Formal total synthesis of grahamimycin A1

(S)-t-Butyldimethylsiloxy-2-hexenoic acid and its (R)-isomer were prepared from (S)- and (R)-3-hydroxybutanoic acid esters, respectively. Condensation of the both isomers with 2-(p-toluenesulfonyl)ethyl (4S,5S,7R)-7-hydroxy04,5-dimethylmethylenedioxyoctanoate, synthesized frommethyl 4,6-dideoxy-α-D-xylo-hexopyranoside, gave the corresponding esters which were converted into precursors of seco acids of grahamimycin A1 with S or R configuration at the C-6 position (grahamimycin A1 numbering). The (6S)- and (6R)-isomers were respectively subjected to macrolactonization by the use of diethyl azodicarboxylate-triphenylphosphine system or Yamaguchi procedure to afford 11,12-dihydroxy-grahamimycin A1 whose oxidation to grahamimycin A1 has already been reported.