Programmable reactivity-based one-pot oligosaccharide synthesis.
A detailed protocol is described for the application of a programmable one-pot oligosaccharide synthesis methodology to the synthesis of fucosyl GM1. This serves as a general example of the application of this method to the synthesis of any desired oligosaccharide. The method relies on a large database of relative reactivities for differentially protected tolyl thioglycoside donor molecules and a computer program to suggest the best order of addition for assembly of the oligosaccharide in optimal yield and with the fewest operations. The product is a protected form of the desired oligosaccharide isolated in 47% yield, which is then deprotected using standard procedures to provide fucosyl GM1 oligosaccharide (1) in 44% yield. The total time for synthesis of 1 from building blocks 3, 4 and 5 is approximately 4 d, whereas synthesis of the same compound by traditional stepwise procedures would take significantly longer. Protocols for the synthesis of thioglycoside building blocks 3 and 4 are also described.
Lee
Jinq-Chyi
JC
Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Greenberg
William A
WA
Wong
Chi-Huey
CH
D005677:G(M1) Ganglioside / Q000031:analogs & derivatives / Q000138:chemical synthesis; D009844:Oligosaccharides / Q000138:chemical synthesis*; D012984:Software
D009844:Oligosaccharides; D005677:G(M1) Ganglioside; C039123:fucosyl GM1 ganglioside