Stereospecific Synthesis of a Ribosyl-diazepanone Derivatives; a Synthetic Approach for Elucidation of the Stereochemistry of a Lipid Nucleoside Antibiotic Liposidomycin B

A new type of ribosyl-diazepanone derivative (23), the core ribosyl 7-membered heterocycle of the nucleoside antibiotic liposidomycin B has been synthesized using a chiral synthetic route that could offer accessibility to any of possible stereoisomers of 23.Starting from readily available cis-1,4-butenediol and P-D-ribose, epoxides (4) and ( 14) were obtained.Regioselective nucleophillic ring opening of these epoxides subsequently to the several reaction steps afforded key intermediates amine (9) and azido acid (19) which were ultimately coupled to furnish amide (20).During hydrogenolysis of azido aldehyde (22) an intramolecular Schiff base formation occurred yielding the desired product (23).Recently, we reported the isolation and structure determination of the nucleoside antibiotic liposidomycin B (I; Figure I), a bacterial peptidoglycan synthesis inhibitor.3.4This novel lipid nucleoside of unusual complexity possesses a branched fatty acid side chain attached to a substituted diazepanone ring containing three chiral centers, one of which is linked via an intervening asymmetric carbon to the nucleoside, uridine.It was found that'degradation of I by acid hydrolysis gave the diazepanone nucleoside subunit (ll).4Examination of the