Synthesis of the tetrasaccharide glycoside moiety of Solaradixine and rapid NMR-based structure verification using the program CASPER

Abstract

The major glycoalkaloid in the roots of Solanum laciniatum is Solaradixine having the branched tetrasaccharide β-d-Glcp-(1→2)-β-d-Glcp-(1→3)[α-l-Rhap-(1→2)]-β-d-Galp linked to O3 of the steroidal alkaloid Solasodine. We herein describe the synthesis of the methyl glycoside of the tetrasaccharide using a super-armed disaccharide as a donor molecule. A 2-(naphthyl)methyl protecting group was used in the synthesis of the donor since it was tolerant to a wide range of reaction conditions. The 6-O-benzylated-hexa-O-tert-butyldimethylsilyl-protected β-d-Glcp-(1→2)-β-d-Glcp-SEt donor, which avoided 1,6-anydro formation, was successfully glycosylated at O3 of a galactoside acceptor molecule. However, subsequent glycosylation at O2 by a rhamnosyl donor was unsuccessful and instead a suitably protected α-l-Rhap-(1→2)-β-d-Galp-OMe disaccharide was used as the acceptor molecule together with a super-armed β-d-Glcp-(1→2)-β-d-Glcp-SEt donor in the glycosylation reaction, to give a tetrasaccharide in a yield of 55%, which after deprotection resulted in the target molecule, the structure of which was verified by the NMR chemical shift prediction program CASPER.