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首页> 外文期刊>Chemistry: A European journal >Concise approach to the 'higher sugar' core of the nucleoside antibiotic hikizimycin
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Concise approach to the 'higher sugar' core of the nucleoside antibiotic hikizimycin

机译：核苷类抗生素hizizimycin的“高糖”核心的简便方法

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摘要

A highly productive synthesis of phenylthio glycoside 33 is described which constitutes a fully functional surrogate for the hikosamine core of hikizimycin 1, a complex nucleoside antibiotic endowed with promising anthelmintic properties. The chosen approach to this undecose derivative starts from mannofuranose 7 which was one-carbon homologated to alkyne 8 in one step on treatment with lithio (trimethylsilyl)diazomethane. Alkynyl iodide 12 derived from 8 was combined with the tartrate-derived aldehyde 17 by a Nozaki-Hiyama-Kishi reaction that can either be performed using overstoichiometric amounts of CrCl2 or by means of a catalytic manifold based on the turnover of a cat. CrCl2/chlorosilane/manganese redox couple. Semi-hydrogenation of the resulting alkyne 18 to (Z)-olefin 19 required the use of Pd/C as the catalyst, whereas conventional Lindlar reduction was unsatisfactory. Attempted cis-dihydroxylation of alkene 22 (formed from 19 by a Mitsunobu reaction with phthalimide) by using catalytic amounts of OsO4 and NMO as the stoichiometric oxidant essentially failed, whereas a stoichiometric osmylation afforded the stable osmate ester 26a as a single diastercomer. Since the use of OsO4 in stoichiometric amounts deemed inappropriate for a total synthesis project, recourse was taken to catalytic "Blitz dihydroxylation" with RuO, in the presence of FeCl(2)(.)4H(2)O as co-catalyst. Application of these conditions to alkene 30 bearing a free aldehyde function at the terminus of the "higher sugar" chain furnished pyranose 32 in good yield and excellent diastereoselectivity, which was converted into the targeted thioglycoside 33 on treatment with PhSSPh/Et3P. It is particularly noteworthy that the conformational constraints of the acyclic substrate 30 enforce the dihydroxylation to violate Kishi's empirical rule for transformations of this type.
机译：描述了苯硫糖苷33的高产合成，其构成了hizizimycin 1的hikosamine核心的全功能替代物，hikizimycin 1是一种具有希望的驱虫特性的复杂核苷抗生素。选择这种十一烷衍生物的方法是从甘露呋喃糖7开始，甘露呋喃糖7在用硫代（三甲基甲硅烷基）重氮甲烷处理的一个步骤中与炔烃8碳原子同化。通过Nozaki-Hiyama-Kishi反应将衍生自8的炔基碘化物12与酒石酸衍生的醛17合并，该反应可以使用化学计量过量的CrCl2或基于猫的周转量的催化歧管来进行。 CrCl2 /氯硅烷/锰氧化还原对。将所得炔烃18半氢化为（Z）-烯烃19需要使用Pd / C作为催化剂，而常规的Lindlar还原是不令人满意的。通过使用催化量的OsO4和NMO作为化学计量的氧化剂尝试进行烯烃22的顺式二羟基化反应（由19与邻苯二甲酰亚胺的Mitsunobu反应形成）基本上失败了，而化学计量的甲磺酰化作用则得到了稳定的膦酸酯26a作为单一的非对映异构体。由于以化学计量的量使用OsO4被认为不适合用于总合成项目，因此在FeCl（2）（。）4H（2）O作为助催化剂的情况下，采用RuO催化了“ Blitz二羟基化”。将这些条件应用于在“高级糖”链末端具有游离醛功能的烯烃30上，吡喃糖32具有良好的产率和非对映选择性，在用PhSSPh / Et3P处理后转化为目标硫代糖苷33。特别值得注意的是，无环底物30的构象约束迫使二羟基化违反了Kishi关于这种类型转化的经验规则。

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