Efficient synthesis of methyl lycotetraoside, the tetrasaccharide constituent of the tomato defence glycoalkaloid α-tomatine

Abstract

Branched oligosaccharide lycotetraose, beta-D-glucopyranosyl-(1-->2)-[beta-D-xylopyranosyl-(1-->3)]-beta-D-glucopyranosyl-(1-->4)-beta-D-galactopyranose, is a key constituent of many steroidal saponins, including glycoalkaloid alpha-tomatine, which is involved in protection of plants from invading pathogens. A new synthesis of the methyl beta-lycotetraoside () is described. Key steps of the synthesis include two successive glycosylation reactions of disaccharide acceptor methyl (4,6-O-benzylidene-3-O-p-methoxybenzyl-beta-D-glucopyranosyl)-(1-->4)-2,3,6-tri-O-benzyl-beta-D-galactopyranoside with readily available benzoylated trichloroacetimidates of alpha-D-glucopyranose and alpha,beta-D-xylopyranose. This scheme allows sequential glycosylation in one-pot on account of the convenient in situ removal of a p-methoxybenzyl protecting group under the acid conditions of the first glycosylation step. Following deprotection, tetrasaccharide was obtained in 19% yield over eight steps.

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

“…The order of glycosylations was of paramount importance in the synthesis of methyl lycoteraoside, a tetrasaccharide constituent of α-tomatine, where steric hindrance was the culprit in the unsuccessful pathway but could be circumvented by an alternative scheme, both of which employed a monsaccharide as the donor and a trisaccharide as an acceptor. 22 Herein, the pertinently functionalized monosaccharide building blocks facilitated glycosylation to give a disaccharide donor that subsequently was super-armed by substitution with several TBS-groups enforcing sterical crowding and conformational changes of the constituent sugar residues. The successful glycosylation, with very high β-selectivity, of the hydroxyl group at a secondary carbon utilized a disaccharide acceptor molecule that facilitated formation of a tetrasaccharide, which after protection gave the branched target molecule.…”

Bioactivities of Glycoalkaloids and Their Aglycones from Solanum Species

“…For example, to examine the activity of the tomatidine aglycone 25 , it would be interesting to attach the chacotriose sugar 12 and compare the results with those documented in the literature. Although the lycotetraose 14 and chacotriose 12 sugars have been synthesized, − they have not been attached to alternate aglycones and tested for bioactivity, which would help further elucidate the importance of the carbohydrate attachments.…”

Interaction of the Glycoalkaloid Tomatine with DMPC and Sterol Monolayers Studied by Surface Pressure Measurements and Brewster Angle Microscopy

“…It is hoped that these studies will ultimately provide insight into possible further application of these compounds in drug delivery and immunological formulations. The saponins and glycoalkaloids have recently begun to attract the attention of synthetic carbohydrate chemists, and the unique interactions between the oligosaccharide portions of these molecules may soon be able to be exploited in synthetic bioconjugates. , …”

“…The saponins and glycoalkaloids have recently begun to attract the attention of synthetic carbohydrate chemists, and the unique interactions between the oligosaccharide portions of these molecules may soon be able to be exploited in synthetic bioconjugates. 50,51…”