synthesis of cyclophellitol utilizing a palladium chloride mediated-ferrier-ii rearrangement合成cyclophellitol利用氯化钯mediated-ferrier-ii重排.pdfVIP

Molecules 2005, 10, 901-911 molecules ISSN 1420-3049 Synthesis of Cyclophellitol Utilizing a Palladium Chloride Mediated-Ferrier-II Rearrangement Hideyo Takahashi and Shiro Ikegami *,# Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199-0195, Japan. Tel. +81-426-85-3728, Fax. +81-426-85-1872 * Author to whom correspondence should be addressed; e-mail. shi-ike@pharm.teikyo-u.ac.jp # Dedicated to Professor K. K. Balasubramanian on the occasion of his sixty fifth birthday. Received: 2 January 2005 / Accepted: 5 January 2005 / Published: 31 August 2005 Abstract: Cyclophellitol and its C3-epimer have been synthesized from 5-enoglucopyranoside and 5-enomannopyranoside, respectively. The carbocyclic skeleton was constructed through a Ferrier-II reaction meditated by PdCl2 . Keywords: Glycosidase inhibitor, Ferrier-II reaction, palladium chloride. Introduction Since Ferrier developed a cyclization of saccharides using mercurate [Ferrier-II reaction] in 1979 [1], the ring conversion of 6-membered rings using saccharides has been intensively studied [2, 3]. Because naturally occurring and biologically active compounds often contain a ring structure with multi-functional groups, stereochemical control of chiral centers on these rings becomes crucial in the total synthesis of these compounds. The Ferrier-II reaction is remarkably useful for the total synthesis of compounds with a complicated conformation such as cyclitols. Cyclophellitol is a β-D-glucosidase inhibitor first isolated by Umezawa in 1990 [4]. It is known to have high activity, an