Stereoselective total synthesis of the E-isomer of putative lucentamycin A

A synthesis of the E-isomer of the proposed structure of the novel tripeptide, lucentamycin A. was performed in an attempt to define the correct stereochemistry of this natural product. The synthetic route developed employs a stereoselective Rh-catalyzed reductive cyclization process to generate the key pyrrolidine residue in the target and a stereospecific inversion of the Z-olefin geometry to form desired E-isomer. Subsequent amide coupling reactions afforded the desired E-isomer of putative lucentamycin A. A comparison of the NMR data of synthetic E-la with that of the naturally occurring lucentamycin A demonstrated that they are not identical substances and the E-la was found to display no anti-proliferative activity on the colon cancer cell line HCT-116 in contrast to natural lucentamycin A. (C) 2012 Elsevier Ltd. All rights reserved.