ABSOLUTE STEREOCHEMISTRY OF SOULATTROLIDE AND ITS ANALOGS

The absolute stereochemistry of a group of dipyranocoumarins, some of which are potent inhibitors of HIV-1 reverse transcriptase, was examin ed. Soulattrolide {2H,6H,10N-benzo[1,2-b:3,4-b':5,6-b<double prime>]tr ipyran-2-one, 11,12-dihydro-12-hydroxy-6,6,10,11-tetra [10S-(10 alpha, 11 beta,12 beta)]-; CAS Registry No. 65025-62-9} and cordatolide B, tw o of these dipyranocoumarins, were converted to alpha-methoxy-alpha-(t rifluoromethyl)phenylacetate (MTPA) derivatives and investigated by H- 1 NMR spectroscopy. A correlation of H-1 NMR chemical shift difference s with those predicted by Mosher's concept alone was inadequate to ass ign confidently the absolute stereochemistries, due to the fact that i n both of these molecules too few protons are present on one side of t he MTPA plane. However, energetically favored conformations obtained b y molecular mechanics calculations provided satisfactory rationalizati ons for the observed anisotropic shifts in H-1 NMR data. The combined results of the two techniques allow us to assign the absolute configur ation of both soulattrolide and cordatolide B as (10S,11R,12S). The ab solute configurations of the other structurally related inhibitors, in cluding inophyllums B, D, and P, costatolide, calanolides A, B, and C, and cordatolide A, are also assigned on the basis of chemical convers ions and correlations of their chiroptical properties. Subtleties in t he application of the Cahn-Ingold-Prelog rules to the designation of R or S configurations at some positions in these compounds make basical ly trivial errors particularly easy.