摘要:

1977 2443Naturally Occurring Compounds Related to Phenalenone. Part 8. Struc-ture and Synthesis of DemethylherqueichrysinBy David A. Frost, David D. Halton, and George A. Morrison, * Department of Organic Chemistry, The Uni-The isolation of herqueichrysin from Penicilhum herqueiand its conversion into atrovenetin (1 b) are described. Thestructure of dernethylherqueichrysin (3a) (8,9-dihydro-2,3,4,7-tetrahydroxy-6,8,8,9-tetramethylphenaleno[1.2-blfuran-I -one) ts established by synthesisfrom 9-hydroxy-6.7.8-trimethoxy-4-methyl-3- (3-methylbut-2-enyloxy) -phenalen-I -one ( 6 ) . The isolation of partially racemised atrovenetin (1 b) and deoxyherqueinone ( l a ) from P.herquei is also described.versity, Leeds LS2 9JTAs reported in our preliminary communication,2a wehave isolated, during an investigation of the metabolicproducts of PeniciZZium herqztei grown in submerged cul-ture, a hitherto undescribed metabolite, isomeric withdeoxyherqueinone (la).The new metabolite exhibitedi.r., u.v., and n.m.r. spectra characteristic of a methoxy-trihydrox yp h enalenone fused to a 2,3,3- t rimet hyldi-hydrofuran ring, and gave a triacetate (with aceticanhydride-pyridine at room temperature), a dimethylether (upon treatment with ethereal diazomethane a t0 "C) and a trimethyl ether .(when treated at room tem-perature with ethereal diazomethane). Further, thematerial obtained by demethylation with pyridinehydrochloride or hydriodic acid was not identical withatrovenetin (lb) ; it followed that in the new metabolitePart 7, J .S. Brooks and G. A. Morrison, J.C.S. Perkin I,1974, 2114.Preliminary accounts, ( a ) D. A. Frost and G:A. Morrison,Tetrahedron Letters, 1972, 4729; (b) D. D. Halton and G. A. Morri-son, ibid., 1975, 1443.the orientation of the ether ring must differ from thatin the other phenalenone-derived pigments of P. herquei.After completion of our preliminary studies, Narasim-hachari and Vining reported the isolation of a new me-tabolite of herqueinone which they named herqueichrys-in.3 The identity of their material and ours was subse-quently established by direct comparison.If herqueichrysin, like atrovenetin (lb) and norher-queinone (13a) ,* is biosynthesised by oxidation andprenylation of an intermediate acetate-polymalonatederived chain [e.g.(2)], followed by closure to a cyclicether, three possible structures, (3a), (4), and ( 5 ) , may bewritten for its demethyl derivative. Other structureswhich would arise by oxidation or alkylation at C-12 ofthe polyketide chain (2) are excluded since the aromaticN. Narasimhachari and L. C. Vining, J . Antibiotics, 1972, $25,R. Thomas, Biochem. ,I., 1961, 78. 807; P w e AppZ. Chem.,155 (Chem. Abs., 1972, 76, 153,460).1973, 34, 5152444 J.C.S. Perkin Iproton and the aromatic methyl group of herqueichrysinare on adjacent positions in the aromatic nucleus, as in-dicated by coupling between them in the n.m.r. spec-t r ~ m . ~OR2R' 012( 3 ) a ; R = Hb; R = Me ( 4 1OH0 M eO0. C H 2.C H :CMe2( 5 ) (6)This paper describes a synthesis of compound (3a), nowshown to be identical with demethylherqueichrysin ;syntheses of compounds (4) and (5) will be the subject ofa later paper.Claisen rearrangement of the allyl ether (6) in dimethyl-formamide a t 100 "C to give (&)-atrovenetin yellow tri-methyl ether (lc) has previously been des~ribed.~ Inthe present work the allyl ether (6) was rearranged underthe same conditions, but in the presence of potassiumcarbonate to inhibit cyclic ether formation ; the product(yield 87%) was the 1,3-diketone (7a).The assignmentof structure (7a) rather than the tautomeric phenalenonestructure (8a) rests on the i.r. carbonyl absorption at1 674 cm-l and an n.m.r. singlet at T 6.53, attributable toH-2.The preferred adoption of the diketone tautomericform is possibly a consequence of the considerable stericcompression associated with the phenalenone structure(84.* This compound was origina.lly wrongly assigned structure(8b)*a (cf. ref. 2b).Treatment of the diketone (7a) with diazomethanegave two isomeric methyl ethers, which were separatedby chromatography. The structure of the major pro-duct (7b) * (68% yield) follows from its i.r. (vmax. 1650and 1 684 cm-l) and n.m.r. (singlet at T 6.55, H-2) spectra,and from the compounds obtained from it by prolongedtreatment with silver oxide and boiling methyl iodide ;these were the C-methylated derivative (7c), which ex-hibited spectra closely similar to those reported for theanalogous compound (7d),5 and the iodo-ethers (9) and(10).The structures assigned to the iodo-ethers, theproduction of which presumably arises from the presencein the methyl iodide of some elemental iodine, are fullysupported by the analytical, mass spectral, and n.m.r.data recorded in the Experimental section.M eO M& Me!&/ /R2 00 \ \( 7 ) ( 8 )a; R1 = R 2 = H a; ~1 = ~2 = Hb; R1 = Me, R2 = Hc; R ' = R 2 = Med; R1 = M e , R 2 = CMez*CH:CH2OMeMe0I( 1 1 1Treatment of the tetramethyl ether (7b) with toluene-$-sulphonic acid gave the dihydrofuran derivative (Id),a hitherto unknown tetramethyl ether of atrovenetin,which was smoothly demethylated with hydriodic acidto yield (A) -atrovenetin (lb). Since the tetramethylether (Id) is not identical with atrovenetin tetramethylether B [previously formulated as either (Id) or ( l l ) ] itD.A. Frost and G. A. Morrison, J.C.S. Perkin I, 1973, 2388.D. H. R. Barton, P. de Mayo, G. A. Morrison, and H.Raistrick, Tetrahedron, 1959, 6, 48; I. C. Paul, G. A. Sim, andG. A. Morrison, PYOC. Chem,. SOC., 1963, 352: 1 . C. Paul and G. A.Sirn, .I. Chrm. Soc., 1966, 10971977 2445follows that the latter is correctly represented by struc-ture (11).With the structure of the major product arising bytreatment of the diketone (7a) with diazomethane thusestablished as (7b), the minor product (which also con-tains four methoxy-groups) may be assigned structure(8b). This formulation is supported by an n.m.r. signalat very low field ( T - 8.7), characteristic of a 9-hydroxy-phenalenone. Upon treatment with toluene-9-sulphonicacid compound (8b) was converted into the tetracycliccompound (3b), demethylation of which with hydrogeniodide then gave (&)demethylherqueichrysin (3a), whichexhibited i.r., u.v., and n.m.r.spectra and t .l.c. behaviouridentical with those recorded for the same materialderived from a natural source.When demethylation of the ether (3b) was carried outby prolonged treatment with pyridine hydrochloride at220" there was obtained a mixture of (&)-demethylher-queichrysin (3a) and (&)-atrovenetin (lb), which wereseparated as their tetra-acetates. Similar treatment of(+)-demethylherqueichrysin, followed by acetylation,gave a mixture of (+)-demethylherqueichrysin tetra-acetate (33% yield; 83% optical purity) and (&)-atro-venetin tetra-acetate (30% yield).It thus appearsthat when demethylherqueichrysin is subjected to strin-gent acidic conditions, it is partly converted into atro-venetin by cleavage of its dihydrofuran ring and re-cyclisation (Scheme). The fact that the unrearrangedOHSCHEMEdemethylherqueichrysin which is recovered is of highoptical purity indicates that ring closure of the inter-mediate cation (12) occurs mainly to afford atrovenetin.During the present investigation, in addition to her-queichrysin, atrovenetin (lb) and deoxyherqueinone (la)were isolated from the mycelium of P. herquei grown insubmerged culture.' The possibility that under theseculture conditions P.herquei gives rise to both (+)-(I?)-and (-)-(S)-atrovenetin which serve as biosyntheticprecursors for herqueinone (13b) and its C-9 epimer,isoherqueinone, respectively (through the appropriateenantiomer of deoxyherqueinone 8), has already beenm ~ o t e d . ~ In accord with this view the atrovenetin isol-ated in the present work and its tri- and tetra-acetateshave specific rotations of +54.6",* +39.4", and +18.3",respectively. Since the corresponding [a], values for(+)-(R)-atrovenetin and its acetates derived from P.atroveneturn are +100.6",* +74.9", and +34", the atro-* Dioxan solution : all other specific rotations refer t o chloro-form solutions.venetin obtained from Y. herquei has an optical purityof only 54%. Similarly the deoxyherqueinone isolatedORin the present work gave a diacetate,[a]],, +43.6", whichcorresponds to an optical purity of 53%, assuming a valueof +8Z" for the specific rotation of the pure enanti~mer.~Atrovenetin is stable to the conditions employed in ex-tracting the mycelial products ; while the occurrence ofracemisation during the growth of P.herquei is not ex-cluded, the possibility remains that both (+)- and (-)-atrovenetin are metabolites of P. herquei.I t may be that demethylherqueichrysin is also a me-tabolite and that it undergoes isomerisation to (&)-atrovenetin (cf Scheme), thereby giving rise to the S-enantiomer of atrovenetin,EXPERIMENTALM.p.s were measured with a fiofler hot-stage apparatus.1.r. spectra were recorded with a Unicani SP 1000 G orPerkin-Elmer 125 instrument, for Nujol iiiulls unless statedotherwise.U.V. spectra were recorded with a Unicani SP800 spectrophotometer, using 95% ethanol as solvent.K.ii1.r. spectra were recorded with a Perkin-Elmer K12B or1232 spectrophotometer or a Varian A60A instrument,using deuteriochloroform as solvent, unless specified other-wise. Mass spectra were recorded with an A.E.I. MS 902spectrometer. Optical rotations were measured with aPerkin-Elmer 141 polarimeter using chloroform solutions ina 1 dni cell, unless otherwise stated. T.1.c. was carried outusing plates coated with Merck Kieselgel G or GF,,,. Lightpetroleum refers to the fraction of boiling range 60-80 "C.Solutions in organic solvents were dried with anhydroussodium sulphate or magnesium sulphate.Isolation of Herqueichrysin and Related Metabolites fromPenicillium herquei .---The culture of P.herquei used inthese studies was of strain number I.M.I. 89376. The growthconditions were the same as those already described.' Themycelium was separated from the culture fluid by filtration,pressed on a Buchner funnel under suction to remove asmuch moisture as possible, then continuously extractedwith ether (Soxhlet) for 48 h. Evaporation of the extractgave a yellow-brown powder (6.0 g from 2.8 1 of culture fluid).A portion (2.8 g) of this material was treated with aceticanhydride (10 ml) and pyridine (20 ml) for 4 days. Chroma-tography of the crude product on kieselgel G (300 g) usingether-benzene (3 : 7) as eluant afforded three major pro-ducts: deoxyherqueinone diacetate (158 mg), whichcrystallised from chloroform-light petroleum as yellow' N.Narasimhachari, K. S. Gopalkrishnan, R. H. Haskins, andL. C. Vining, Canad. J . Microbiol., 1963, 9, 134.A. B. Kriegler and R. Thomas, Chem. Comm., 1971, 738.J . S. Brooks and G. A. Morrison, J.C.S. Perkin I, 1972, 421J.C.S. Perkin Ineedles, m.p. 174-176", [a], +43.6" (c 0.7), atroveiietintriacetate (176 mg), which crystallised from methanol asyellow needles, m.p. 185-187", [a], +39.4" ( c 0.8), andherqueichrysin triacetate (570 mg) , which crystallised frombenzene-light petroleum as yellow rosettes, m.p. 187-188"(lit.,, ISSO), [a], +129.l" (c 1.3) (Found: C, 65.0; H, 5.45.Calc. for C2,H2,0,: C, 64.7; H, 5.45%), hl,,.,x.219, 243,264infl, 353 nm (log E 4.49, 4.58, 4.28, and 4.23) ; v,,,,,. 1 622,1641, 1771, and 1788 cn1-l; 'c 2.84 ( 1 H, s, ArH), 5.47( 1 H, q, J 7 Hz, OCHMe), 6.10 (3 H, s, ArOMe), 7.04 (3 H, s,ArMe), 7.60 (9 H, s, OAc), 8.50 and 8.73 (each 3 H, s, CMe,),and 8.58 (3 H, d, J 7 Hz, OCHMe).A second portion (1.8 g) of the material obtained byextraction of the mycelium with ether was washed withacetone, and recrystallised from acetone to yield atrove-netin (290 mg), [aID +55" (c 0.92, in dioxan), which gavei.r. and U.V. spectra identical with those of an authenticspecimen extracted from P. atrovenetum. Acetylation of asample (220 mg) of this material with acetic anhydride(0.7 ml) and pyridine (1.4 ml) for 16 11 gave a mixture ofatrovenetin triacetate (161 mg), m.p.186---187" (fromMeOH), [a], +39" (c 0.5) and atrovenetin tetra-acetate(98 mg), m.p. 183-185" (from benzene-light petroleum),[a], +IS" (c 0.7), which were separated by preparativet.1.c. The material obtained by evaporation of the acetonewashings was chromatographed on kieselgel G (150 g) usingether-benzene ( 1 : 9) as eluant. From the orange band ofhigher Rp value was obtained a mixture of herqueinone andisoherqueinone (484 mg) (75 : 25, according to the n.m.r.spectrum), identified by comparison of t.1.c. and spectraldata with those of an authentic mixture. The yellow bandof lower R%q value yielded herqueichrysin (520 mg). Thismaterial, which was also obtained by saponification of itstriacetate (see above), crystallised from chloroform-lightpetroleum as fine yellow needles, m.p.166-167" (lit.,,174"), [a],, +144" (c 0.5) (Found: m/e, 356.1271. Calc.for C,,H,,O,: M , 356.1260), hhllliLX. (CH,Cl,) 248, 283, and376 nm (log E 4.28, 3.94, and 4.17); vllWx. (CHCI,) 1 600,1 640, 3 430, and 3 610 cm-l; T 3.31br (1 H, s, ArH), 5.22(1 H, q, J 6.8 Hz, OCHMe), 6.02 (3 H, s, ArOMe), 7.13br(3 H, s, ArMe), 8.45 (3 H, d, J 6.8 Hz, OC.HMe), and 8.37and 8.67 (each 3 H, s, CMe,).Herqueichrysin Dimethyl Ether.-Treatment of herquei-chrysin (40 mg) with ethereal diazomethane a t 0 "C for 3 hgave the dimethyl ether (42 mg), which crystallised from ben-zene-light petroleum as yellow prisms, m.p. 168-169", [aID + 126" (c 0.6) (Found: C, 68.5; H, 6.15. C,,H,,O,requiresC, 68.75; H, 6.3y0), hIll~ix.222, 268, 349, 394, and 410 nm(log E 4.40, 4.46, 3.92, 4.11, and 4.10); vnULx. (CHC1,) 1600,1 614, 1 634, and 3 320 cm-l; T - 0.16 (1 H, s, exchangeablewith D,O, OH), 3.15 (1 H, s, ArH), 5.45 ( 1 H, q, J 6.5Hz,OCHMe), 5.74, 5.97, and 6.00 (each 3 H, s, ArOMe), 7.05 (3 H,s, ArMe), 8.53 (3 H, d, J 6.5 Hz, OCHMe), and 8.47 and8.69 (each 3 H, s, CMe,).Herqueichrysin Trimethyl Ether. -Treatment of herquei-clirysin (20 mg) with ethereal diazomethane a t room tem-perature for 1 h gave the trimethyl ether, which crystallisedfrom light petroleum as yellow rosettes, m.p. 125-126",[dD +161" (c 0.3) (Found: m/e, 398.1730. C2,H2,06 re-quires M , 398.1729), Anlax. 223, 249, 269, 353infl, 391, and412infl nm (log E 4.31, 4.28, 4.36, 3.95, 4.03, and 3.98); vmax.(CHCI,) 1 605 and 1 628 cm-l; T 3.20 ( I H, s, ArH), 5.46 (1 H,q, J 6.5 Hz, OCHMe), 5.93 and 5.97 (each 3 H, s, ArOMe),6.00 (6 H, s, ArOMe), 7.00 (3 H, s, ArMe), 8.54 (3 H, d, J6.5 Hz, OCHMe), and 8.48 and 8.69 (each 3 H, s, CMe,).Demet~iylherqueiclrr~~in (3a) .-A mixture of herqueichry-sin (60 mg) and pyridine hydrochloride ( 1.5 g) was heatedat 220 "C for 10 min.The mixture was poured into dilutehydrochloric acid and extracted with chloroforni. Re-moval of solvent afforded a yellow powder which waspurified by trituration with chloroform to give demethyl-herqueichrysin (50 mg), m.p. (vacuum-sealed capillary) 250"(initial melting and discolouration), 298-302" (final lique-faction) [lit.,, 250" (decomp.)], [a], +347" (c 0.3) (Found:m/e 342.1106.CI,H,,O, requires M , 342.1103), A,lmx. 220,254, 285infl, 378, and 434 nm (log E 4.44, 4.33, 3.97, 4.04, and4.02) ; v,,,,,. (CHC1,) 1 597, 1 605, 3 430,3 600, and 3 680 cm-1;T (C,D,N) 2.94 ( 1 H, s, ArH), 5.38 (1 H, q, J 7 Hz, OCHMe),6.91 (3 H, s, ArMe), 8.60 (3 H, d, J 7 Hz, OCHMe), and 8.36and 8.62 (each 3 H, s, CMe,).Acetylation with acetic anhydride-pyridine a t room tem-perature for 16 h gave the tetra-acetate as a yellow gum, [&, + 10YO (c 0.2) (Found: m/e 510.1530. C,,H,,OI, requiresM , 510.1526), hIlliLX. 218, 243, 265infl, 350, and 400infl nni(log E 4.38, 4.45, 4.15, 4.10, and 3.82); v,,,~,~. (CHCI,) 1 622arid 1786 cn1-l; 'c 2.83 (1 H, s, ArH), 5.52 (1 H, q, J 7 Hz,OCHMe), 7.06 (3 H, s, ArMe), 7.65 and 7.68 (each 6 H, s,OAc), 8.63 (3 H, d, J 7 Hz, OCHMe), and 8.54 and 8.76(each 3 €3, s, CMe,).2, ( l,l-Dimethylprop-~-enyl)-9-~i~y~r~xy-4-nzethyl-6,7,8-trimethoxyPhenalene-l,3(2H)-dione (7a) .--A solution of9-hydroxy-6,7,8-trimethoxy-4-niethyl-3- (3-methylbut-2-eny1oxy)phenalen- l-one (S), (600 mg) in dimethylformamide( 10 nil) was stirred with anhydrous potassium carbonate (600nig) at 100 "C for 16 11.The mixture was then diluted withwater, neutralised with dilute hydrochloric acid, and extrac-ted with chloroforni. The extract was washed with water,dried, and evaporated under reduced pressure. Chromato-graphy of the residue on a column of kieselgel G (50 g)[ether-benzene ( 1 : 5) as eluant] afforded 2-( 1,l -dimethyl-prop- 2-enyl) - 9- hydroxy- 4-methyl- 6,7,8-trimethoxyphenalene-1,3(2H)-dione (7a) (525 mg, 87%) as a yellow gun1 (Found:m/e, 384.1553.C,,H,40, requires M , %4.1573), hlllRX. 228,261, and 350 nni (log E 4.54, 4.50, and 4.20) ; v,llLLx, (film) 1 603,1674, and 3 355 cn1-l; T - 5.81 (1 H, s, OH), 3.33 ( 1 H, s,ArH), 4.30 (1 H, dd, J t r ( j , j , 17.5, JCls lOHz, CHXH,), 5.13-5.46 (2 H, ni, CH=CH,), 5.94 (3 H, s, OMe), 5.96 (3 H, s,OMe), 6.00 (3 H, s, OMe), 6.53 ( 1 H, s, 2-H), 7.31 (3 H, s,ArMe), and 8.88 (6 H, s, CMe,).Methylation of the Phenalenedione (7a) with Diazojne-thane.-A solution of the dione (7a) (525 nig) in chloroform(15 mi) was treated with an excess of ethereal diazomethanea t room temperature for 30 min.Removal of solvent underreduced pressure left a residue which was chromatographedon a column of lrieselgel G (75 g), using ether-benzene (1 : 5)as eluant, to yield two major fractions. The material ofhigher crystallised from light petroleum to yield2- ( l,l-dimethylprop-2-enyl) -9-hydroxy-4-methyZ-3,6,7,8-tetra-methoxyphenalen-l-one (8b) (130 nig, 24%) as yellow rods,m.p. 121-122" (Found: C, 69.85; H, 6.65%; m/e, 398.1721.C2,H2,06 requires C, 69.3; H, 6.6./,; M , 398.1729),219, 240infl, 265, and 410 nm (log E 4.63, 4.37, 4.23, and4.24); v , , , ~ ~ . 1 630 cm-l; T -8.71 ( 1 H, s, exchangeable withD,O, OH), 3.05 (1 H, s, ArH), 3.40 (1 H, dd, Jtmlss 17.5, Jeih10.5 Hz, CH=CH,), 4.99 ( 1 H, dd, JtrarLS 17.5, J,pl,L 1.5 Hz,CH=CH,H), 5.15 (1 H, dd, J,.is 10.5, Jge,,L 1.5 Hz, CH=CH,H),5.90, 5.94, 5.96, and 6.45 (each 3 H, s, OMe), 7.10 (3 H, s,ArMe), and 8.30 (6 H, s, CMe,).The material of lower R, value crystallised from benzene-light petroleum to afford 2-( 1,l-dimethylprop-2-enyl)-41977methyl-6,7,8,9-tetramethoxyphenalene- 1,3( 2H)-dione (7b) (367mg, 68%) (see footnote * on p.2445) 3s pale yellow crystals,m.p. 119-120" (Found: C, 69.4; H, 6.6%; m/e, 398.1729.C2,H2,06 requires C, 69,35; H, 6.6%; M , 398.1729), A,,,,.222, 255, and 350 nm (log E, 4.44, 4.47, and 4.00) ; v,,,. 1 650and 1 684 cm-l; z 3.28 (1 H, s, ArH), 4.38 (1 H, dd, Jllnns17.5, J c i v 10 Hz, CH=CH,), 5.15-5.50 (2 H, m, CHXH,),5.95and6.02(eachfiH,s,OMe),6.55(lH,s,2-H),7.23(3H,s, ArMe), and 8.92 (6 H, s, CMe,).Methylation of the Phenalenedione (7b) with Methyl Iodideand Silver Oxide.-A mixture of the dione (7b) (100 mg),methyl iodide (15 ml), and silver oxide (300 mg) wasstirred and heated under reflux for 16 h, then cooled, filtered,and diluted with chloroform.The organic solution waswashed successively with dilute aqueous sodium disul-phite and water, dried, and evaporated in vacuo. Theresidue was separated into three compounds by preparativet.1.c. [20 x 20 cm plate, coated with 16 g of kieselgelGF254; ether-benzene (1 : 5 ) as eluant].value gave 2,4-dimethyl-2-(1,1-dimethylprop-2-enyl) -6,7,8,9-tetramethoxyphenalene- 1,3( 2H) -dione (7c) (50 mg, 48%) as white crystals, m.p. 75-76" (frombenzene-light petroleum) (Found: C, 69.75; H, 6.65% ; m/e,412.1879.C24H2806 requires C, 69.9; H, 6.8%; M ,412.1886), Amax. 224, 256, and 356 nm (log E 4.16, 4.56, and3.93); vmx, 1 655 and 1690cm-l; z 3.21 ( 1 H, s, ArH), 4.30The band of higher( 1 H, dd, Jira,l, 17.5, J c i y 10.5 Hz, CH-CH,), 5.26 (1 H, dd,Jlmns 17.5, Jgeln 1.5 Hz, CHZCHtH), 5.33 ( 1 H, dd, JClh 10.5,Jger,& 1.5 Hz, CH=CH,H), 5.90 and 6.00 (each 6 H, s, ORIe),7.19 (3 H, s, ArMe), 8.55 (3 H, s, 2-Me), and 9.03 (6 H, s,CMe,).The band of second highest Rkl value yielded 9,lO-dihytlro-9-iodo- l,2,3,4-tetramethoxy-6,8,8-triniethylphenaleno[ 1,2-blpyran-7-one (9) or 9,l0-dihydro-9-iodo-3,4,5,6-tetrameth-oxy-1,8,8-trimethylphenaleno[1,2-b]pyran-7-one (10) (45mg, 34%) as pale yellow crystals, n1.p.168-170" (fromlight petroleum) (Found: C, 52.4; H, 4.7; I, 24.67;; wz/e,524.0716. Calc. for C,,H,,lO,: C, 52.7; H, 4.8; I, 24.2%;&I, 524.0704), Alllax. 220, 251infl, 268, 354, 390, and 408 nni(log E 4.49, 4.44, 4.53, 4.02, 4.08, and 4.05; vlllax. 1 632cm-l; T 3.10 (1 H, s, ArH), 5.24 (1 H, t, J 6.5 Hz, CHI),5.80 and 5.85 (each 3 H, s, OMe), 5.95 (6 H, s, OMe), 6.45(2 H, d, J 6.5 Hz, CH,CHI), 6.97 (3 H, s, ArMe), and 8.34and 8.59 (each 3 H, s, CMe,).From the band of lowest value was obtained 9,lO-dihydro-9-iodo-3,4,5,6-tetramethoxy- 1,8,8-trimethylphen-aleno[ 1,2-b]pyran-7-one (10) or 9,10-dihydro-9-iodo-1,2,3,4-tetraniethoxy-6,8,8-trimethylphenaleno[ 1,2-b]pyran- 7-one(9) (17 mg, 13%) as a yellow gum (Found: m/e, 524.0709.Calc.for C,,H,5106: M, 524.0704), Amax, 222, 241, 255, 275,285infl, 343, 359, 410, and 426 nm (log E 4.50, 4.36, 4.34, 4.37,4.30, 3.97, 3.92, 3.90, and 3.90); vmax. (film) 1 630 cm-l; T3.19 (1 H, s, ArH), 5.30 (1 H, dd, J 6 and 8 Hz, CHI), 5.85,5.89, 5.96, and 6.00 (each 3 H, s, OMe), 6.50 (2 H , m,CH,CHI), 7.06 (3 H, s, ArMe), and 8.37 and 8.59 (each 3 H,s, CMe,).$kenaleno[ 1,2-b]furan-7-one (Id) .-A solution of the dione(7a) (100 mg) in chloroform (15 ml) was treated with toluene-p-sulphonic acid (200 mg) at room temperature for 1 h, thenwashed successively with aqueous sodium hydrogen carbon-ate and water, dried, and evaporated in vacuo t o yielcl thephenalenofurnnone (Id) (100 mg, 100 yo). This crystallisedfrom light petroleum as yellow crystals, m.p.118-119"(Found: C, 69.35; H, 6.45. C23H2606 requires C, 69.3;8,9-L)ihydro-3,4,5,6-tetramethoxy- 1,8,8,9-tetramethyl-H, 6.6y0), A, 222, 240infl, 255, 275, 283i11f11, 344, 372, 410,and 427 nni (log E 4.51, 4.37, 4.34, 4.37, 4.29, 3.99, 4.01,3.99, and 3.99); vmLx. 1 620 cni-l; T 3.20 (1 H, s, ArH), 5.45(1 H, q, J 6.5 Hz, OCHMe), 5.83, 5.89, 5.94, and 5.95 (each3 H, s, OMe), 7.11 (3 H, s, ArMe), 8.44 and 8.66 (each 3 H, s,CMe,), and 8.54 (3 H , d, J 6.5 Hz, OCHMe).Demethylation of the Phenalenofuranone ( Id) with Hydro-iodic Acid.-The tetramethyl ether (lcl) (70 iiig) as heatedunder reflux for 15 min with aqueous hydriodic acid (55% ;10 ml). The product was filtered off, washed with water,and dried under high vacuum to give (-j)-atrovenetin (55mg, 91 yo) as yellow-orange needles, identical with an authen-tic specimen 5 (i.r., u.v., and n.m.r.spectra, and t.1.c. be-haviour).phenaleno[ 1,2-b]furan- l-one (3b) .-A solution of the phen-alenone (8b) (95 mg) in chloroform (10 ml) was treated withtoluene-p-sulphuric acid (200 mg) a t room temperature for3 h. The mixture was then washed successively withaqueous sodium hydrogen carbonate and water, dried, andevaporated in vacuo. The residue was purified by prepara-tive t.1.c. [20 x 20 cm plate, coated with 16 g kieselgel GFZja;niethanol-chloroform (1 : 19) as eluant] to afford theplzenalenofuranone (3b) (90 mg, 94%) as yellow crystals, m.p.170-171" (from benzene-light petroleum) (Found: C, 69.7;H, 6.7%; m/e, 398.1717.C,,H,,@, requires C, 69.3; H,6.67/,; M, 398.1729), Anlax. 218, 260, 274, 279infl, 393, and414infl (log E 4.59, 4.32, 4.37, 4.34, 4.23, and 4.10) ; v,,,,,, 1 622mi-'; T 2.95 (1 H, s, ArH), 5.26 (1 H, q , J 6.5 Hz, OCHMe),5.88, 5.91, 5.96, and 6.12 (each 3 H, s, OMe), 7.02 (3 H, s,ArMe), 8.40 and 8.62 (each 3 H, s, CMe,), and 8.45 (3 H, d ,J 6.5 Hz, OCHMe).( It)-Demethylherqueichry~in (3a) .-A solution of the phen-alenofuranone (3b) (60 mg) in aqueous hydroiodic acid(55% ; 5 nil) was heated under reflux for 15 min, then cooled,diluted with water, and extracted with chloroform. Theextract was washed with water, dried, and evaporatedin vucuo t o yield ( f)-demethylherqueichrysin (3a) (50 mg,97%) as a yellow powder, identical [i.r.(KCI), u.v., n.m.r.,and t. l.c.1 with authentic ( + ) -demethylherqueichrysin.Demethylation of the Tetramethyl Ether (3b) with PyridineHydrochloride.-A mixture of the tetramethyl ether (3b) (85nig) and pyridine hydrochloride (1.8 g) was heated underreflux for 30 min, then cooled, acidified with dilute hydro-chloric acid, and extracted with chloroform. The extractwas washed with water, dried, and evaporated under reducedpressure to give a yellow powder (41 mg), whichfromitsn.m.r.spectrum and behaviour in t.1.c. was shown t o be a two-com-ponent mixture. The mixture was acetylated with aceticanhydride (4 ml) and pyridine (4 ml) a t room temperaturefor 16 h t o give two tetra-acetates, which were separated bypreparative t.1.c. [ZO x 20 cm plate, coated with 16 g kiesel-gel GF254 ; ether-benzene (1 : 5) as eluant]. From the bandof higher IZF value ( -+) -demethylherqueichrysin tetra-acet'ate (17 mg, 28%) was obtained as a yellow glass, identi-cal (i.r., n.m.r., u.v., and t.1.c.) with authentic (+)-demethyl-herqueichrysin tetra-acetate.The band of lower RF value yielded (&)-atrovenetin tetra-acetate (36 mg, 59y0), which gave yellow crystals, m.p.178-180" (from benzene-light petroleum), identical (i.r.,n.m.r., u.v., and t.1.c.) with authentic (+)-atrovenetin tetra-a ~ e t a t e . ~Prolonged Treatment of Demethylherqueichrysin (3a) withPyridine Hydrochloride.-A mixture of demethylherquei-chrysin (3a) (40 mg) and pyridine hydrochloride (1 g) was8,9-Dihydro-2,3,4,7-tetramethoxy-6,8,8,9-tetrametlzyl2448 J.C.S. Perkin Iheated a t 220 "C for 1 h. The mixture was worked up andthe product acetylated to give, after preparative t.1.c. (de-as in preceding experiment), (+)-demethylherqueichry-sin tetra-acetate (20 mgJ 33%)J -kgl" (c o.2) (identifiedby direct comparison of n.m.r. and U.V. spectra, and t.1.c.behaviour with an authentic sample, [a],, + log"), and (&)-atrovenetin tetra-acetate (18 mg, 30%), identical (n.m.r.,u.v., and t.1.c.) with an authentic spe~irnen.~We thank the S.R.C. for research studentships (to D. A. F.and D. D. H.), and l>r. L. c. Vining for a sample of authenticherqueichrysin.[7,/719 RPceived, 29th April, 1977

ISSN:1472-7781    

DOI:10.1039/P19770002443

出版商:RSC    

年代:1977

数据来源: RSC