Glucosamine and glucosamine-6-phosphate derivatives: catalytic cofactor analogues for the glmS ribozyme.
Glucosamine and glucosamine-6-phosphate derivatives: catalytic cofactor analogues for the glmS ribozyme.
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DOI：
10.1021/jo400192e
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发表时间：
2013-05-17
期刊：
影响因子：
--
通讯作者：
Ferré-D'Amaré AR
中科院分区：
文献类型：
--
作者：
Posakony JJ;Ferré-D'Amaré AR
制备了两个葡萄糖胺-6-磷酸类似物（GlcN6P, 1）和五个葡萄糖胺类似物（GlcN, 2）作为glmS核酶的催化辅助因子进行评价，glmS核酶是一种控制细胞壁生物合成的细菌基因调控RNA。分别以1,2,4,6保护糖为原料，通过SN2反应制备了3-叠氮取代的氨基葡萄糖和异丙胺；最终的酸水解产生完全去保护的化合物作为TFA盐。葡萄糖胺经过13步合成制备了6-磷酸-2-氨基葡萄糖内酰胺（31），其中包括后期pocl3磷酸化。采用三乙基硅基（TES）保护基团，建立了一种简单且广泛适用的两步程序，选择性地暴露n保护的氨基葡萄糖类似物中的6-OH基团，这为化学磷酸化提供了另一种途径。光信化学提供了GlcN-(Cbz)的6-氰基（35）和6-叠氮基（36）类似物，并通过NMR （COSY， HMBC， HMQC）实验证实了6-位置的选择性。化合物36被转化为完全去保护的6-叠氮- glcn（37）和2,6-二氨基葡萄糖（38）类似物。通过恶氮吡啶制备了2-羟胺葡萄糖（42）类似物（41）。42的酶促磷酸化和6-OH前体（43）的化学磷酸化是可能的，但42和6-磷酸产物（44）在中性或碱性条件下是不稳定的。先前描述的2-胍基葡萄糖的化学磷酸化（46）在最终去保护后提供了其6-磷酸类似物（49）。
Two analogues of glucosamine-6-phosphate (GlcN6P, 1) and five of glucosamine (GlcN, 2) were prepared for evaluation as catalytic cofactor of the glmS ribozyme, a bacterial gene-regulatory RNA that controls cell wall biosynthesis. Glucosamine and allosamine with 3-azido substitutions were prepared by SN2 reactions of the respective 1,2,4,6-protected sugars; final acidic hydrolysis afforded the fully deprotected compounds as their TFA salts. A 6-phospho-2-aminoglucolactam (31) was prepared from glucosamine in a 13-step synthesis, which included a late-stage POCl3-phosphorylation. A simple and widely applicable 2-step procedure with the triethylsilyl (TES) protecting group was developed to selectively expose the 6-OH group in N-protected glucosamine analogs, which provided another route to chemical phosphorylation. Mitsunobu chemistry afforded 6-cyano (35) and 6-azido (36) analogues of GlcN-(Cbz) and the selectivity for the 6-position was confirmed by NMR (COSY, HMBC, HMQC) experiments. Compound 36 was converted to the fully deprotected 6-azido-GlcN (37) and 2,6-diaminoglucose (38) analogs. A 2-hydroxylamino glucose (42) analogue was prepared via an oxaziridine (41). Enzymatic phosphorylation of 42 and chemical phosphorylation of its 6-OH precursor (43) were possible, but 42 and the 6-phospho product (44) were unstable under neutral or basic conditions. Chemical phosphorylation of the previously described 2-guanidinyl-glucose (46) afforded its 6-phospho analogue (49) after final deprotection.
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影响因子：
18.3
作者：
Deigan, Katherine E.;Ferre-D'Amare, Adrian R.
通讯作者：
Ferre-D'Amare, Adrian R.
影响因子：
1.1
作者：
HANESSIAN, S;MASSE, R;NAKAGAWA, T
通讯作者：
NAKAGAWA, T
DOI：
10.1073/pnas.0811481106
发表时间：
2009-01-06
影响因子：
11.1
作者：
Laughlin, Scott T.;Bertozzi, Carolyn R.
通讯作者：
Bertozzi, Carolyn R.
影响因子：
2.1
作者：
OVERKLEEFT, HS;VANWILTENBURG, J;PANDIT, UK
通讯作者：
PANDIT, UK
DOI：
10.1002/cber.19741070624
发表时间：
1974-01-01
期刊：
CHEMISCHE BERICHTE-RECUEIL
影响因子：
--
作者：
PAULSEN, H;GRAGE, U
通讯作者：
GRAGE, U