Natural products as templates for bioactive compound libraries: part 2. Novel modifications of vasicine (peganine) core via efficient and regioselective generation of 3-lithiodeoxyvasicine and its stereoselective addition to aliphatic ketones section sign.

Sergey V Shevyakov, Olga I Davydova, Alex S Kiselyov, Dmitry V Kravchenko, Alexandre V Ivachtchenko, Mikhail Krasavin

Index: Nat. Prod. Res. 20(9) , 871-81, (2006)

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Abstract

A general procedure for direct lithiation of deoxyvasicine was developed. 3-Lithiodeoxyvasicine intermediate was found to react with various aliphatic ketones providing derivatives of 3-(hydroxyalkyl)deoxyvasicine in good yields. Similar reaction with 4-alkylcyclohexanones yielded respective trans-adducts exclusively. This novel protocol was successfully scaled-up to result in multigram quantities of vasicine-containing core building blocks suitable for production of compound libraries. The described synthetic methodology offers access to a wide range of compounds with potentially beneficial biological profiles.