Chemoenzymatic synthesis of the epimeric 6C-methyl-D-mannoses from toluene

The title compounds 1 and 2, which are effective and specific inhibitors of phosphohexomutases, have been prepared in enantiomerically pure form from toluene. The initial step of the reaction sequence involves enzymatic cis-1,2-dihydroxylation of toluene by E. coli JM109 (pDTG601) to give the cis-1,2-dihydrocatechol 3. The latter compound is then converted, via a series of chemical oxidation and reduction steps, into compounds 1 and 2. The X-ray crystal structures of the bis-acetonide derivatives 11, 13 and 14 have been determined.