Total Synthesis of Bistramide A and Its 36(Z) Isomers: Differential Effect on Cell Division,Differentiation, and Apoptosis |
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| Authors: | Dr Loïc Tomas Dr Gustav Boije?af?Gennäs Dr Marie Aude Hiebel Dr Peter Hampson Dr David Gueyrard Dr Béatrice Pelotier Prof Jari Yli‐Kauhaluoma Prof Olivier Piva Prof Janet M Lord Prof Peter G Goekjian |
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| Institution: | 1. Université de Lyon, ICBMS ‐ UMR CNRS 5246, LCO2 ‐ Glycochimie, Université Claude Bernard Lyon 1, Bat. 308 CPE Lyon, 43, bd du 11 Novembre 1918, 69622 Villeurbanne Cedex (France), Fax: (+33)?472 43 2752;2. Division of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Helsinki, PO Box 56 (Viikinkaari 5 E), 00014 Helsinki (Finland);3. Université de Lyon, ICBMS ‐ UMR CNRS 5246, Surcoof, Université Claude Bernard Lyon 1, Bat. Raulin, 43, bd du 11 Novembre 1918, 69622 Villeurbanne Cedex (France);4. School of Immunity and Infection, The Medical School, University of Birmingham, Birmingham B15?2TT (UK) |
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| Abstract: | The total synthesis of bistramide A and its 36(Z),39(S) and 36(Z),39(R) isomers shows that these compounds have different effects on cell division and apoptosis. The synthesis relies on a novel enol ether‐forming reaction for the spiroketal fragment, a kinetic oxa‐Michael cyclization reaction for the tetrahydropyran fragment, and an asymmetric crotonylation reaction for the amino acid fragment. Preliminary biological studies show a distinct pattern of influence of each of the three compounds on cell division, differentiation, and apoptosis in HL‐60 cells, thus suggesting that these effects are independent activities of the natural product. |
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| Keywords: | alkenes bistramide A protein kinase C total synthesis |
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