Abstract
Glycosphingolipids (GSL) present on cell surface are believed to play imortant physiological roles for cell surface molecular recognition mechanisms. In order to supply enough amount of chemically well characterized GSL for biochemical as well as biophysical studies, it is prerequisite to develop synthetic routes to such molecules with high stereo- and regio-control. From such view points, our projects on synthetic studies on GSL has started several years ago. As part of these projects, we describe here for the first time total synthesis of globo-series glycopentaosyl GSL 1 and 2, so-called SSEA-31,2 and Para-Forsmann3 antigen, respectively. Retrosynthetic analysis of 1 and 2 is depicted in scheme 1. A) Synthesis of SSEA-3 (1) Boron trifluoride etherate promoted glycosylation of glycotriosyl acceptor 5 with trichloroacetimidate 6 gave a 22% yield of the desired glycopentaoside 7 which was futher converted into a glycosyl donor 11 in 4 steps. Crucial coupling between 11 and 3 did afford 12 in 33% yield which was deprotected to give 1. Synthetic 1 was completely identified with natural 1 through comparison of their ^1H-nmr data. B) Synthesis of Para-Frossman antigen 2 Glycosylation of alcohol 15 with bromide 14 gave a 94% yield of 16 which was converted into 18 in 39% overall yield in 4 steps. Compound 18 was converted into a glycosyl donor 23 which was coupled with 5 to give as high as a 58% yield of the desired 29 in the presence of (Bu_4N)_2CuBr_4-AgOTf in CH_3NO_2 at 0°. Conversion of 29 into a glycosyl donor 35 was successfully achieved and crucial coupling with a glycosyl acceptor 4 gave about 50% yield of the desired 37 which was further transformed into a target 2 in a conventional manner. In summary, first total syntheses of both 1 and 2 were achieved by use of a common glycotriosyl acceptor 5.
