Total Synthesis of the Trisaccharide Unit of the Molecular Chaperone Down-Regulator Versipelostatin

Abstract

The first synthesis of the trisaccharide unit of versipelostatin, a down regulator of grp78, was achieved, utilizing methyl­ triflate promoted glycosidations of thioethyl glycosyl donors of d-digitoxose and d-cymarose with protected digitoxal. The synthesis was terminated by the preparation of a thioglycoside based on diethyldithionophosphonic acid which is ready for further glycosidations with aglycons. Comparison of NMR spectroscopic data of two trisaccharides with the data reported for versipelostatin supported the configuration of the monosaccharide units as well as glycosidic linkages.

Key words

antibiotics - deoxy sugars - glycols - glycosidations - glycoconjugates - thioglycosides

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7

An alternative glycosidation sequence which was initiated from the eastern part using benzyl digitoxides turned out to be unsuccessful due to selectivity problems. In addition, the activation of 2-iodo-oleandrosyl acetates led to complex product mixtures, whereas a disarmed-armed glycal approach using NIS also failed due to the low reactivity of
4-O-tert-butyldimethylsilyl-d-oleandral.