Flavan derivatives. XVIII. Synthesis of hemiketals containing the peltogynol ring system: 3(3')-Hydroxyisochromano (4',3':2, 3) chromans. Conversion of 2'-hydroxychdcones into flav-3-enes and its biosyntheticimplications

Abstract

Reduction of three 1?-oxoisochromeno(4?,3?:2,3)chromones [chromeno(3?,2?: 3,4)isocoumarins] with lithium aluminium hydride has been shown to yield 3(3?)-hydroxyisochromano(4?,3?:2,3)chromans (hemiketals). The structures of these compounds (the 7-methoxy, 7,6?,7?-trimethoxy, and parent hemiketals) were unequivocally established by N.M.R., mass spectral, and chemical data. The hemiketals contain the peltogynol ring system, and one of them is the 7,6?,7?- trimethyl ether of the structure originally proposed for this leucoanthocyanidin by Robinson and Robinson. The hemiketals were obtained as mixtures of cis- and trans- isomers which underwent equilibration in deuterochloroform or in wet chloroform, and configurations were assigned to the isomers from a detailed study of their N.M.R. spectra. The hemiketals suffered dehydration when heated further in deuterochloroform, and gave the isochromeno(4?,3?:2,3)chromens (flav-2-enes), which immediately gave the flavylium salts with cold acids in air. The flavylium salts were also formed very readily from the hemiketals and acid, and the trimethoxy- henliketal gave the peltogynidin trimethyl ether cation. In connection with the mechanism of formation of the hemiketals from chromenoisocoumarins it was found that 2?-hydroxychalcones are reduced by sodium borohydride to flav-3-enes, and these readily give anthocyanidins when treated with acid. Parallel biological reduction of chalcones is clearly possible and a plausible, new, biosynthetic pathway leading directly from 2?-hydroxychalcones to anthocyanidins and catechins is proposed. Flav-3-enes are valuable intermediates for preparation of flavans, flavan derivatives, and flavylium salts, and the new synthesis makes flav-3-enes readily accessible in one stage from 2?-hydroxychalcones.

13C-Labelled (±±)-Catechin From Potassium [13C]Cyanide

“…Flavan-3,4-diol (12) was synthesized in 58% yield in three steps from 9 by the Clark-Lewis method (Scheme 2): [18,19] borohydride reduction of 9 and Lewis acid catalyzed cyclization into racemic flavene 11, which was then directly transformed by an osmium-catalyzed dihydroxylation into 12 with high diastereoselectivity (the all cis-isomer was not observed in our hands). As expected, [19,20] 11 was a very labile compound that could not be purified.…”

“…Synthesized from 188 mg of 11 by the Clark-Lewis method [18] modified by Kawamoto et al [19] Yield: 112 mg of the 2,3-trans-3,4-cis diol 12 (58% from 9). -1 H NMR [19] …”

Total synthesis of asymmetric flavonoids: the development and applications of 13C-labelling

“…Reduction of hydroxychalcone 40 using NaBH 4 followed by BF 3 -OEt 2 catalysed ring closing provided chromene 42 (Clark-Lewis method [41,42], Fig. 11).…”

Synthesis of high molecular mass condensed tannin by cationic polymerization of flavan 3,4-carbonate

“…All these starting monomers were obtained from natural products, 8 by reduction of taxifolin or by oxidation of flav-3-ene. 9 It is impossible to obtain flavan-3,4-diols with all possible hydroxylation patterns of the A-and B-ring, from natural products, for the preparation of condensed tannins.…”