Chemical synthesis of pentasaccharide of capsular polysaccharide from Acinetobacter baumannii for immunological evaluation
Date Issued
2015
Date
2015
Author(s)
Fu, Chun
Abstract
Acinetobacter baumannii are an aerobic gram-negative bacillus and an opportunistic bacterial pathogen primarily associated with hospital-acquired infections. It has low virulence but is capable of causing infection in organ transplants and people with compromised immune systems and it can cause serious and life-threatening infections. During recent years, it has become an increasing danger to the global healthcare system as a result of its rapid proliferation and increasing resistance to antibiotics and disinfectants. There are some successful cases of preventing of bacterial infection, like Streptococcus pneumonia and Neisseria meningitides. Recent reports show that the capsular polysaccharide is a virulence factors. Their analytic results show that one of structures of A. baumannii ATCC 17978 CPS is composed by the pentasaccharide as repeating unit (show as below). From the chemical structure point of view, it is not only unique, but also no synthetic method has been reported. In this work, we would like to design a general and flexible synthetic method to prepare this pentasaccharide and its analogues including new fragments or intermediates. Most importantly, we focused on the synthesis of structurally unique and external monosaccharide A, using glucosamine as a starting material. Besides, the key transformations for preparing the A ring are : (1) the hydroxy group was converted to the acetamido group at the equatorially C3 position, and (2) the acetyl group at the C4 position and the carboxylic acid group at the C5 position were established. Expectedly, this approach toward the preparation of the monosaccharide A might be applied to the synthesis of the pentasaccharide and its derivatives or fragments, which allows us for further biological evaluation and immune response study in the future.
Subjects
Acinetobacter baumannii
capsular polysaccharide
chemical synthesis
glycosylation
saccharide building blocks
Type
thesis