Absolute Stereochemistry of Soulattrolide and Its Analogues

• Published in: Journal of organic chemistry 1998-02, Vol.63 (4), p.1233-1238
• Main Authors: Shi, Xiongwei, Attygalle, Athula B, Liwo, Adam, Hao, Ming-Hong, Meinwald, Jerrold, Dharmaratne, H. Ranjith W, Wanigasekera, W. M. Anoja P
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo9717752

The absolute stereochemistry of a group of dipyranocoumarins, some of which are potent inhibitors of HIV-1 reverse transcriptase, was examined. Soulattrolide {2H,6H,10H-benzo[1,2-b:3,4-b‘: 5,6-b‘‘]tripyran-2-one, 11,12-dihydro-12-hydroxy-6,6,10,11-tetramethyl-4-phenyl-, [10S-(10α,11β, 12β)]-; CAS Registry No. 65025-62-9} and cordatolide B, two of these dipyranocoumarins, were converted to α-methoxy-α-(trifluoromethyl)phenylacetate (MTPA) derivatives and investigated by 1H NMR spectroscopy. A correlation of 1H NMR chemical shift differences with those predicted by Mosher's concept alone was inadequate to assign confidently the absolute stereochemistries, due to the fact that in both of these molecules too few protons are present on one side of the MTPA plane. However, energetically favored conformations obtained by molecular mechanics calculations provided satisfactory rationalizations for the observed anisotropic shifts in 1H NMR data. The combined results of the two techniques allow us to assign the absolute configuration of both soulattrolide and cordatolide B as (10S,11R,12S). The absolute configurations of the other structurally related inhibitors, including inophyllums B, D, and P, costatolide, calanolides A, B, and C, and cordatolide A, are also assigned on the basis of chemical conversions and correlations of their chiroptical properties. Subtleties in the application of the Cahn−Ingold−Prelog rules to the designation of R or S configurations at some positions in these compounds make basically trivial errors particularly easy.