Total Synthesis of Trisaccharide Repeating Unit of Staphylococcus aureus Strain M

Abstract

An efficient total synthesis of a conjugation-ready trisaccharide repeating unit of Staphylococcus aureus strain M is reported here. The main challenges involved in this synthesis are the procurement of rare sugars (d-FucNAc and d-GalNAcA) and installation of consecutive 1,2-cis-glycosidic linkages between them. Stereoselective 1,2-cis glycosylation with the linker acceptor was achieved with easily accessible benzylidene protected d-galactosamine thioglycoside by employing a DMF modulated preactivation glycosylation method. The consecutive 1,2-cis linkages were installed with the help of solvent participation. The carboxylic acid functionality was introduced via postglycosylation oxidation on the disaccharide moiety. The total synthesis of trisaccharide repeating unit was accomplished with the longest linear sequence of 24 steps in 4.5% overall yield.

Block Synthesis and Step-Growth Polymerization of C-6-Sulfonatomethyl-Containing Sulfated Malto-Oligosaccharides and Their Biological Profiling

“…We hypothesized that methyl glycoside 30 [ 25 ] can function as a capping unit at the reducing end, ensuring the efficient formation of the oligomer series in the form of methyl glycoside. First, the preactivation method [ 39 , 40 ] was used, that is, thioglycoside 8 was activated with the NIS-TfOH promoter system, then, the mixture was stirred for 2 h and only then was acceptor 30 added to the reaction mixture ( Table 2 , Reaction 1). Unfortunately, the expected capping did not occur, the methyl glycoside unit 30 was not incorporated into the oligomers and only hemiacetal oligomers 40 – 44 were detected by MALDI-TOF MS ( Figure S9 ).…”

“…We hypothesized that methyl glycoside 30 [25] can function as a capping unit at the reducing end, ensuring the efficient formation of the oligomer series in the form of methyl glycoside. First, the preactivation method [39,40] was used, that is, thioglycoside 8 was activated with the NIS-TfOH promoter system, then, the mixture was stirred for 2 h and Disaccharide 31 and trisaccharide 32 were isolated from the reaction mixture with a 37% and 16% yield, respectively, and additional oligosaccharides up to octamers, both in the form of methyl glycosides and hemiacetals, were detected by MALDI-TOF MS. Using a NIS-AgOTf promoter system and a longer reaction time (Table 2, Reaction 3), but still adding the donor in two portions, the product ratio was slightly shifted to higher oligomers.…”

Total Synthesis of a Conjugation-Ready Tetrasaccharide Repeating Unit of Vibrio cholerae O:3 O-antigen Polysaccharide

“…Thioglycoside donors 5 and 7 as well as acceptors 6 and 8 can be synthesized from commercially available l -rhamnose and d -mannose, respectively. Our lab has developed expedient protocols − to access rare sugar building blocks in an efficient manner which has enabled access to several complex oligosaccharide RUs . This protocol has been exploited here to access the rare sugar building blocks (compounds 7 and 8 ).…”

Total Synthesis of Conjugation-Ready Tetrasaccharide Repeating Units of a Multidrug-Resistant Pathogen Acinetobacter baumannii Strain 34 and O5

“…The structural features of the two densely functionalized tetrasaccharide RUs of Acinetobacter baumannii strain 34 and O5 containing rare sugar units connected with consecutive 1,2- cis linkages attracted our attention. Over past several years, our laboratory has been involved in the synthesis of exclusively bacterial, rare deoxy amino sugars and their assembly into complex glycans − via an efficient and highly regioselective protocol involving one-pot S N 2 displacements of 2,4-bis-triflates derived from commercially available d - and l -sugars. , …”