Synthesis of Tunicaminyluracil Derivatives
Synthesis of Tunicaminyluracil Derivatives
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DOI：
10.1081/ncn-120027831
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发表时间：
2004-01
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以二碘化钐（SmI 2）为催化剂，通过Aldol反应和分子内Pummerer反应合成了衣霉素核苷类抗生素的关键成分衣胺尿嘧啶衍生物。α-苯硫基酮11是钐烯醇化物的前体，由d-半乳糖制备。在− 40°C下用SmI 2处理11，使其完全转化为相应的钐烯醇化物，随后加入尿苷5′-醛12，得到所需的羟醛产物13 a，b。化合物13 a通过酮的顺序非对映选择性还原和用mCPBA氧化转化为亚砜15。用Tf 2 O活化15得到所需的环化化合物17。在该反应中，由于通过7元环中间体的DMSO-氧化的竞争性分子内形式，也获得了羟醛产物13 a。化合物18或19可用作糖基化中的糖基供体，以提供一系列类似物作为潜在的糖基转移酶抑制剂以及相关的天然产物。[2]为了荣誉和庆祝勒罗伊教授B的70岁生日。汤森。#本文构成核苷和核苷酸的第225部分：Shuto，S.; Fukuoka，M.; Kudoh，T.; Garnham，C.; Galione，A.;波特，B。V.L.; Matsuda，A. J.Med.Chem.2003，46，4741中。
A tunicaminyluracil derivative, which is a key component of the tunicamycin nucleoside antibiotics, was synthesized using a samarium diiodide (SmI2) mediated aldol reaction and intramolecular Pummerer reaction as the key steps. The α‐phenylthio ketone 11, the precursor of the samarium enolate, was prepared from d‐galactose. Treatment of 11 with SmI2 at − 40°C resulted in complete conversion to the corresponding samarium enolate, and subsequent addition of uridine 5′‐aldehyde 12 afforded the desired aldol products 13a,b. Compound 13a was converted to the sulfoxide 15 by a sequential diastereoselective reduction of the ketone and an oxidation with mCPBA. Activation of 15 with Tf2O provided the desired cyclized compound 17. In this reaction, the aldol product 13a was also obtained as a consequence of a competitive intramolecular version of DMSO‐oxidation via a 7‐membered ring intermediate. Compound 18 or 19 are ready for use as a glycosyl donor in glycosylations to provide a range of analogues as potential glycosyltransferase inhibitors as well as related natural products. †In honor and celebration of the 70th birthday of Professor Leroy B. Townsend. #This paper constitutes Part 225 of Nucleosides and Nucleotides: Shuto, S.; Fukuoka, M.; Kudoh, T.; Garnham, C.; Galione, A.; Potter, B. V. L.; Matsuda, A. J. Med. Chem. 2003, 46, 4741.