%0 Journal Article
%@ 0002-7863
%A Ribe, S
%A Kondru, RK
%A Beratan, DN
%A Wipf, P
%D 2000
%F pittir:25622
%J Journal of the American Chemical Society
%N 19
%P 4608 - 4617
%T Optical rotation computation, total synthesis, and stereochemistry assignment of the marine natural product pitiamide A
%U http://d-scholarship-dev.library.pitt.edu/25622/
%V 122
%X 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.