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.
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.
Shevyakov
Sergey V
SV
Chemical Diversity Research Institute, Khimki, Moscow Reg., 114401 Russia.
Davydova
Olga I
OI
Kiselyov
Alex S
AS
Kravchenko
Dmitry V
DV
Ivachtchenko
Alexandre V
AV
Krasavin
Mikhail
M
D000470:Alkaloids / Q000737:chemistry*; D008401:Gas Chromatography-Mass Spectrometry; D007659:Ketones / Q000737:chemistry*; D008094:Lithium / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D011799:Quinazolines / Q000737:chemistry*; D013237:Stereoisomerism
D000470:Alkaloids; D007659:Ketones; D011799:Quinazolines; C019592:vasicine; D008094:Lithium