Stereochemical investigation of bromoallenic acetogenin synthesis

ORGN 469

Robin B. Kinnel and Jakub Sroubek. Department of Chemistry, Hamilton College, 198 College Hill Road, Clinton, NY 13323
Bromoallene acetogenins are secondary metabolites of importance as immune response-mediating agents from the algae Laurencia. Presumably a bromoperoxidase (BPO) enzyme directs an internal cyclization reaction on alcohol precursors that gives rise to these bromoallene species. To investigate the muddy stereochemistry of this reaction we prepared a precursor by alkylating cyclopentanone-SAMP hydrazone enantioselectively with trans-pent-2-ene-4-yn-ol mesylate, hydrolyzing the hydrazone with oxalic acid and then reducing the resulting ketone to a cis-alcohol with the potassium complex K-Selectride. Non-selective cyclization with NBS afforded the diastereomeric bromoallenes in good yield. We shall describe our results and report on our current efforts at cyclization using a variety of enzyme preparations.