TY - JOUR
T1 - Absolute stereochemistry of soulattrolide and its analogues
AU - Shi, Xiongwei
AU - Attygalle, Athula B.
AU - Liwo, Adam
AU - Hao, Ming Hong
AU - Meinwald, Jerrold
AU - Dharmaratne, H. Ranjith W.
AU - Wanigasekera, W. M.Anoja P.
PY - 1998/2/20
Y1 - 1998/2/20
N2 - 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.
AB - 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.
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U2 - 10.1021/jo9717752
DO - 10.1021/jo9717752
M3 - Article
AN - SCOPUS:0032549044
SN - 0022-3263
VL - 63
SP - 1233
EP - 1238
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
IS - 4
ER -