Synthesis of epecatechin-4α, 8-epicatechin dimers and derivatives thereof
AssigneeMars, Incorporated
InventorsAlan P. Kozikowski, Leo J. Romanczyk Jr., Werner Tückmantel
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Abstract
Oligomeric procyanidins containing 4α-linked epicatechin units are rare in nature and have hitherto not been accessible through stereoselective synthesis. Provided herein is the preparation of the prototypical dimer, epicatechin-4α,8-epicatechin, by reaction of the protected 4-ketones with aryllithium reagents derived by halogen/metal exchange from the aryl bromides. Removal of the 4-hydroxyl group from the resulting tertiary benzylic alcohols is effected by tri-n-butyltin hydride and trifluoroacetic acid in a completely stereoselective manner, resulting in hydride delivery exclusively from the β face.
Claims18
A protected dimer selected from the group consisting of 5,7,3′,4′-tetra-O-benzyl-3-O-(tert-butyldimethylsilyl)epicatechin-4α,8-[5,7,3′,4′-tetra-O-benzyl-3-O(tert-butyldimethylsilyl) epicatechin];
- 3,5,7,3′,4′-penta-O-benzylepicatechin-4α,8-(3,5,7,3′,4′-penta-O-benzylepicatechin);
- and 5,7,3′,4′-tetra-O-benzylepicatechin-4α,8-(5,7,3′,4′-tetra-O-benzylepicatechin).
A protected epicatechin-4α,8-epicatechin dimer having a 4-hydroxy group, which dimer is selected from the group consisting of 5,7,3′,4′-tetra-O-benzyl-3-O-(tert-butyldimethylsilyl)- 4-hydroxyepicatechin-4α,8-[5,7,3′,4′-tetra-O-benzyl-3-O-(tert-butyldimethylsilyl)epicatechin]and 3,5,7,3′,4′-penta-O-benzyl-4 hydroxyepicatechin-4,8-(penta-O-benzylepicatechin).
A derivatized 5,7,3′,4′-tetra-O-benzylepicatechin-4α,8-[5,7,3′,4′-tetra-O-benzyl-epicatechin] dimer having at least one 3-O-acyl group.
An epicatechin-4α,8-epicatechin dimer.
A derivatized epicatechin-4α,8-epicatechin dimer having acyl group(s) at the 5,7,3′, and/or 4′-positions.
A derivatized epicatechin-4α,8-epicatechin dimer having acyl group(s) at the 3,5,7,3′ and/or 4′ positions.
Dependencies are inferred from the claim text.