Synthesis and enzyme-catalysed reductions of 2-oxo acids with oxygen containing side-chains

A series of novel 2-oxo esters with protected alcohols at the 3-, 4-, 5-, 6 - and 7-positions has been prepared either via coupling of an aldehyde with an organometallic reagent (Zn, In or Cr) or via a one-carbon homologation of the precursor acid. A one-pot dual enzyme system was used to convert the simpler 2-oxo acids (with a single MOM ether at either C-3 or C-4) into en antiopure protected 2,3- and 2,4-dihydroxy acids in good yields, but in the cases of the more complex trisubstituted substrates, significant decomposi tion occurred. Biotransformations have proved valuable for the enantioselec tive synthesis of protected 2,6,7-trihydroxyhept-3-enoic acids.