Asymmetric synthetic study of macrolactin analogues |
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Authors: | Yusuke Kobayashi Tetsutaro Kimachi Yoshiji Takemoto |
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Affiliation: | a Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan b Faculty of Pharmaceutical Sciences, Mukogawa Women's University, 11-68 Koshien Kyuban-cho, Nishinomiya 663-8179, Japan |
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Abstract: | We designed two aromatic analogues 1a and 1b of macrolactin A with expectation of enhancing biological activity and metabolical stability. As a result of retrosynthetic analysis of these compounds 1a-b, two synthetic strategies have been examined. The first strategy includes the enantioselective addition of nonadienyl anion, derived from 3, to aldehyde 4 as a key step. The second one includes epimerization of ynone 7 to (E,E)-conjugated dienone 31 and subsequent diastereoselective hydride-reduction of 31. Although the former route furnished no desired target, the latter one was revealed to work well for the synthesis of 1. Unfortunately, the aimed (2Z,4E)-analogue 1a could not be synthesized due to an epimerization of the (2Z)-olefin into the (2E)-olefin. However, these methods could be applied to the total asymmetric synthesis of the (2E,4E)-analogue 1b. Overall, control of all of the four stereocenters was achieved by means of asymmetric and diastereoselective reactions without using any chiral natural sources. |
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Keywords: | Macrolactin A Antibiotics Antivirus Asymmetric synthesis Ynone Isomerization (E,E)-Conjugated dienone |
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