Tunable Strategy for the Asymmetric Synthesis of Sulfoglycolipids from <i>Mycobacterium tuberculosis</i> To Elucidate the Structure and Immunomodulatory Property Relationships

Abstract We developed a versatile asymmetric strategy to synthesize different classes of sulfoglycolipids (SGLs) from Mycobacterium tuberculosis . The strategy features the use of asymmetrically protected trehaloses, which were acquired from the glycosylation of TMS α ‐glucosyl acceptors with benzylidene‐protected thioglucosyl donors. The positions of the protecting groups at the donors and acceptors can be fine‐tuned to obtain different protecting‐group patterns, which is crucial for regioselective acylation and sulfation. In addition, a chemoenzymatic strategy was established to prepare the polymethylated fatty acid building blocks. The strategy employs inexpensive lipase as a desymmetrization agent in the preparation of the starting substrate and readily available chiral oxazolidinone as a chirality‐controlling agent in the construction of the polymethylated fatty acids. A subsequent investigation on the immunomodulatory properties of each class of SGLs showed how the structures of SGLs impact the host innate immunity response.