CHEMOENZYMATIC ENANTIOCONTROLLED SYNTHESIS OF (-)-SPECIONIN

Specionin acetate la has been synthesized from chlorobenzene in 15 steps and compared with an authentic sample. The chirality was incorporated into the synthesis by microbial dioxygenation of chlorobenzene using a mutant strain of Pseudomonas putida, 39D, to produce 1-chloro-2,3-dihydroxycyclohexa-4,6-diene, which was elaborated into enone 5. Addition of the lithium dienolate derived from ethyl 4-(dimethyl-tert-butylsiloxy)-2-bromocrotonate to this enone provided vinylcyclopropanes 7, which underwent a low-temperature vinylcyclo-propane-cyclopentene rearrangement to tricyclic ketones 8 upon treatment with either trimethylsilyl iodide or tetrabutylammonium fluoride at -78-degrees-C. Following the deoxygenation of the carbonyl and the convergent transformation of both C-4 isomers to a single allylic acetate 11 via either esterification or Mitsunobu inversion, the epoxidation and generation of the bisacetal was accomplished according to the known protocol. The overall yield of this synthesis was 9% for the sequence 5 to 11. Spectral data and experimental details are provided for key compounds.