triethylamine (68 mm3, 0.489 mmol) in dry dichloromethane (10 cm3) at 0 "C and the mixture was stirred at the same temperature for 1 h. After the addition of further TBSOTf (45 mm3, 0.196 mmol) at 0°C the reaction mixture was stirred at 0°C for 1 h. Cold 5% aq. sodium carbonate was added to the mixture and the whole was extracted with chloroform.The extract was washed with water, dried (MgSO,) and evaporated. The residue was purified by silica gel column chromatography with 2% methanol-chloroform to give compound 20 (1 10 mg, 80%) as an amorphous powder, A,,,(EtOH)/nm 291, 249 and 205; 6,(270 MHz; CDCl,) 5.32 (1 H, qt, J6.7 and 2.3, 19-H), 4.33 (1 H, s, 17-H), 1.57 (3 H, dd, J6.7 and 0.6 18-H3), 0.97 (9 H, s, SiBu') and 0.15 and 0.14 (each 3 H, s, SiMe,); m/z 422 (M', loo%), 278 (31), 277 (31), 182 (36) and 73 (21). Preparation of the Indolenine 22from the Indoline 20.-Lead tetraacetate was added portionwise to a stirred solution of compound 20 (39 mg, 0.092 mmol) in dry dichloromethane (1 cm3) at -70 "C in the following manner: 0 min, 48 mg (0.097 mmol); 20 min, 48 mg; 40 min, 48 mg; 80 min, 48 mg.The reaction mixture was stirred at -70 "C for 40 min, the temperature was gradually raised to 0 "C during 30 min, and the mixture was stirred at 0°C for 3 h. Cold aq. 5% sodium carbonate was added to the reaction mixture and the whole was extracted with 5% methanol-chloroform. The organic layer was washed with water, dried (MgSO,), and evaporated. The residue was purified by silica gel flash column chromatography with 2% methanol-chloroform to give compound 22 (22 mg, 59%) was an amorphous powder, A,,,(EtOH)/nm 253, 225sh, 221 and 214sh; v,,,(CHC13)/cm-' 1590 and 830; 6,(270 MHz; CDCl,) 5.37 (1 H, qt, J6.7 and 2.2, 19-H), 4.16 (1 H, dd, J7.6 and 2.5,3-H), 1.60 (3 H, d, J6.7, 18-H3), 0.94 (9 H, s, SiBu') and -0.01 and -0.09 (each 3 H, s, SiMe,); m/z 406 (M', loo%), 349 (22), 248 (39), 247 (34), 181 (21), 168 (39) and 73 (40).Preparation of 16-epi-Koumidine 25.-A solution of Bu,NF in THF (148 mm3, 0.148 mmol) was added to a solution of 25 (30 mg, 0.074 mmol) in THF (0.6 cm3). The mixture was stirred at 0 "C for 15 min and then at room temperature for 15 min. Water was added to the reaction mixture and the whole was extracted with 5% methanol-chloroform. The extract was washed with water, dried (MgSO,) and evaporated. The resulting aldehyde was subjected to the next reaction without chromatographic purification. Sodium borohydride (5.6 mg, 0.148 mmol) was added to a solution of aldehyde in methanol (0.5 cm3) at 0°C and the reaction mixture was stirred at room temperature for 30 min.Cold 5% aq. sodium carbonate was added to the reaction mixture and the whole was extracted with 5% methanol-chloroform. The extract was washed with water, dried (MgS0,) and evaporated. The residue was purified by silica gel column chromatography with 5-10% methanol-chloroform to give 16- epi-koumidine 25 (13 mg, 60%) as needles, m.p. 169-173 "C (Found: C, 76.3; H, 7.6; N, 9.3. C,,H,,N,O*~H,O requires C, 76.35; H, 7.59; N, 9.37%); A,,,(EtOH)/nm 289sh, 279 and 226; v,,,(KBr)/cm-' 3230, 1450, 1030 and 740; 6,(270 MHz; CD,OD) 5.34 (1 H, qt, J 7.0 and 2.4, 19-H), 4.17 (1 H, dd, J 10.1 and 2.1, 3-H), 3.46 (2 H, d, J 7.3, 17-H~) and 1.60 (3 H, d, J 7.0, 18-H3); 6,(67.8 MHz; CD,OD) 138.2 (s, C-2), 51.6 (d, C-3), 56.8 (d, C-5), 27.9 (t, C-6), 104.0 (s, C-7), 128.8 (s, C-8), 119.9 (d, C-9), 118.6 (d, C-lo), 122.1 (d, C-ll), 112.0 (d, C-12), 136.3 (s, C-13), 35.9 (t, C-14), 35.7 (d, C-15), 45.3 (d, C-16), 65.3 (t, C-17), 12.6 (9, C-18), 118.7 (d, C-19), 139.0 (s, C-20) and 54.1 (t, C-21); m/z 294 (M', loo%), 293 (95), 277 (ll), 263 (36), 182 (ll), 169 (82) and 168 (53).Preparation of the Indolenine 23 from the Indoline Alcohol 18.-TMSOTf (188 mm3, 0.973 mmol) was added to a stirred mixture of compound 18 (200 mg, 0.649 mmol) and tri-ethylamine (0.14 cm3, 1.006 mmol) in dry dichloromethane (4 cm3) at 0 "C and the mixture was stirred at room temperature for 30 min.The reaction mixture was diluted with chloroform and the organic layer was washed with water, dried (MgSO,) and evaporated. The resulting trimethylsilyl ether was subjected to the next reaction without chromatographic purification. To a stirred solution of the trimethylsilyl ether in dry dichloromethane (4 cm3) was added Pb(OAc), in the following manner. Initially, Pb(OAc), (320 mg, 0.650 mmol) was added to the mixture at -68 "C and the mixture was stirred at the same temperature for 20 min. After the addition of one more mole equivalent of Pb(OAc), at -68 "C, the temperature was gradually raised to -15 "C during 30 rnin and the mixture was stirred at from -15 "C to -8 "C for 3 h. Pb(OAc), (320 mg) was added to the mixture cooled to -68 "C and the tem- perature was raised to -15 "C during 20 min.After 3 h, further Pb(OAc), (160 mg, 0.325 mmol) was added at -68 "C. The temperature was raised to -15 "C during 20 rnin and the mixture was stirred at from -15 "C to -10 "C for 1 h. Further Pb(OAc), (160 mg) was added at -68 "C and the temperature was raised to -15 "C during 15 min. The mixture was stirred at -15 "C for 40 min and then was diluted with chloroform and washed with cold 5% aq. sodium hydrogen carbonate. The aq. layer was extracted with chloroform. The combined organic layers were washed with water, dried (MgSO,), and evaporated. The residue was purified by silica gel flash column chromato- graphy with 3% methanokhloroform to give compound 23 (149 mg, 63%) as an amorphous powder, A,,,(EtOH)/nm 261, 226sh, 221 and 215sh.Preparation of Koumidine 3 from the Indolenine 23.-To a solution of 23 (202 mg, 0.554 mmol) in THF (1.2 cm3) at 0 "C were added water (1.2 cm3) and acetic acid (3.6 cm3) and the mixture was stirred at the same temperature for 1 h. Sodium cyanoborohydride (105 mg, 1.671 mmol) was added to the reaction mixture still cooled to 0 "C and the mixture was then stirred at room temperature for 50 min. The mixture was diluted with 5% methanol-chloroform and basified with cold aq. NH,OH. The aq. layer was extracted with 5% methanol-chloroform. The extract was washed with water, dried (MgSO,), and evaporated. The residue was purified by silica gel column chromatography with 1-5% methanol-chloroform to afford koumidine 3 (126 mg, 77%) as needles, m.p.202-204 "C (natural koumidine has m.p. 20G201 "C; [a];, -23.8" (c 0.6 in MeOH) {natural [a]$' -20.8' (c 1.8 in MeOH)} (Found: M+, 294.1733. Calc. for C,,H,,N,O: M, 294.1731); A,,,(EtOH)/nm 289sh, 282 and 227; v,,,(KBr)/cm-' 3200, 1450, 1035, 1220 and 740; 6,(270 MHz; CD,OD) 5.37 (1 H, qt, J6.7,2.6, 19-H), 4.12 (1 H, dd, J9.8 and 3.7, 3-H), 3.76 (1 H, J. CHEM. SOC. PERKIN TRANS. I 1991 by silica gel flash column chromatography with 30% ethyl acetate-hexane to give compound 26 (48 mg, 58%) as an amorphous powder, &,,,(EtOH)/nm 293sh, 284 and 223; 6,(500 MHz; CDCI,) 7.95 and 7.90 (1 H, each s, N"H), 5.47 and 5.38 (1 H,q-like,J6.9, 19-H),5.18(1H,d,J9.1,3-H)and1.63and1.53 (3 H, d, J 6.9, 18-H3); m/z 470 (M+ + 2, 36%), 468 (M+, 37), 434 (18), 368 (12), 44 (40) and 36 (100).Preparation of (19Z)-Anhydrovobasinediol 2 from the Carbamate 26.-Lithium aluminium hydride (42 mg, 1.105 mmol) was added to a solution of compound 26 (48 mg, 0.102 mmol) in dry THF (2 cm3) at 0 "C and the mixture was stirred at room temperature for 1.5 h. After decomposition of excess of lithium aluminium hydride with aq. THF, the reaction mixture was filtered. The filtrate was concentrated, and purified by silica gel flash column chromatography with 3% methanol-chloro- form to give compound 2 (27 mg, 86%) as an amorphous powder, [a]h3 -151" (c 0.3 in CHC1,) {natural (192)- anhydrovobasinediol has -180" (c 0.4 in CHCl,)); A,,,(EtOH)/nm 292, 285, 280sh and 224; v,,,(CHCl,)/cm-' 3460, 1460, 1340 and 1075; 6,(500 MHz; CDC1,) 7.92 (1 H, s, N"H), 5.43 (1 H, q-like, J6.9, 19-H), 5.12 (1 H, d, J9.9,3-H), 2.60 (3 H, s, NbMe) and 1.60 (3 H, d, J 6.9, 18-H3); m/z 308 (M+, loo%), 293 (25), 279 (12), 154 (15) and 122 (90). It was identical with an authentic sample on comparison of 'H NMR and chromatographic behaviour.Osmylation of the Carbamate 26. A solution of osmium tetraoxide (51 mg, 0.021 mmol) in dry THF (1 cm3) was added dropwise to a solution of compound 26 (45 mg, 0.096 mmol) in a mixture of dry THF (1 cm3) and dry pyridine (1 cm3) at -20 "C. The mixture was then stirred at the same temperature for 40 min. Aq. sodium hydrogen sulphite [lo0 mg in water (2 cm3)] was added and the mixture was stirred at room temperature for 1.5 h.Water was added to the reaction mixture and the whole was extracted with chloroform. The extract was washed with brine, dried (MgSO,) and evaporated. The residue was purified by MPLC with 2% methanol-chloroform to afford the oxindole 28 (19 mg, 38%) and the indole 29 (1 8 mg, 37%). Compound 28: amorphous powder (Found: M', 518.0764. C22H25C13N206 requires M, 518.0775); A,,,(EtOH)/nm 279sh, 251 and 208; 6,(500 MHz; CDCl,) 1.30 and 1.27 (3 H, each d, J 6.3, together 18-H,); mjz 520 (M + 2,12735 18 (1 2), + 372 (12), 146 (82) and 36 (100); CD Acjnrn (c 0.21 mmol dm-,, MeOH; 25 "C) -36.2 (209), + 11.3 (227), -6.6 (254) and -1.9 (280). Compound 29: amorphous powder, A,,,(EtOH)/nm 293sh, 284 and 223; 6,(500 MHz; CDCl,) 8.12 and 8.10 (1 H, each s, N"H), 5.21 and 5.20 (1 H, each d, J 10.2, 3-H) and 1.30 and 1.27 (3 H, each d, J 6.3, 18-H3).brd,J17.1,21-H),3.52(1H,dd,J10.7and6.4,17-H),3.15(lH, Preparation of the Oxindole 28 j?om the Indole dd, J 10.8 and 9.0, 17-H) and 1.61 (3 H, dt, J6.7 and 1.5, 18-H,); m/z 294 (M+, loo%), 293 (91), 277 (14), 263 (44), 249 (ll), 182 (ll), 169 (99), 168 (67), 156 (10) and 115 (10). It was identical with an authentic sample on comparison of chromatographic behaviour (TLC), mixed m.p. and 'H NMR data. Preparation of the Carbanate 26 from Koumidine 3.-2,2,2-Trichloroethyl chloroformate (0.36 cm3, 2.615 mmol) was added to a stirred mixture of koumidine 3 (52 mg, 0.177 mmol) and magnesium oxide (145 mg, 3.596 mmol) in THF (4 cm3k water (1 cm3) at 0 "C and the mixture was then stirred at room temperature for 30 min.After the addition of further ClCO,CH,CCl, (0.05 cm3, 0.363 mmol) to the mixture at 0 "C the reaction mixture was stirred at room temperature for 30 min. Cold water (5 cm3) was added to the mixture and the whole was extracted with chloroform. The extract was washed with brine, dried (MgS0,) and evaporated. The residue was purified 29.-A solution of OsO, (16.1 mg, 0.063 mmol) in dry THF (0.6 cm3) was added dropwise to a stirred mixture of the indole 29 (28 mg, 0.056 mmol), dry THF (0.6 cm3) and dry pyridine (0.6 cm3) at -28 "C and the mixture was stirred at from -28 "C to -15 "C for 1.5 h. Aq. sodium hydrogen sulphite [60 mg in water (0.6 cm3)] was added to the mixture at 0 "C and the mixture was then stirred at room temperature for 2 h.Water was added to the reaction mixture and the whole was extracted with chloroform. The extract was washed with brine, dried (MgSO,) and evaporated. The residue was separated by MPLC with 2% methanokhloroform to give the oxindole 28 (16 mg, 55%) and the starting material 29 (6 mg, 2104 recovery). Prepuration of the Ole$nic- Compound 30 ,from the Oxindole 28.-Pyridinium toluene-p-sulphonate ( 11 mg, 0.044 mmol) and trimethyl orthoformate (48 mm3, 0.439 mmol) were added to a solution of compound 28 (45 mg, 0.087 mmol) in dry THF J. CHEM. SOC. PERKIN TRANS. 1 1991 (1 an3).The mixture was stirred at room temperature for 3 h.The solution was passed through a short column of silica gel and was then concentrated. The resulting 1,3-dioxolane was dissolved in acetic anhydride (1 cm3) and the solution was refluxed for 2 h. The reaction mixture was diluted with ice-water and basified with cold aq. NH40H. The whole was extracted with chloroform and the extract was washed with water, dried (MgSO,) and evaporated. The residue was dissolved in 1 mol dm-, NaOH-methanol (1 cm3) and the mixture was stirred at room temperature for 1 h. Water was added to the reaction mixture and the whole was extracted with chloroform. The extract was washed with brine, dried (MgSO,), and evaporated. The residue was purified by MPLC with ethyl acetate-hexane (1 :2) to afford compound 30 (31 mg, 74%) as an amorphous powder (Found: M', 484.0731.C2,H,,C13N,04 requires M, 484.0722); &,,,(EtOH)/nm 279, 250 and 206; v,,,(CHCl,)/ cm-' 3440, 1710, 1420 and 1120; 6,(270 MHz; CDCl,) 8.24 and 8.19 (1 H, each s, NaH), 5.67 (1 H, m, 19-H) and 1.74 (3 H, d, J 5.9, 18-H,); m/~486 (M' + 2, 26%), 484 (M', 29), 339 (20), 310 (25), 208 (23), 146 (100) and 133 (24). Preparation of N-Demethoxyrankinidine 1.-Zinc dust was added to a solution of compound 24 (28 mg, 0.058 mmol) in acetic acid (1 cm3) at room temperature in the following manner: 0 min, 40 mg (0.612 mmol); 2 h, 15 mg (0.229 mmol); 4 h, 30 mg (0.459 mmol). The mixture was stirred for 2 h and was then filtered, and diluted with ice-water. The mixture was basified with cold aq. NH40H and the whole was extracted with 10% methanokhloroform.The extract was washed with brine, dried (MgS04), and evaporated. The residue was crystallized from acetone to afford compound 1 (14 mg, 78%) as prism, m.p. 268-270 'C (lit.,2e 258-260 "C); [a]h4 -166" (c 0.45 in MeOH) (lit.,2" -169.2' (c 0.052 in MeOH)} (Found: M+, 310.1671. Calc. for C,,H,,N,O,: M, 310.1679); L,,,(EtOH)/nm 278sh, 252 and 207; v,,,(KBr)/cm-' 3280 and 1700; 6"(500 MHz; CDCl,) 5.23 (1 H, q-like, J 6.6, 19-H), 4.33 (1 H, d, J 10.5, 17-Ha), 4.05 (1 H, dd, J 10.5 and 4.7, 17-H8), 3.88 (1 H, d, J 16.8, 21-HB), 3.59 (1 H, d, J8.5,3-H), 3.32 (1 H, d, J 16.8, 21-H") and 1.60 (3 H, d, J 6.6, lS-H,); 6,(100.4 MHz; CDCl,) 181.1 (s, C-2), 73.9 (d, C-3), 54.3 (d, C-5), 33-7 (t, C-6), 58.7 (s, C-7), 135.3 (s, C-S), 125.1 (d, C-9), 122.9 (d, C-lo), 128.1 (d, C-ll), 109.7 (d, C-12), 139.3 (s, C-13), 29.7 (t, C-14), 33.9 (d, C-15 and -16), 66.9 (t, C-17), 12.7 (4, C-lS), 118.8 (d, C-19), 138.7 (s, C-20) and 41.1 (t, C-21); m/z 310 (M+, 96%), 295 (38), 164 (51) and 108 (100); CD A&/nm (c 0.35 mmol dm-3, MeOH; 24 "C) -21.2 (210), + 17.4 (229), -7.7 (256) and -2.4 (282).It was identical with an authentic sample on comparison of mixed m.p. and spectroscopic data. Acknowledgements This work was supported by a Grant-in-Aid (No. 01470136) from the Ministry of Education, Science and Culture, Japan, which is gratefully acknowledged. We thank Professor P. J. Scheuer, University of Hawaii, and Professor G.A. Cordell, University of Illinois, for providing a sample of natural tetraphyllicine and one of N-demethoxyrankinidine, respec- tively. Thanks are also due to Mrs. H. Seki, Miss R. Hara, Mr. T. Kuramochi and Mrs. Y. Imamoto in the Analytical Center of Chiba University for measurement of spectral data and elemental analysis. References 1 Z.-J. Liu and R.-R.Lu, The Alkaloids, ed. A. Brossi, Academic, New York, 1988, vol. 33, ch. 2. 2 (a) Y. Shun, G. A. Cordell and M. Garland, J. Nar. Prod., 1986, 49, 806; (b) S. Sakai, S. Wongseripipatana, D. Ponglux, M. Yokota, K. Ogata, H. Takayama and N. Aimi, Chem. Pharm. Bull., 1987, 35, 4668; (c) D. Ponglux, S. Wongseripipatana, H. Takayama, K. Ogata, N. Aimi and S. 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Ang, C. Egli, N. Nakatsuka, S. K. Sarkar and Y. Yasunari, J. Am. Chem. Soc., 1967,89,2506; L. K. Oliver and E. E. van Tamelen, f.Am. Chem. SOC., 1970, 92, 2136; M. F. Barlett, R. Sklar, W. I. Taylor, E. Schlitter, R.L. S. Amai, P. Beak, N. V. Bringi and E. Wenkert, f.Am. Chem. SOC., 1962,84,622. 7 H. Takayama, M. Horigome, N. Aimi and S. Sakai, Tetrahedron Lett., 1990,31, 1287. 8 E. J. Corey and S. Knapp, Tetrahedron Lett., 1976,3667. 9 P. J. Scheuer, M. Y. Chang and H. Fukami, J. Org. Chem., 1963,28, 2641. 10 M. F. Bartlett, B. F. Lambert and W. I. Taylor, J. Am. Chem. SOC., 1964,86,729. 11 H. Takayama, K. Masubuchi, M. Kitajima, N. Aimi and S. Sakai, Tetrahedron, 1989,45, 1327. 12 H. Takayama, H. Odaka, N. Aimi and S. Sakai, Tetrahedron Lett., 1990,31,5483. 13 F. Finch and W. 1.Taylor, J.Am. Chem. Soc., 1962,84, 1318. 14 M. Ando, H. Ohhara and K. Takase, Chem. Lett., 1986,879. Paper 1/01178B Received 12th March 1991 Accepted 21st March 1991