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N. A. Zefirov, Y. S. Glazkova, I. V. Kuznetsova, E. V. Nurieva, O. N. Zefirova
(Division of medicinal chemistry and advanced organic synthesis)
Moleculardesignandan attempt of synthesis of2-methoxyestradiol conjugate with adamantane
Abstract
2-Adamantyl-8-[(2-methoxy-estra-1,3,5(10)-trien-3,17β-diol-6α-yl)-amino] octanoate (2d) was
proposed as a structural analogue of highly cytotoxic N-(8-(adamant-2-yloxi)-8-oxooctanoyl)-N-deacetylcolchycine
based on molecular modeling data. The three-step synthesis of
adamant-2-yl-8-amino octanoate (5) is described. The reductive amination of
2-methoxy-6-oxo-17β-estradiol in the presence of
compound 5, NaBH3CN or Na(OAc)3BH in slightly acidic
media afforded not the conjugate 2d, but the product of elimination at the C6–C7
bond of the steroid 7.
Key words: tubulin, colchicine, adamantane,
2-methoxyestradiol, reductive amination.
Copyright (C) Chemistry Dept., Moscow State University, 2002
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