Synthesis of mycothiol, 1D-1-O-(2-[N-acetyl-l-cysteinyl]amino-2-deoxy-α-d-glucopyranosyl)-myo-inositol, principal low molecular mass thiol in the actinomycetes Original Research Article

Members of the actinomycetes produce 1D-1-O-(2-[N-acetyl-l-cysteinyl]amino-2-deoxy-α-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-α-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)-α-d-glucopyranosylbromide afforded the corresponding α and β 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-α-d-glucopyranosyl)-myo-inositol 13 and 15 and the corresponding β-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, t