Determination of Absolute Configuration of Stereogenic Carbinol Centers in Annonaceous Acetogenins by 1H- and 19F-NMR Analysis of Mosher Ester Derivatives

Matthew J. Rieser, Yu hua Hui, J. Kent Rupprecht, John F. Kozlowski, Karl V. Wood, Jerry L. McLaughlin, Paul R. Hanson, Zhiping Zhuang, Thomas R Hoye

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Abstract

The absolute configuration of the stereogenic carbinol centers in nine annonaceous acetogenins has been determined by careful 1H- and 19F-NMR analysis of (S)- and (R)-Mosher ester [methoxy(trifluoromethyl)phenylacetate or MTPA] derivatives. These acetogenins include five adjacent bis-tetrahydrofuran acetogenins [uvaricin (3), bullatacin (4), bullatacinone (5), asimicin (6), and rolliniastatin 1 (7)] and four mono-tetrahydrofuran acetogenins [reticulatacin (8), isoannonacin-10-one (9), annonacin-10-one (10), and annonacin (11)]. Importantly, the configuration at the C(4) carbinol center in all of the biologically most significant acetogenins examined here is R. The validity of the refined Mosher methodology8c for assigning absolute carbinol stereochemistry in several specific substructural regions of these acetogenins was established by analysis of the MTPA esters of appropriate synthetic model compounds. These possessed unambiguous absolute (as well as relative) stereochemistry. It was demonstrated that the analysis of proton and fluorine NMR data from atoms flanking carbinol centers is always a valid strategy for assigning absolute configuration at any of the carbinol centers, given the availability of suitable model compounds of known absolute configuration. The interpretation of the fluorine NMR data, however, must be performed with caution. Although there are clearly identifiable trends among the fluorine data, whether they are indicative of R or S absolute configuration is dependent upon quite subtle local structural features.

Original languageEnglish (US)
Pages (from-to)10203-10213
Number of pages11
JournalJournal of the American Chemical Society
Volume114
Issue number26
DOIs
StatePublished - Dec 1 1992

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