Absolute configuration of neostenine.pdfVIP

Journal of Molecular Structure 966 (2010) 18–22Contents lists available at ScienceDirect Journal of Molecular Structure journal homepage: www.elsevier .com/locate /molstrucAbsolute configuration of neostenine Ren-Wang Jiang a,*, Wencai Ye a, Pang-Chui Shaw b, Paul Pui-Hay But b, Thomas C.W. Mak b aKey Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicines and New Drug Research, College of Pharmacy, Jinan University, Guangzhou, PR China bDepartment of Biochemistry, Biology, and Chemistry, The Chinese University of Hong Kong, Hong Kong, PR China a r t i c l e i n f o a b s t r a c tArticle history: Received 28 September 2009 Received in revised form 29 November 2009 Accepted 29 November 2009 Available online 4 December 2009 Keywords: Neostenine Stemona alkaloid Absolute configuration0022-2860/$ - see front matter  2009 Elsevier B.V. A doi:10.1016/j.molstruc.2009.11.059 * Corresponding author. Tel.: +86 20 8522 1016; fa E-mail address: rwjiang2008@ (R.-WHeavy atoms bromine and iodine were incorporated into the neostenine (1) skeleton through reductive cleavage of the lactone ring, followed by acylation with 4-bromobenzoyl chloride, and salt formation with methyl iodide, respectively. The absolute configuration of the seven chiral centers C1, C9, C9a, C10, C11, C1 and C13 in 1 were assigned as S, S, R, R, R, R, and S, respectively, based on the Flack param- eters in X-ray structure refinement, and results from the two heavy atom derivatives are consistent with each other. As many Stemona alkaloids share the same lactone and pyrrolo[1,2-a]azepine nucleus as those in 1, the facile method reported in this paper can be applied for the determination of absolute con- figurations of similar alkaloids.  2009 Elsevier B.V. All rights reserved.1. Introduction Anomalous scattering of X-ray by heavy atoms has long been employed as the most reliable method for determining the abso- lute configuration of chiral molecules [1] based on Flack parame- ters [2]. How