Synthesis of biflavonoids in which the flavan units are linked through oxygen from C-2 to C-3 or C-4

Abstract

Flav-2-enes [e.g.(1)] have been utilised via 2,3-cis-2-acetoxy-3-bromoflavans for the synthesis of C-2–O–C-3- and C-2–O–C-4-linked biflavonoids. For example, 2,3-cis-2-acetoxy-3-bromoflavans [e.g.(19)] react with (±)-tetra-O-methylcatechin (18) to give 2,3-cis-3-bromo-2-(2,3-trans-3′,4′,5,7-tetramethoxyflavan-3-yloxy)flavans (21) and (23) which have been converted into 3,4-cis-2-(2,3-trans-3′,4′,5,7-tetramethoxyflavan-3-yloxy)flavan-3,4-diols (24) and (25). The reaction between the 2-acetoxy-3-bromoflavans (4) and (5) and 2,4-cis-flavan-4-ols (2) and (3) yields 2,3-cis-3-bromo-2-(2,4-cis-flavan-4-yloxy)flavans (6)–(11) which similarly are convertible into biflavonoid 3,4-cis-diols [e.g.(12) and (13)]. Flavan-3,4-trans-diols [e.g.(30)] react with 2-acetoxy-3-bromoflavans [e.g.(4)] to give 2,3-cis-3-bromo-2-(2,3-trans-3,4-trans-4-hydroxyflavan-3-yloxy)-(31) and (33) and 2,3-cis-3-bromo-2-(2,3-trans-3,4-trans-3-hydroxyflavan-4-yloxy)flavans (35) and (37), and flavan-3,4-cis-diols [e.g.(42)] give the corresponding 2,3-cis-(2,3-trans-3,4-cis)-compounds (43)–(46). The structures and stereochemistries of the biflavonoids have been established by analysis of n.m.r. spectra and by chemical transformations.