Chemical Synthesis of Rare, Deoxy-Amino Sugars Containing Bacterial Glycoconjugates as Potential Vaccine Candidates

Abstract

Bacteria often contain rare deoxy amino sugars which are absent in the host cells. This structural difference can be harnessed for the development of vaccines. Over the last fifteen years, remarkable progress has been made toward the development of novel and efficient protocols for obtaining the rare sugar building blocks and their stereoselective assembly to construct conjugation ready bacterial glycans. In this review, we discuss the total synthesis of a variety of rare sugar containing bacterial glycoconjugates which are potential vaccine candidates.

Keywords: bacterial glycoconjugates; rare deoxy-amino sugars; stereoselective glycosylation; total synthesis; vaccine candidates; zwitterionic polysaccharides.

Figure 1

Representative examples of rare deoxy amino monosaccharides present in bacteria.

Scheme 1

Ito’s first-generation synthesis of the heptasaccharide from C. jejuni.

Scheme 2

Glycosylation of C. jejuni hexasaccharide with bacillosamine.

Scheme 3

Ito’s second-generation total synthesis of C. jejuni heptasaccharide.

Scheme 4

Van der Marel’s assembly of protected tetrasaccharide repeating unit of zwitterionic polysaccharides (ZPS) A1.

Scheme 5

First total synthesis of ZPS A1 by Seeberger and co-workers.

Scheme 6

Kulkarni’s synthesis of the rare disaccharide donor unit of ZPS A1.

Figure 2

Structure of ZPS A1 with alternating charges on adjacent monosaccharides.

Scheme 7

Bundle’s first total synthesis of Streptococcus pneumoniae ZPS trisaccharide.

Scheme 8

Bundle’s total synthesis of Streptococcus pneumoniae ZPS hexasaccharide.

Scheme 9

Codée’s synthesis of all the Streptococcus pneumoniae Sp1 ZPS trisaccharides.

Scheme 10

Seeberger’s total synthesis of thioether linked S. pneumoniae Sp1 trisacharide.

Scheme 11

Schmidt’s total synthesis of lipoteichoic acid of Streptococcus pneumoniae.

Figure 3

Structure of lipoteichoic acid of S.pneumoniae.

Scheme 12

Seeberger’s total synthesis of capsular polysaccharides (CPS) repeating unit of S. pneumoniae Serotype 4.

Scheme 13

Seeberger’s total synthesis of S. pneumoniae serotype 12F CPS repeating unit.

Scheme 14

Seeberger’s synthesis of S. pneumoniae serotype 5 glycan.

Scheme 15

Mulard’s total synthesis of ZPS of Shigella sonnei.

Scheme 16

Kulkarni’s one-pot synthesis of ZPS of P. alcalifaciens O22.

Scheme 17

Adamo’s first total synthesis of Staphylococcus aureus type 5 repeating unit.

Scheme 18

Boons’ total synthesis of Staphylococcus aureus type 5 repeating unit.

Scheme 19

Demchenko’s total synthesis of Staphylococcus aureus type 5 repeating unit.

Scheme 20

Codée’s total synthesis of Staphylococcus aureus type 5 repeating unit.

Scheme 21

Demchenko’s total synthesis of Staphylococcus aureus type 8 repeating unit.

Scheme 22

Codée’s total synthesis of Staphylococcus aureus Strain M repeating unit.

Scheme 23

Kulkarni’s total synthesis of DATDG containing pilin glycan of N. meningitidis.

Scheme 24

Kulkarni’s total synthesis of Bac containing pilin glycan of N. meningitidis.

Scheme 25

Kulkarni’s first total synthesis of Bacillus cereus Ch HF-PS.

Scheme 26

Kulkarni’s total synthesis of glycan of Yersinia enterocolitica.

Scheme 27

Kulkarni’s synthesis of P. chlororaphis subsp. aureofaciens strain M71 glycan.

Scheme 28

Synthesis of P. shigelloides serotype 51 aminoglycoside trisaccharide antigen.

Scheme 29

Li’s synthesis of Pseudomonas aeruginosa 1244 Pilin glycan.