Chemical synthesis of NodRm-1: the nodulation factor involved in Rhizobium meliloti-legume symbiosis
Abstract
A total synthesis of the sulfated lipotetrasaccharide (NodRm-1) is described. First, the disaccharide glycosyl donor—O-(2-azido-3,4,6-tri-O-benzyl-2-deoxy-β-D-glucopyranosyl)-(1 →4)-3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranosyl chloride 3a or the corresponding trichloroacetimidate 3b— and the disaccharide glycosyl acceptor — benzyl O-(3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranosyl)-(1 →4)-3-O-benzyl-2-deoxy-2-phthalimido-6-O-pivaloyl-β-D-glucopyranoside 4 have been synthesized from monosaccharide moieties through a series of well established reactions. Then the crucial coupling between compound 4 and chloride 3a or imidate 3b gave the corresponding β-linked tetrasaccharide 2. Transformation of the protecting group and subsequent 6-O-sulfation converted tetrasaccharide 2 into the sulfated, N-acetylated compound 25. Finally, hydrogenolysis of compound 25, followed by selective N-acylation with 3-acylthiazolidine-2-thione 29, afforded NodRm-1 as its sodium salt.