Synthetic avenues towards a tetrasaccharide related to Streptococcus pneumonia of serotype 6A.

Aritra Chaudhury,Rina Ghosh,Mana Mohan Mukherjee

doi:10.3762/bjoc.14.95

Abstract

Streptococcus pneumonia (SPn) is a Gram-positive bacterium which causes life threatening diseases. The bacteria protect themselves against non-specific host defence by an external polysaccharide (PS) capsule which bears a repeating unit, α-D-Galp(1->3)-α-D-Glcp(1->3)-α-L-Rhap(1->3)-D-Rib (SPn 6A). A closer look at the structure reveals the presence of α-linked galactose and glucose residues. The synthesis of these 1,2-cis glycosidic linkages are considered challenging particularly in the context of a one-pot oligosaccharide synthesis. We have synthesized the aforesaid tetrasaccharide (SPn 6A) based on both stepwise and sequential one-pot glycosylation reactions using easily accessible common building blocks; eventually similar overall yields were obtained in both cases.

Highlights

Complex glycans serve as attractive targets for carbohydratebased vaccines and therapeutics [1,2,3]
Streptococcus pneumonia (SPn) has been posing a serious threat in recent times. It is a major cause of pneumonia, bacteraemia, and meningitis in immune-compromised patients, elderly and children
A UNICEF/WHO survey has estimated that 920136 children died of pneumonia in 2015 accounting for 16% of all fatalities under the age of five [4]

Summary

Introduction

Complex glycans serve as attractive targets for carbohydratebased vaccines and therapeutics [1,2,3]. We wish to report synthetic routes to the SPn 6A tetrasaccharide via stepwise as well as one-pot sequential glycosylation strategies. Keeping in mind our objective to synthesize the SPn 6A tetrasaccharide following stepwise as well as one-pot synthetic strategies based on common building blocks, a retrosynthetic analysis was made which led us to galactose-based donor 2 [26], ribitol-based acceptor 7 [22] and a gluco-rhamno-based disaccharide (3a/3b) to contemplate the synthesis of the tetrasaccharide derivative 1 (Figure 2).

Results

Conclusion