著者

瀧澤 俊也 成田 紘一 渡邉 一弘 阿部 秀樹 加藤 正 タキザワ トシヤ ナリタ コウイチ ワタナベ カズヒロ アベ ヒデキ カトウ タダシ Toshiya TAKIZAWA Koichi NARITA Kazuhiro WATANABE Hideki ABE Tadashi KATOH

雑誌

東北薬科大学研究誌

巻号頁・発行日

vol.54, pp.33-47, 2007-12

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Spiruchostatin A (1), isolated from a culture broth of Pseudomonas sp., has been shown to be a potent histone deacetylase (HDAC) inhibitor. HDAC inhibitors can suppress the growth of human tumor xenografts, this natural product, therefore, is expected to be a promising candidate for novel molecular-targeted anticancer agents. We envisioned that 1 would be synthesized through twofold macrolactam/macrolactone cyclization of the fully elaborated acyclic disulfide 2. The key segments 3 and 4, required for the preparation of the advanced key intermediate 2, were initially synthesized, and the two segments were subsequently subjected to the critical cross S-S coupling reaction to produce the desired key intermediate 11 (synthetically equivalent to 2). Upon deprotection of the N-Boc and the methyl ester groups in 11, the crucial cyclization formation was achieved using PyBOP to provide the desired macrolactam 16, a potential key precursor for 1. Further investigations concerning the transformation of 16 to the target molecule 1 were also described.

著者

渡邉 一弘 成田 紘一 佐藤 静香 加藤 正

出版者

日本薬学会化学系薬学部会

雑誌

反応と合成の進歩シンポジウム 発表要旨概要

巻号頁・発行日

vol.36, pp.139, 2010

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In multistep syntheses of complex natural products, selection of the most suitable protecting group for each hydroxy function is very important and sometimes holds the key to success. We are interested in the chemoselective deprotection to expand synthetic applicability of phenyliodine(III) bis(trifluoroacetate) (PIFA). The hypervalent iodine reagent such as PIFA is one of the promising reagent for development of environmentally benign oxidations. We describe not only the deprotection of more readily removable 3,4-dimethoxybenxyl (^3,4DMB) protecting groups, but also selectivity among the three benzyl-type protecting groups, ^3,4DMB, <I>p</I>-methoxybenzyl (PMB) and benzyl (Bn). When the tetra-protected compound (having Bn, PMB and ^3,4DMB groups) was treated with 2.0 equivalents of PIFA at room temperature, the ^3,4DMB group was removed to give mono-alcohol with more than 97% selectivity.