Synthesis of mycothiol, 1D-1-O-(2-[N-acetyl-L-cysteinyl]amino-2-deoxy-alpha-D-glucopyranosyl)-myo-inositol, principal low molecular mass thiol in the actinomycetes.
Members of the actinomycetes produce 1D-1-O-(2-[N-acetyl-L-cysteinyl]amino-2-deoxy-alpha-D-glucopyranosyl)-myo-inositol or mycothiol 1 as principal low molecular mass thiol. Chemical synthesis of a biosynthetic precursor of mycothiol, the pseudodisaccharide 1D-1-O-(2-amino-2-deoxy-alpha-D-glucopyranosyl)-myo-inositol 13 was achieved by the following steps: (1) Enantioselective synthesis gave the glycosyl acceptors (-)-2,3,4,5,6-penta-O-acetyl-D-myo-inositol D-7 and the corresponding L-isomer L-7. (2) Condensation of D-7 and L-7 with the glycosyl donor 3,4,6-tri-O-acetyl-2-deoxy-2-(2,4-dinitrophenylamino)-alpha-D-glucopyranosylbromide afforded the corresponding alpha and beta anomeric products, which could be resolved by silica gel chromatography. (3) Deprotection of these by hydrolysis using an anion exchange resin gave 1D- and 1L-1-O-(2-amino-2-deoxy-alpha-D-glucopyranosyl)-myo-inositol 13 and 15 and the corresponding beta-coupled anomers 14 and 16. Only 13, and to a much lesser extent 15, were used by enzymes present in an ammonium sulphate fraction of a cellfree extract of Mycobacterium smegmatis for the enzymatic synthesis of mycothiol. In the absence of acetyl-SCoA, the immediate biosynthetic precursor of 1, desacetylmycothiol, was the major product.
Jardine
M Anwar
MA
Department of Chemical Pathology, University of Cape Town Medical School, Observatory 7925, South Africa.
Spies
Hendrik S C
HS
Nkambule
Comfort M
CM
Gammon
David W
DW
Steenkamp
Daniel J
DJ
D000192:Actinomycetales / Q000737:chemistry*; D003545:Cysteine; D004187:Disaccharides / Q000096:biosynthesis* / Q000138:chemical synthesis / Q000378:metabolism; D006020:Glycopeptides; D007294:Inositol; D008970:Molecular Weight; D020102:Mycobacterium smegmatis / Q000201:enzymology; D019906:Nuclear Magnetic Resonance, Biomolecular; D011720:Pyrazoles / Q000138:chemical synthesis / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000378:metabolism
D004187:Disaccharides; D006020:Glycopeptides; D011720:Pyrazoles; D013438:Sulfhydryl Compounds; C089265:mycothiol; D007294:Inositol; D003545:Cysteine