Glycal glycosylation and 2-nitroglycal concatenation, a powerful combination for mucin core structure synthesis
Glycal glycosylation and 2-nitroglycal concatenation, a powerful combination for mucin core structure synthesis
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DOI：
10.1021/jo061670b
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发表时间：
2007-06-08
影响因子：
3.6
通讯作者：
Schmidt, R. R.
中科院分区：
文献类型：
--
作者：
Geiger, Juergen;Reddy, B. Gopal;Schmidt, R. R.
具有大量6-O-TIPS保护的3,4-O无保护的半乳糖衍生物（化合物2）可以与O-（半乳糖酰基）三氯乙酸酯选择性地3-O糖基化；根据保护基团的模式，可以得到立体选择性的-和-连接双糖。以O-（2-叠氮-2-脱氧葡萄糖吡喃基）三氯乙酸酯为供体（化合物10A），以乙腈为溶剂，将2和6-O无保护的半乳糖衍生物糖基化，分别得到(1-3)-和(1-6)-连接的双糖。对糖的半乳糖部分进行硝化，然后添加michael型的丝氨酸和苏氨酸衍生物（7a,b），安装了α -半乳糖构型，从而很容易为将核心1、核心2、核心3、核心6和核心8结构整合到糖肽中提供o-糖基氨基酸构建块。2-硝基半乳糖和2-硝基葡萄糖衍生物也可以通过michael型加成以重复的方式成功地用于糖苷键形成，提供相应的核心5，核心7和核心6构建块。在这种方法中，高度立体选择性的糖苷键形成完全基于对2-硝基糖的硝基烯醇醚部分的michael型加成。因此，2-硝基甘油是碱催化糖苷键形成的通用中间体。
A 3,4-O-unprotected galactal derivative having bulky 6-O-TIPS protection (compound 2) could be regioselectively 3-O-glycosylated with O-(galactopyranosyl) trichloroacetimidates; depending on the protecting group pattern stereoselectively alpha- and beta-linked disaccharides were obtained. With O-(2-azido-2-deoxyglucopyransyl) trichloroacetimidate as donor (compound 10A), glycosylation of 2 and of a 6-O-unprotected galactal derivative led in acetonitrile as solvent exclusively to a beta(1-3)- and a beta(1-6)-linked disaccharide, respectively. Nitration of the galactal moieties of the saccharides followed by Michael-type addition of serine and threonine derivatives (7a,b) installed the alpha-galacto-configuration, thus readily furnishing O-glycosyl amino acid building blocks for the incorporation of core 1, core 2, core 3, core 6, and core 8 structures into glycopeptides. 2-Nitrogalactal and 2-nitroglucal derivatives could be also successfully employed in glycoside bond formation via Michael-type addition in a reiterative manner, affording the corresponding core 5, core 7, and core 6 building blocks. In this approach, highly stereoselective glycoside bond formations were based exclusively on Michael-type addition to the nitro-enol ether moiety of the 2-nitroglycals. Hence, 2-nitroglycals are versatile intermediates for base-catalyzed glycoside bond formation.