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.
Mycobacterium tuberculosis, 1, sulfoglycolipids, 1'-Glycosylation, asymmetric trehaloses, deoxypropionates, oxazolidinones
NCBI PubMed ID: 36349422Publication DOI: 10.1002/anie.202212514Journal NLM ID: 0370543Publisher: Weinheim: Wiley-VCH
Correspondence: K.K.T. Mong
; C.H. Lin
Institutions: Applied Chemistry Department, National Yang Ming Chiao Tung University (Previously National Chiao Tung University), 1001, University Road, Hsinchu City, Taiwan, R. O. C., Institute of Biological Chemistry, Academia Sinica, No.128, Academia Road Section2, Nan-Kang, Taipei, 11529, Taiwan
Methods: 13C NMR, 1H NMR, TLC, chemical synthesis, HPLC, glycosylation, optical rotation measurement, HR-ESI-MS
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