Recently, various types of important biological functions of gangliosides in biological systems have been reported by many groups2-*. Consequently, a facile, regio-and a-stereo-selective glycoside synthesis of sialic acid is critically important for the synthesis of a variety of gangliosides and their analogs, in order to investigate the structure-function relationship of sialoglycoconjugates at the molecular level. Previously, we demonstrated6 a new, efficient cr-glycosylation of sialic acid by use of dimethyl(methylthio)sulfonium triflate (DMTST)' as the glycosyl promoter, and the suitably protected glycosyl acceptors in acetonitrile under kinetically controlled conditions, and accomplished8 a regio-and stereo-selective synthesis of gangliosides GM,, GM,, and their analogs.
In this communication, an application of the method to the first total synthesis of sialyl lactotetraosyl ceramide9 (IV3 NeuAcLc,Cer), which has been detected as a ganglioside antigen in human lung carcinoma by a monoclonal antibody in 1985, and found to be widespread as a minor component in many different carcinomas, will be described. Dibutyltin oxide-mediated, selective etherification'O of 2-(trimethylsilyl)ethyl O-~-D-galactopyranosyl-(I~4)-~-D-glucoyranoside11 (1) to give the 3'-0-(4methoxybenzyl) derivative 2 {m.p. 184.5", [(Y]~ -3.2" (1: 1 methanol-dichloromethane)} could be achieved in 74% yield. Benzylation of 2 with benzyl bromide in N,N-dimethylformamide in the presence of sodium hydride gave 3 (79%), which was treated with 2,3-dichloro-5,6-dicyanobenzoquinonel* in dichloromethanewater for 1 h at room temperature to afford compound 4 {[aID +0.2" (dichloromethane)} in 85% yield. The glycosylation of 4 with 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-D-glucopyranosyl bromide13 (5) in the presence of silver carbonate, silver perchlorate, and molecular sieves 4A (MS4A) in dichloromethane for 16 h at room temperature gave the desired /3-glycoside 6 {[cr]n -3.7" (chloroform)} in 86% yield; significant *Synthetic Studies on Sialoglycoconjugates, Part 11. For Part 10, see ref. 1.