275804-99-4Relevant academic research and scientific papers
Optical rotation computation, total synthesis, and stereochemistry assignment of the marine natural product Pitiamide A
Ribe, Seth,Kondru, Rama K.,Beratan, David N.,Wipf, Peter
, p. 4608 - 4617 (2007/10/03)
We report the joint application of ab initio computations and total synthesis to assign the absolute configuration of a new natural product. The expected specific rotations of the (7S,10R)- and (7R,10R)-isomers of pitiamide A in a CHCl3 solvent continuum model were determined as +8 and -39, respectively, by CADPAC calculations of the electric-dipole-magnetic-dipole polarizability tensor. Total syntheses of these two stereoisomers of the marine metabolite were achieved by a convergent strategy that utilized Evans' oxazolidinone alkylation, a novel water-accelerated modification of Negishi's zirconocene-catalyzed asymmetric carbometalation as well as an unusual segment condensation via Mitsunobu alkylation of a nosyl-activated amide. The experimental optical rotation measurements confirmed the results of the computational optical rotation predictions. On the basis of NMR comparisons, the configuration of pitiamide A was assigned as (7R,10R). These studies highlight the considerable structural significance of [α]D data, but, because the optical rotation of the natural product was different from either synthetic diastereomer, our work serves also as an illustration of potential problems with obtaining accurate experimental [α]D data for natural samples.
