摘要:

CHEMICAL COMMUNICATIONS, 1968 1557 Synthesis of Haernocorin Aglycone By B. LAUNDON and G. A. MORRISON* (Department of Ovganic Chemistry, The University, Leeds 2) THE plant glycoside haemocorin is one of a small group of natural products which have structures based on the phenalenone nucleus. Other mem- bers of this group are atrovenetin,l herqueinone,l and resistomycin ;2 dimeric variants are also known, e.g. duclauxin.3 Degradative studies have re- realed that haemocorin aglycone is to be repre- sented by the structure (XI; R1 = R2 = H) or the tautonieric form (XII; R1 = R2 = H).4 Because of the possibility of tautomerism, haemocorin aglvcone affords two monomethyl ethers, A (XI ; It1 = Me, R2 = H) and B (XII; R1 = Me, R2 'H) and two dimethyl ethers, A (XI; R1 = R2 = Me) and B (XII; R1 = It2 = Me).Here we describe the synthesis of the two dimethyl ethers. lye have also obtained the third possible mono- methyl ether of the aglycone, hitherto unknown, which has the structure (XI ; K1 = H, R2 = Me) or R = Me) and the latter was lithiated, with n-butyl-lithium. Treatment of the lithio-deri- vative with methyl borate followed by oxidation with hydrogen peroxide6 gave a mixture of 2,7-dimethoxynaphthalene-3,6-diol (11) and 2,i-di- methoxy-3-naphthol (111) which were obtained pure in yields of 43% and 21qb respectivelv. Alethylation of the dihydric phenol (11) afforded the symmetrical tetramethoxynaphthalene (117 lvhich was converted into the aldehyde (IT) in 60°, yield by means of a Vilsmeier reaction. The aldehyde (V) was converted in quantitative yield into the unsaturated acid (VI: R = H) by first treating it, in a Wittig reaction, with ethoxycarbonylmethyl- enetriphenylphosphorane, and then saponif!-ing the ester (VI ; R = Et) thus obtained.Hydrogenation of the acid (VI) gave the tetramethoxynaphthalene- propionic acid (VII) (8776 yield). (VIII) the tautomeric form (XII; K1 = H, R2 = Me). Since the dimethyl ether A has previously been hydrolysed to the a g l y ~ o n e ~ ~ the sequence described below permits the synthesis of haemocorin aglycone itself, which thus becomes the first naturally occurring phenalenone to be obtained by synthesis. :3,6-Dibromonaphthalene-2,7-diol (I ; R = H)5 was converted into its dimethyl ether (I; Cyclisation of (VII) to give the tetramethoxy- phenalanone (VIII) in 58% yield was achieved with polyphosphoric acid.Addition of phenyl- magnesium bromide to compound (VIII) proceeded quantitatively to give the carbinol (IX), which was dehydrated to give 4,5,8,9-tetramethoxy-3-phenyl- phenalene (X) in a yield of 777; after purification. The structure of the phenalene (X) followed from1558 CHEMICAL COMMUNICATIONS, 1968 its n.m.r. spectrum: 3-proton singlet a t T 6.91 (4-OMe group); 6-proton singlet at 6.14 and 3- proton singlet a t 6-07 (5,8,9-OMe groups) ; 2-proton doublet at 6.11, J 4.5 c./sec. (CH,) ; l-proton triplet a t 4.07, J 4.5 c./sec. (2-H atom) ; l-proton singlets at 3.14 and 3.09 (aromatic H atoms); 5-proton singlet a t 2-72 (Ph). When the phenalene (X) was hydrolysed by being heated with aqueous methanolic hydrochloric acid and the crude product was dehydrogenated with 2,3-dichloro-5,6-dicyanobenzoquinone a mixture of haeniocorin aglycone dimethyl ethers A (XI; R1 = R2 = Me) (8% yield) and B (XII; Iil = R2 = Me) (2006 yield) was obtained which was separated by preparative layer chromatography on Kieselgel.Acid hydrolysis of either of the dimethyl ethers gave initiallj- a violet-coloured phenol which, from its n.m.r. spectrum, contained two methoxy- groups. Upon methylation it gave a mixture of dimethyl ethers A and B, and we have accordingly designated it as the aglycone monomethyl ether C (XI; R1 = H, R2 = Me) or the tautomeric form (XII; R1 = H, R2 = Me). Monomethyl ether C afforded two monoacetates which are tentatively assigned structures (XI; R1 = Ac, R2 = Me) and (XII; R1 = Ac, R2 = Me) on the basis of the acetoxy-group methyl signals which appear in their n.m.r.spectra a t T 7-53 and 8-53 respectively. Satisfactory analyses and spectra were obtained for all the new compounds described. We are indebted to Dr. R. Thomas of Imperial College, London, for kindly providing us with authentic samples of haemocorin aglycone and its methyl ethers for purposes of comparison. (Received, September 26th, 1968; Corn. 1314.) D. H. R. Barton, P. De Mayo, G. A. Morrison, W. H. Schaeppi, and H. Raistrick, Tetrahedron, 1959, 6, 48; G. A. Morrison, I. C. Paul, and G. A. Sim, Proc. Chem. SOC., 1962, 352; I. C. Paul and G. A. Sim, J . Chern. Soc., 1965, 1097. N. A. Bailey, C. P. Falshaw, W. D. Ollis, M. Watanabe, M. M. Dhar, A. W. Khan, and V. C . Vora, Chem. Comm., 1968, 374. S. Shibata, Chem. in Britain, 1967, 3, 110. 4 ( a ) R. G. Cooke and W. Segal, Austral. J . Chern., 1955, 8, 107; (b) idem., ibid., p. 413; (c) R. G. Cooke, B. L. Johnson, and W. Segal, ibid., 1958, 11, 230. R. G. Cooke, B. L. Johnson, and W. R. Owen, Austral. J . Chem., 1960, 13, 256. Cf. 31. F. Hawthorne, J . Org. Chem., 1957,22, 1001.

ISSN:0009-241X    

DOI:10.1039/C19680001557

出版商:RSC    

年代:1968

数据来源: RSC