Synthesis of macrocyclic polyhydroxy tetralactams derived from L-tartaric acid and beta-hydroxyglutaric acid

The synthesis of new 16-, 18-, 19- or 20-membered secondary tetralactams with L-tartaric acid or beta-hydroxyglutaric acid moieties is investigated. The stepwise synthesis with an intermediate diamide diamine provides overall good yields (30-55%) compared with other processes using an intermediate diamide diacid or direct macrocyclization. This synthetic pathway leads to symmetrical or unsymmetrical polyhydroxytetralactams with variable hydroxyl group number. Use of mild acylating agents in this approach allows to avoid the protection-deprotection steps of hydroxyl groups. (C) 1997 Elsevier Science.