Synthesis of trehalose monomycolate (TMM) analogs for probing the specificity of macrophage-inducible C-type lectin (Mincle)

• Main Author: Sangalang, Reymart V.
• Format: text
• Language: English
• Published: Animo Repository 2016
• Online Access: https://animorepository.dlsu.edu.ph/etd_masteral/5159
• Institution: De La Salle University

The macrophage-inducible C-type lectin (Mincle) is a protein involved in the recognition of trehalose monomycolate (TMM) and trehalose dimycolate (TDM), glycolipids produced by mycobacteria, including the human pathogen Mycobacterium tuberculosis. This project aimed to establish a chemical synthesis of TMM analogs that will be used to probe the molecular details of this carbohydrate protein interactions. The three (3) TMM analogs were synthesized using the designed general synthetic procedure for trehalose monoesters with 2,3- antistereochemistry. Incorporation of the desired functional groups to form mycolates was achieved by enolate alkylation, followed by Noyoris asymmetric reduction of b,b- ketoesters then antiselective alkylation according to Frater to give b,b- hydroxy alcohols as the key steps. Regioselective debenzylation of trehalose unit using DIBAL-H was used to improve monoester formation. Thus, we prepared analogs 41A, 41B and 41C in moderate to high yields. In addition to serving as useful biochemical tools, these molecules may have potential as novel adjuvants