Syntheses and Preliminary Biological Evaluations of the Dibromopyrrole-Containing Marine Natural Products Agesasine A,Agesasine B,Longamide E and Various Congeners

Total syntheses of the title marine natural products have been achieved and so confirming the structures originally assigned to them. Upon subjecting agesasine A and its corresponding ethyl ester to Mitsunobu conditions, a 1,5-cyclodehydration reaction takes place to give 2-oxazolines. In contrast, on subjecting agesasine B to the same Mitsunobu conditions, a simple dehydration reaction occurs to give the corresponding acrylate. A total synthesis of longamide E was achieved by engaging a 1,2-disubstituted pyrrole in a lactam-forming reaction and this was followed by a two-fold and fully regio-controlled bromination reaction. A distinctly different and possibly biomimetic route was used to synthesize, via the open-chain natural product nakamurine B, longamide B and its methyl ester. Preliminary biological evaluations of the title alkaloids and various analogues against a small human cancer cell line panel reveals cytotoxic properties that vary significantly with structure.