First total synthesis of pro-resolving and tissue-regenerative resolvin sulfido-conjugates

Abstract

The first total synthesis of the pro-resolving and tissue-regenerative resolvin sulfido-conjugates: 7S,8R,17S-RCTR1, 7S,8R,17S-RCTR2 and 7S,8R,17S-RCTR3, derived from docosahexaenoic acid, has been achieved. Two synthetic approaches are described. Chiral centers 7S and 8R were introduced in both approaches via a chiral pool strategy starting from 2-deoxy-d-ribose. The 17S chiral center was introduced either by a chiral pool strategy or by an enzymatic hydroxylation with lipoxidase. Wittig reactions, selective epoxide formation and epoxide opening with glutathione, l-cysteinylglycine and l-cysteine respectively, were the key steps in the synthesis.