1570 J.C.S. Perkin IConstituents of Dragon's Blood. Part 11.l Structure and Oxidative Con-version of a Novel SecobiflavonoidBy LucioMerlini and Gianluca Nasini,' lstituto di Chimica, Centro del C.N.R. per la Chimica delle SostanzeOrganiche Naturali, Politecnico di Milano, 201 33 Milano, ItalyA novel secobiflavonoid, (ZS)-8-trans- [2- (6-benzoyloxy-4-hydroxy-2-methoxy-3-methylphenyl)ethenyl] -5-methoxyflavan-7-01 (1 a) has been isolated from the resin dragon's blood, and identified by spectra and degradativeexperiments. Oxidation of (1 a) or its derivatives with dichlorodicyanobenzoquinone or silver oxide occurs withring closure to give new substituted arylfuro[2,3-h] benzopyrans or 8- (benzofuran-2-y1)flavans. Oxidation of thefurobenzopyran (9b) with hydrogen peroxide-alkali converts the 2-methylphloroglucinol unit into a cyclopent-4-ene-1.3-dione ring.DRAGON'S BLOOD is a commercially available resin, oxyproanth~cyanidins,~ triflavonoids, chalcones,l andusually obtained from trees of Daemolzorops draco terpenoids.5(Palmae) in South-east Asia.2 The resin was investi- We report here the isolation of a novel example of angated by the schools of Brockmann and Robert~on,~ in oxidised biflavonoid (la) by careful t.1.c.of a principalorder to establish the structures of the red pigments fraction from silica gel column chromatography of thedracorhodin and dracorubin. In our hands, however, crude resin. The phenolic nature of (la) is shown by . .the resin has revealed itself as a rich source of other new3 H.Brockmann and H. Junge, Ber., 1943,76,751; A. Robert- substances, flavanS,l biflavonoids? de- son, and W. B. Whallev, [. Chew. Sot., 1950, 1882; H. A.1 Part I, G. Cardillo, L. Merlini, G. Nasini, and P. Salvadori, Olaniyi, J. W. Powell, anh W. B. Whalley. J.C.S. Perkin I , 1973,J . Chem. SOC. ( C ) , 1971, 3967. 179.S. Frankel and E. David, Biochem. Z., 1927,181, 14,6; F. M. L. Merlini and G. Nasini, Communication to the InternationalDean, ' Naturally Occurring Oxygen Ring Compounds, Butter- Symposium on Polyphenols, Gargnano. Italy, 1975.worths, London, 1963, pp. 412 and 491; W. Spaich and G. 5 F. Piozzi, S. Passannanti, M. P. Paternostro, and G. Nasini,Koethke, Deut. Apoth.-Zeit., 1955, 95, 1193. Phytochemistry, 1974, 13, 22311976 1571the easy formation of a diacetate (lb) and a dimethylether (lc).Analytical and spectral data for (la+)agreed with the formula C,H,O, for (la). The presenceof an ester group is shown by the i.r. spectrum,and the n.m.r. spectrum indicates the presence oftwo aromatic methoxy-groups, an aromatic methyl, twoaromatic protons (singlets), the sequence ArCH(O)*CH,*CH,Ar, and twelve aromatic or olefinic protons. Thus(la) must have a skeleton of thirty carbon atoms, whichsuggests a biflavonoid.Treatment of the substance (la) with trifluoroacetic orother acids (Scheme 1) gave a mixture containing theprotons in the n.m.r. spectrum of (la) requires that thesetwo protons must be on different rings. In view of thepresence of an ester group, and of the U.V.absorption of(la) at longer wavelength than that of a simple flavan,lthe other structural unit of (la) must be at an oxidationlevel higher than that of a flavan.Cleavage of the ester group in the dimethyl ether (lc)with lithium aluminium hydride yielded a new phenol(2a). Comparison of spectral data showed that (lc) isa benzoate ester of (2a). It follows that the flavan partof (la) is linked to a nine-carbon unit. This unit musthave an aromatic ring bearing three OR substituents;R O W P hOMet 4 1 a;R:Meb;R:HM: q 0 COP hOMe(11a; R - Hb;R =COMec; R :MeMeMe0(21a;R-Hb; R :Me1 i,OsOLGo*C HO OMe151 (61a;R:Hb ; R:Me(31a; R - Hb; R :MeSCHEME 1two quinone methides dracorhodin (4a) and nordraco-rhodin (4b) ; their formation requires concomitantoxidation, most probably by air.This result indicatesthat, like other components of the resin,ls4 compound(la) is built up from the two flavan units correspondingto (4a) and (4b). In actual fact, the structure (la) con-tains only one flavan unit, as shown by the n.m.r. data,and by the loss of only one unit of mass 104 in the massspectrum (retro-Diels-Alder 6). As both structures (4a)and (4b) contain two meta-substituents on the aromaticring, the presence of two singlets for the aromaticSpectra, Verlag Chemie, Weinheim, 1974, p. 68.S. E. Drewes, ' Chroman and Related Compounds-Masstherefore this ring and the flavan must be linked by a-CH=CH- bridge. Moreover, the n.m.r. data (showingone aromatic proton on each ring) require that thearomatic methyl group must be on the single aromaticring and not on the flavan. These results establish thegross structure of (2a) except for the position of thebenzoate.Confirmation of this structure came fromcatalytic reduction of the methyl ether (2b) to the di-hydro-derivative (3b) ; signals for the new ArCH,*CH,Argroup appeared clearly in the n.m.r. spectrum. Instructures (la) and (2a) and their derivatives, n.m.r.signals for the vinylic protons are always masked by theoverlapping aromatic proton absorption. Conversely1572 J.C.S. Perkin Icleavage of the ester group in (la) by hydride and cata- The mass and U.V. spectra (comparison withlytic reduction of the non-isolated intermediate afforded 2-hydroxy-4,6-dimethoxybenzaldehyde 8, spectra area triphenol (3a), which was easily methylated to (3b).consistent with structure (5). The sequence of theLemieux-Johnson oxidation of the phenol (2a) afforded substituents on the aromatic ring of (5) and thus of (la)two aromatic aldehydes, (5) and (6b), thus confirming and derivatives is also established by the formation ofaldehyde.OMe OMe(7 I 18 Ithe presence of a stilbene double bond. Analytic andspectral data for (6b) are consistent with an 8- or a 6-formyl-5,7-dimethoxyflavan structure. The former wasestablished by the synthesis of (6b) by methylation of thealdehyde (6a), prepared in turn from 5-methoxyfiavan-7-oll via a Gattennann rea~tion.~ Sapport for thisassignment was obtained by reduction (Zn-AcOH) ofthe aldehyde (6a) to 5-methoxy-8-methylflavan-7-01,7the structure of which was established by oxidation with(4a) from treatment of (la) with acid.This latterreaction requires also that the benzoate ester group isortho to the stilbene double bond, as also confirmed byoxidative reactions (see later). We have no evidencesupporting a particular mechanism for the conversion of(la) into (4a) and (4b), although a vinylogous Friesreaction to reconstitute the C,, chain leading to (4a),followed by acid-induced dealkylation of the flavanmoiety and by oxidation in air seems attractive. qj Me0 \ O C O P hOMe( la)R ' R2(9la; COPh H+e'* +e 1. b; H Hc ; C O M e COMed; C O P h MePh \\ ::g;& Ph e; f ; H COPh COMe MeY I g d 1N a o H \ \0 MeOMe(101a; R : Hb; R : MeZ n H * i I3alSCHEME 2dichlorodicyanobenzoquinone 1 to the quinone methide(8) ; the product (8) was different (t.1.c.and n.m.r.) fromthe known 6-methyl isomer, dracorhodin (4a) .lThe other aldehyde (5) was isolated in only a smallamount. However, comparison of the structures (6b)and (2b) requires (5) to be a dimethoxy-methylsalicyl-' A. Robertson, W. B. Whalley, and J. Yates, J . Chem. SOC.,1950, 3117.The configuration of the stilbene double bond of (la)was established as trans by the 100 MHz n.m.r. spectrum,which showed the signal for one of the two protons as adoublet, J 17 Hz.The optical activity of (la) must be due to C-2, whichis the only chiral centre, The 2S-absolute configuration* F.Santavy, D. Walterowa, and L. Hruban, CoZZ. Czech.Chem. Comm., 1972, 87, 18251976 1573was established by hydrogenolysis of the derivative (9b)(see later) with zinc and sulphuric acid to the known(2s) -5-methoxyflavan-7-o1.lThe structure (la) is consistent with biogenesis froma 3,8-linked biflavanoid, by oxidation with cleavage ofthe 2,3-bond. Although no example of a similar struc-ture in nature has been reported so far, in vitro oxidationof a 3-substituted flavonoid with such a cleavage via aBaeyer-Villiger reaction has been achie~ed.~Compound (la) undergoes some interesting oxidationreactions. Treatment with 2,3-dichloro-5,6-dicyano-benzoquinone (DDQ) in benzene gave compound (9a) inhigh yield (Scheme 2). The same reaction most probablyoccurred during attempted methylation of (la) withmethyl iodide and silver oxide, the latter acting as anoxidant to give (Sa), which is immediately methylatedto give (9d).The formation of a monomethyl ether (9d),and of a monoacetate (9f) of (9a) shows that one OHgroup of (la) has taken part in the oxidation reaction.The mass spectrum of (9a) shows a molecular ion a t mie536 [2 mass units less than (la)], and in the n.m.r.spectrum the number of aromatic protons is two lessthan in (la), and a new singlet appears at 6 7.06. Theflavan heterocyclic ring appears unaltered (n.m.r. andmass spectra), as is the ester group, which can be cleaved(LiAlH,) to give the phenol (9b). The 2-arylbenzofuranstructure (9a) is consistent with these data, and with thecourse of similar reactions of 2,2’- and 2,4’-dihydroxy-stilbenes.1° Also the same mechanism should beoperative, i.e. oxidation to a phenoxyl radical, which ismesomeric with a P-carbon radical, followed by radicaladdition to the double bond or by nucleophilic additionof the ortho-OH to the quinone methide system of theradical, and oxidation to the benzofuran.1°However if (la) is treated with methanolic potassiumhydroxide in order to hydrolyse the ester group, theisomer (loa) of (9b) can be isolated, together withbenzoic acid.Again the mass and n.m.r. spectra andthe formation of a dimethyl ether (lob) indicate that(lOa) has a 2-arylbenzofuran nucleus, and the onlypossible structure is the one shown. In this case it mustbe the new ortho-OH formed by hydrolysis of the benzoate(la), which is involved in cyclization, rather than the 7-OHof the flavan.Confirmation of this hypothesis camefrom synthesis of (lob) by oxidation (Ag,O) of (2a), inwhich all the OH groups except for that in position 6’are protected by methylation. In this latter case adirect redox addition of the phenoxyl radical to thedouble bond must be invoked.ll Compound (lob) isidentical with the monomethyl ether of (loa) (t.1.c. andspectral comparison). Moreover, direct conversion of(9b) into the isomer (loa) could be achieved, although inlow yield, by treatment with zinc and acid. Undermore forcing conditions, hydrogenolysis of the benzo-furan ring occurred, with formation of (3a).Another unusual oxidation reaction was observedwhen the benzofuran (9b) was treated with hydrogenperoxide in alkaline medium (Scheme 3).Of the twomain products, one was easily identified as furobenzo-pyrancarboxylic acid (Ha), derived from complete”*+ ! / “’I1121 a; R = H6; R:Me(131 (141 a; R = Hb; R-COMeSCHEME 3oxidation of the dihydroxy-substituted aromatic ring of(9b). The other product (ll), C,,H,O,, is a yellowsolid, with strong carbonyl i.r. bands at 5.80 and 5.90pm and a highly conjugated chromophore. The n.m.r.spectrum indicates that whereas the furobenzopyran unithas not changed, the ‘ upper ’ part of the molecule haslost two carbon atoms. One is that of the methoxy-group, whereas the vinylic methyl group (uncoupled inthe n.m.r.) is still present.Methylation (MeI-K,CO,)of (11) introduced two geminal methyl groups. Thisresult, combined with the presence of a CH, singlet a t6 2.98 in the n.m.r. spectrum of (ll), can be explained interms of double alkylation of a *CO-CH,*CO* system.All the available evidence is consistent with the struc-tures (11) and (13), which are further confirmed byreduction (NaBH,) of (13) to the hexahydro-diol (14a).The main features of the spectrum of this product are amethyl doublet at high field, a signal for a new benzylicproton (1’) with two vicinal couplings, and doublets forthe two CH.0. units, coupled with H-1’ or H-5’, andboth shifted a t lower field by acetylation [to (14b)I.The formation of cyclopent-4-ene-1 ,&diones by oxidationof orcinol derivatives to o-quinones, followed by ringcontraction due to a benzylic rearrangement, has beenreported.lZ However, this mechanism cannot apply inthe oxidation of (9b), as the only free position foroxidation and formation of the quinone is 3‘.Thereforeone would expect that the ring contraction takes placebetween C-2’ and -3’or C-3’ and -4’ (Scheme 4). On thecontrary, the structure of the oxidation product (11)implies the demethylation of the 6’-OMe, followed byring contraction between C-1‘ and -5’ of (9b). Anattractive mechanism for the reaction is that alreadv dL. Jurd, Tetrahedron, 1966, 22, 2913.lo B. Cardillo, M. Cornia, and L. Merlini, Gazzetta, 1975, 105, 11 F. Minisci, Accounts Chem. Res., 1975, 8, 165.12 R.K. Haynes and H. Musso, Ckem. Bey., 1974, 107, 3723. 11511574 J.C.S. Perkin Iproposed l3 for tetraphenylresorcinol, which involvesoxidation to a diradical (on C-1' and -5' in this case),followed by coupling and extrusion of CO. The form-ation, however, of a labile colourless compound in ourreaction which is quickly converted into the yellow (11)QMe(9blOMeSCHEME 4by treatment with acid suggests the following sequence :hydrolysis of the 6'-OMe group, followed by oxidation ofthe 1',6'- or 5',6'-double bond with cleavage to give thetautomer of a 1,2,4-triketone, which could condense togive an aldol, in turn easily dehydrated to (11) in acidicmedium (Scheme 5 ) .1111 3-- R' OQ-:2OHSCHEhlE 5Compounds (15) and (16), related to both (9) and (13)have been found in the plant Myricn gaZe,14 where anoxidation process similar to that observed by us couldy p J P hMe MeOH 0 0115) 1161occur.Oxidation of 4,6-dihydroxy-Z-me t hox y-3-me t hyl-dihydrochalcone with alkaline hydrogen peroxide orsodium hydroxide in an attempt to obtain a derivativeof (16) was, however, unsuccessful.13 H. Giisten, G. Kirsch, and D. Schulte-Frohlinde, Tetrahedron,1968,24,4393.EXPERIMENTALU.V. spectra were measured for solutions in 95% ethanolwith a Beckman DK-2 apparatus; n.m.r. spectra wereobtained with a Varian A-60 or XL-15-100 instrument.Unless otherwise stated, column chromatography wasperformed with Merck silica gel (0.05-0.20 mm) and t.1.c.with Merck silica gel HF,,4.Isolation of the Secobiflavonoid (la) .-Powdered commer-cial dragon's blood resin (200 g) was mixed with 100 g ofsilica gel, and placed on a silica gel column.After elutionwith hexane, increasing amounts of ether were added to theeluant; with hexane-ether (1 : 1) a complex mixture wascollected. Preparative t.1.c. (benzene-ether, 4 : 1) gave(2s) -8-trans-[ 2- (6-benzoyZoxy-4-hydroxy-2-nzetJ~oxy-3-nzethyZ-~henyZ)ethenyZ]-5-methoxyflavan-7-oZ (la), which was de-tected on t.1.c. plates by spraying with cerium(1v) sulphatein sulphuric acid (brown colour on heating); RF 0.43 inether and 0.15 in benzene-ether (9 : 1) on Bakerflex IB-Fplates. Compound (la) has m.p. 115-118" (from ether-hexane), [CC],,~~ -60' (c 0.57 in CHCl,), vn/e 538, A,,,.232.5,316, and 326sh nm (E 31 000, 24 900, and 24 300), A,,,(CHCl,) 3.0 (OH) and 5.8 pm (OCOPh), 6 (CDCI,) 2.10 (s,Me), ca. 2.0 (m, H,-3), ca. 2.6 (m, H,-4), 3.56 and 3.70(OMe), 4.90 (X of ABX, PhCHO), 6.04 (s, H-6), 6.38 (s,H-57, 6.97 (1 H, J 17 Hz), 7.1-8.2 (11 H), and 6.8-7.1 (2OH).Acidic Degradation of the Secobi$avonoid (la) .-Compound(la) (250 mg) was dissolved in trifluoroacetic acid (8 ml)and kept at room temperature for 20 h. Evaporation andchromatography with chloroform-ether gave compounds(4a) (35%) and (4b) (lo%), identified by t.1.c. comparisonand n.m.r. spectra.lThe Diacetate (lb).-Acetylation of (la) (100 mg) [Ac,O(5 ml) and AcONa (100 mg) at 60 "C for 30 min] gave thediacetate (lb) as a glassy solid, -47.5" (c 0.19 inMeOH), m / e 622, Amax.230sh, 289sh, and 316 nm (E 31 300,12 800, and 15 loo), Amx. (alkaline EtOH) 346 nm (c 16 200),Anlax. (Nujol) 5.68 (OCOMe) and 5.75 pm (OCOPh), 6 (CDCl,)2.01 (Me), 2.14 and 2.20 (Ac), 1.84-2.10 (H,-3), 2.59 (m,Ha-4), 3.50 and 3.67 (OMe), 4.84 (H-2), 6.17 ( s , H-6), 6.68( s , H-57, 7.1-7.5 (10 H), and 7.9-8.0 (2 H).The Dimethyl Ether ( lc) .-Compound (la) was methylated(CH,N2-Et,O for 1 week) to give the dimethyl ether (lc) aswhite crystals, m.p. 179" (from ether) (Found: C, 73.55;H, 6.2. C,,H,,O, requires C, 74.2; H, 6.05y0), m/e 566,Amax. 234, 318, and 326sh nm (E 32 400, 26 008, and 25 700),h,,, (KBr) 5.78 pm (OCOPh), 6 [CDCl,-(CD,),CO (2 : l)] 2.12(Me), 2.0-2.2 (H,-3), 2.5-2.7 (H2-a), 3.52 and 3.54 (OMe),3.82 (2 OMe), 4.97 (H-2), 6.10 (s, H-6), 6.54 (s, H-5'), and7.3-8.2 (12 H ) .The Phenol (2a).-A solution of the dimethyl ether (lc)(200 mg) in dry ether was refluxed for 0.5 h with an excessof lithium aluminium hydride.Treatment with water anddilute acid, extraction with ethyl acetate, and preparativet.1.c. [hexane-AcOEt (2 : 1)J gave the phenol (2a) as aglassy solid, vn/e 462(100%), 358(37), 343(28), 283(6),179(37), and 108(3), 6 (CDC1,) 1.90 (Me), 1.8-2.2 (H,-3),2.64 (H,-4), 3.42, 3.66, 3.76, and 3.78 (OMe), 5.05 (H-2),6.12 (s, H-6), 6.26 (s, H-57, and 7.0-7.6 (7 H).The Per-0-methyl Derivative (2b) .-The phenol (2a) wasmethylated as described for (la), to give the penta-methoxy-l4 T. Anthonsen. I. Falkenberg, $3. Laake, A. Midelfart, and T.Mortensen, Acta Chem.Scand., 1971, 25, 19291976compound (2b), m.p. 118", m/e 476(100%), 372(28), and357(33), Amax. 306 and 329sh nm (E 15 400 and 10 600).The TviphenoZ (3a) .-(a) From the secobiflavonoid (la).The reduction product (2a) (not isolated) was hydrogenatedin ethyl acetate over 10% palladium-carbon.(b) From the benzofuran (loa). A solution of (loa) (50mg) in methanolic 10% sulphuric acid was refluxed for 15 hwith an excess of zinc powder. The reaction was monitoredby t.1.c. Evaporation, treatment with aqueous sodiumcarbonate, extraction with ether, and preparative t.1.c.gave the triphenol (3a) as a glassy solid, m/e 436, a;t, 280nm (E 3 580), A,=. (alkaline EtOH) 290 nm (E 8 000), 8[(CH,),CO] 2.0 (Me), 1.9-2.2 (H,-3), 2.5-2.8 (H,-4 andArCH,CH,Ar), 3.57 and 3.73 (OMe), 5.03 (H-2), 6.15 and6.27 (s, H-5' and H-6), 7.3-7.6 (5 H), 7.71 (OH), and 7.81(2 OH).The Pentavnethoxy-compound (3b) .-Reduction of (2b)over 1 Oo/o palladium-carbon in ethyl acetate or methylationof (3a) with methyl iodide-potassium carbonate in acetonegave the methyl ether (3b), m.p.120", -42" (c 0.52 inCHCl,) (Found: C, 72.55; H, 7.5. C29H3406 requires C,72.8; H, 7.15y0), m/e 478(68y0), 284(90), 283(100), 209(95),195(100), 179(18), 165(68), and l04(59), 6 (CDCl,) 2.03 (Me),2.0-2.2 (H,-3), 2.6-2.9 (H,-4), 2.78 (ArCH,-CH,Ar), 3.503.55, 3.74, 3.80, and 3.82 (OMe), 4.92 (H-2), 6.10 and 6.15(H-5' and H-6), and 7.15-7.5 (5 H).(2s) -7-Hydroxy-B-rnethoxyjlavan-8-ca~baZde?zyde (6a) .-Compound (6a) was synthesized as reported from (2S)-5-methoxyflavan-7-01 and had m.p.125", m/e 284(47%),193(100), 152(33), and 104(53) (Found: C, 71.8; H, 5.8.C17HlGO4 requires C, 71.8; H, 5.65%), -97.5" (c 0.53in CHCI,), A,,,. 296 and 330sh nm ( E 19 500 and 3 840), 6(CDCI,) 7.45 (s, ArCHO).Oxidation of the Phenol by Osmium Tetraoxide.-Osmium tetraoxide (100 mg) dissolved in dry ether wasadded dropwise t o a stirred solution of (2a) (30 mg) in drydioxan (5 nil) ; the reaction was monitored with t.1.c. untilthe starting material had disappeared, then water (2 ml)and an excess of potassium periodate were added, andstirring was continued for 20 min. Evaporation, dilution,extraction with ether, and preparative t.1.c. with hexane-ethyl acetate (2 : 1) gave 6-hydroxy-2,4-dimethoxy-3-methylbenzaldehyde (5), Amax.231, 236sh, 286, and 330 nm,?n/e 196(100~o), 181(41), 178(42), and 150(76); and (2s)-5,7-dimetlioxyflavan-8-carbaldehyde (6b), m.p. 95-loo",m/e 298(48%), 207(100), 194(71), and 136(38), La, 229,290, and 320sh nm (E 12 700, 12 400, and 4 000), identical(t.1.c. and mass and n.m.r. spectra) with a specimenobtained by methylation of (6a) (MeI-Ag,O in Me,CO for0.5 h at reflux).(2s) -5-Methoxy-8-methyZj?avan-7-oZ (7) .-Prepared from(Ga) by the reported method, the jlavanol (7) had m.p.140-143' (Found: C, 75.65; H, 6.95. C1,H1,O, requiresC, 75.55; H, 6.7%), vn/e 270. Oxidation of (7) with 2 mol.equiv. of UDQ in benzene at reflux for 2 h gave the quinonemethide ( 8 ) , m.p.170", m/e 266(44%), 251(100), 223(6),181(6), and 152(8), A,, 272, 320, 330sh, 378, and 500 nm(E 11 000, 8 500, 7 200, 4 450, and 6 700).(2s) - 8- (2-BenzoyZoxy-4-hydroxy-5-methyZ-6-nzethoxy~henyZ) -3,4-dih ydro-5-methoxy-2-fiIzenyZ-2H- furo [2,3-h] - l-benzopyran(9a).--A solution of the secobiflavonoid (la) (500 mg) indry benzene (30 ml) was treated with an excess of DDQ, andstirred for 1 h at room temperature. Filtration, evapor-ation, and preparative t.1.c. gave the furobenzopyran (9a)(50%), m.p. 120°, [a]D20 -52" (c 0.40 in CHCl,) (Found:1575C 73.1; H, 5.35. C,,H,& requires C, 73.85; H, 5.25%),m/e 536, 432 (M - 104), 328, 327 (432 - 105), 300, and284, Lx 286sh and 305 rim (E 9 900 and 10 800) , LX. (alk-aline EtOH) 320 nm (E 10 600), &, (Nujol) 3.0br (OH) and5.75 pm (OCOPh), 6 (CDC1,) 2.14 (Me), 2.0-2.3 (H-3),2.70 (m, H,-4), 3.62 and 3.66 (OMe), 5.09 (X of ABX, H,-2),6.09 (s, H-37, 6.55 (H-6), 7.06 (s, H-9), and 7.3-8.2 (10 H).The Diphenol (9b) .-A solution of the furobenzopyran(9a) (100 mg) in ether was treated with lithium aluminiumhydride in the usual way, and gave the diphenol (9b) as aglassy solid, m.p.63-65", m/e 432, A,,, 256.5, 287sh, 300,308sh, and 330sh nm ( E 8 000, 11 700, 12 500, 12 400, and7 200), 8 (CDCl,) 2.12 (Me), 2.0-2.4 (H,-3), 2.65-2.95(Hz-~), 3.60 and 3.82 (OMe), 5.10 (H-2), 6.25 (s, H-3'), 6.62(s, H-6), and 7.14 (s, H-9), 6 [(CH,),CO] 2.11 (Me), 3.58 and3.84 (OMe), 4.64 (OH), 5.16 (H-2), 6.20 (s, H-3'), 6.77 (s,H-6), 6.95 (s, H-9), and 7.2-7.6 (5 H).Hydrogenolysis of the DiphenoZ(9b) .-To the diphenol (9b)(150 mg) dissolved in methanol 10% sulphuric acid (8 ml)an excess of zinc was added, and the mixture was refluxedfor 20 h.The usual work-up and preparative t.1.c. gave8-ethyl-5-methoxyflavan-7-01 and (2S)-5-methoxyflavan-7-01, identified by mass and n.m.r. spectra and optical rot-ati0n.lThe Diacetate (9c) .-Acetylation [Ac,O-pyridine] of thediphenol (9b) gave the diacetate (Sc), m.p. 155-157", m/e516(90%), 474(38), 432(24), 370(75), and 328(100), A,,(Nujol) 5.70 prn (OCOMe), 6 (CDC1,) 2.12 (Me), 2.20 and2.30 (Ac), 2.0-2.8 (4 H), 3.60 and 3.86 (OMe), 5.13 (H-2),6.65 and 6.75 (H-3' and H-6), 7.05 (s, H-9), and 7.20-7.60The Methoxy-benzoate (9d) .-A solution of the secobi-flavonoid (la) (250 mg) in acetone was refluxed for 10 hwith methyl iodide (1.5 ml) and silver oxide (250 mg) .Theusual work-up and t.1.c. afforded the methoxy-benzoate (9d)[which was also prepared quantitatively by treating (9a)(400 mg) with methyl iodide-potassium carbonate inacetone] as pale yellow crystals, m.p. 80-85", m/e 550(53%),446(35), 341(5), 313(15), 298(13), and 105(100), ha, 306 nm(& 3 300), Lax. (CHC1,) 5.8 pm (OCOPh), 6 (CDCI,) 2.20 (Me),1.9-2.9 (4 H), 3.62, 3.66, and 3.85 (OMe), 5.10 (H-2), 6.10(s, H-3'), 6.62 (s, H-6), 7.05 (s, H-9), and 7.2-8.3 (10 H).The Methoxy-phenol (9e) .-The methoxy-benzoate (9d)was treated with lithium aluminium hydride as describedabove to give the phenol (9e) as a glassy solid, m/e 446, 6(CDCl,) 2.12 (Me), 3.64, 3.72, and 3.88 (Ohle), 5.17 (H-2),6.50 (s, H-6), 6.70 (s, H-3'), and 7.20 (s, H-9).The Acetate (9f) .-The hydroxy-benzoate (9a) was acetyl-ated [Ac,O-pyridine] to give the acetate (9f) as a glass, 6(CDCI,) 2.17 (Me), 2.33 (Ac), 3.64 and 3.67 (OMe), 5.10(H-2), 6.14 (s, H-3'), 6.92 (s, H-6), and 7.15 (s, H-9) (theassignment of the two last signals is based on the nuclearOverhauser effect between 5-OMe and H-6 in benzene solu-tion).(2S)-8- (6-Hyd~oxy-kmetboxy-5-methylbenzofuran-2-yl) -5-methoxyjlavan-7-0Z(lOa) .-The secobiflavonoid (la) (200 mg)in methanolic 2~-potassium hydroxide (10 ml) was heatedfor 30 min on a steam-bath; dilution, acidification, extrac-tion with ether, and preparative t.1.c.gave benzoic acid andthe benzofuran (loa), m.p.215-218" (from ether), m/e432(95%), 328(100), 313(55), 299(4), and 164(31), A,,310sh, 320, and 333sh nm (E 22 300, 25 400, and 16 800).(alkaline EtOH) 332 nm ( E 13 SOO), 6 [(CD,),CO] 2.10(Me), 2.0-2.2 (H,-3), 2.70 (m, H,-4), 3.50 and 3.80 (OMe),(5 H).5.05 (H,), 6.20 (s, H-6), 6.80 (s, H-7'), 7.05 (s, H-3'), 7.2-7.1576 J.C.S. Perkin I(5 H), and 8.25 (OH). A few mg of (loa), identified by U.V.spectrum and t.1.c. comparison, were also obtained bytreatment of (9b) (10 mg) with zinc in methanolic 5%sulphuric acid for 30 rnin a t reflux.The Methyl Ether (lob).-Treatment of the phenol (2a)with silver oxide in acetone for 1 h at reflux, or methylationof (lOa) with diazomethane, yielded the methyl ether (lob),m.p.75-83', m/e 460(70%), 341(35), 283(5), and 178(24), Lx 320sh and 332 nm (E 18 000 and 20 000), 6 (CDCl,)2.16 (Me), 2.1-2.3 (Hz-~), 2.75 (H,-4), 3.82, 3.88, and 3.92(OMe), 5.08 (H-2), 6.15 (s, H-6), 6.75 (s, H-7'), 6.90 (s, H-3'),and 7.2-7.4 (5 H).(2s) -5-Methoxy-8- (2-nzethyZ-3,5-dioxocycZopent- l-enyZ)-3,4-dihydro-2-$henyZ-2H-furo[2,3-h]- 1-benzopyran (1 1) .-Thefurobenzopyran (9b) (300 mg) was added to a stirred solu-tion containing methanolic N-potassium hydroxide (20 ml) ,water (2 ml), and hydrogen peroxide (1 ml) during 10 minat room temperature. Dilution, treatment with dilutehydrochloric acid, and extraction with chloroform gave amixture which was separated on a column of silica gel (chloro-form-methanol as solvent).Elution with CHC1,-MeOH(100 : 1) gave compound (1 1) ; use of a ratio of 100 : 50 gavecompound (12a) (see below) and a ratio of 50 : 50 gave a fewmg of a very polar compound which on acidification with con-centrated hydrochloric acid gave compound (1 1). ThecycZopentenedione (1 1) formed yellow crystals, m.p. 228-232'(Found: m/e 388.1281 f 0.004. C,,H,,O, requires M,388.1311), Lx. 267.5, 279sh, and 407 nm (E 14 200, 11 850,and 22 000), A,, (alkaline EtOH) 270sh, 297, and 500sh nm(E 8 900, 13 200, and 2 500), Amx (Nujol) 5.8 and 5.9 pm (COconj.), 6 (CDCl,) 2.24 (m, H,-3), 2.46 (Me), 2.77 (m, H2-a),2.98 (s, CO*CH,CO), 3.87 (OMe), 5.15 (H-2), 6.60 (s, H-6),7.90 (s, H-9), and 7.35-7.50 ( 5 H).The dimethyl derivative ( 13). The cyclopentenedione(150 mg) was refluxed for 2 h with methyl iodide (0.5 ml)and potassium carbonate (200 mg) in dry acetone (20 ml) .Filtration, concentration, and precipitation with ether gavethe dimethyl derivative (13), m.p.223-225', m/e 416(66%),312(100), and 297(10), 268.5, 277sh, and 410 nm (E14 200, 12 500, and 23 400), Amx. (Nujol) 5.8 and 5.9 pm(CO conj.), 6 (CDCl,) 1.18 (s, CMe,), 2.42 (Me), 2.0-2*.3 (m,H,-3), 2.6-2.8 (H,-4), 3.82 (OMe), 5.08 (H-2), 6.57 (s, H-6),7.92 (s, H-9), and 7.2-7.5 (5 H).The hexahydro-diol (14a). The dione (13) (200 mg) wasreduced with methanolic sodium borohydride ; the usualwork-up gave the diol (14a), m.p. 80-83', vn/e 422(99%),318(100), 216(31), 198(99), and 98(36), Am= 258, 264sh,298, 306, and 320 nm (E 18 150, 15 500, 1980, 1590, and1390), 6 (CDCl,) 1.02 and 1.12 (Me), 1.22 (d, CH-CH,, J7.0 Hz), 2.08-2.90 (H2-3, H,-4, and H-1'), 3.10 (H-5', JJ 4 t , ~ ' 5, J1#,st 11 Hz), 3.30 and 3.80 (d, HCOH), 3.82 (OMe),5.09 (H-2), 6.59 and 6.61 (s, H-6 and H-9), and 7.26-7.50Acetylation of the diol (14a) (150mg) with pyridine and acetic anhydride gave the diacetate,m.p. 55-60", 6 (CDCl,) 0.94 and 1.22 (Me), 1.14 (d, Me),1.88 and 2.11 (Ac), 2.0-2.8 (H,-3, H,-4, and H-1'), 3.19(H-59, 3.83 (OMe), 5.12 and 4.66 (d, H-4' and 2'), 5.10(H-2), 6.51 and 6.59 (s, H-6 and H-9), and 7.3-7.5 ( 5 H).(2s) -3,4-Dihydro-5-rnethoxy-2-phenyl-2H-fur0[2,3-1~]- 1-benzopyran-8-carboxylic acid (12a) had m.p. 300' (decomp.),m/e 324, Lx. 288 and 299sh nm (E 13 300 and 1 400). Themethyl ester (12b) (made with diazomethane) had m.p.160-162O, w/e 338(34%) and 234(100), 6 (CDCl,) 3.85 and3.80 (OMe), 6.84 (s, H-6), and 7.54 (s, H-9).(5 H).The diacetate (14b).We thank Mr. E. Barlesi for technical help.[6/213 Received, 2nd February, 197610 Copyright 1976 by The Chemical Societ
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