Synthesis and Stereochemistry of Indolactam-V, An Active Fragment of Teleocidins. Structural Requirements for Tumor-Promoting Activity.

Article abstract of DOI:10.1016/S0040-4020(01)96073-9

(-)-Indolactam-V, which is an active fragment of the potent tumor promoters teleocidins and has also been isolated as a Streptoverticillium metabolite, has been synthesized starting from 4-nitrogramine.The absolute stereochemistry of (-)-indolactam-V has been determined to be (9S, 12S), which suggests that teleocidins and related compounds are biosinthesyzed from L-amino acids.Three unnatural diastereoisomers were also synthesized.The NMR spectra of (-)- and (+/-)-indolactam-V and its derivatives showed that they exist in two conformational states in solution.The structures of the two conformers were deduced from the chemical shifts, coupling constants and nuclear Overhauser effects to be SOFA and TWIST from which are characterized by trans and cis amide bonds, respectively.The calculated ratio of the two conformers was consistent with the observed ratio.