Hantzsch-type three-component approach to a new family of carbon-linked glycosyl amino acids. synthesis of C-glycosylmethyl pyridylalanines
Hantzsch-type three-component approach to a new family of carbon-linked glycosyl amino acids. synthesis of C-glycosylmethyl pyridylalanines
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DOI：
10.1021/jo071221r
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发表时间：
2007-09-28
影响因子：
3.6
通讯作者：
Aldhoun, Mohammad
中科院分区：
文献类型：
--
作者：
Dondoni, Alessandro;Massi, Alessandro;Aldhoun, Mohammad
[图形]本文报道的C-糖基甲基吡啶基丙氨酸构成了一个新的糖基氨基酸家族，其中含有连接碳水化合物和氨基酸残基的吡啶环。这些氨基酸可用于制备非天然糖肽，其通过刚性和高度稳定的系链显示牢固结合的碳水化合物片段。一个可行的路线，这些新的混合分子已经打开了通过热诱导的Hantzsch型环化缩合使用的双酯-酮酯-烯氨基酯系统。其中一种试剂上连接着C-糖基残基，而另一种试剂上则结合着氨基酸片段。在一锅优化方法中，不分离二氢吡啶，而通过使用聚合物负载的清除剂除去未反应的材料和副产物来进行其纯化。然后，二氢吡啶（非对映异构体的混合物）被聚合物结合的氧化剂氧化，得到带有两个生物活性残基的目标吡啶。以这种方式，制备了一系列的八种化合物（58-68%产率），其中多样性的元素是（i）吡喃糖环的葡萄糖和半乳糖构型，（ii）异头中心的α-和β-构型，以及（iii）吡啶环中碳水化合物和氨基酸部分的位置。这些氨基酸中的正交官能团保护允许它们通过顺序的氨基和羧基偶联容易地掺入寡肽中。
[GRAPHICS]C-Glycosylmethyl pyridylalanines reported in this paper constitute a novel family of glycosyl amino acids that contain a pyridine ring linking the carbohydrate and amino acid residues. These amino acids may serve to prepare nonnatural glycopeptides displaying firmly bound carbohydrate fragments through a rigid and highly stable tether. A viable route to these new hybrid molecules has been opened via thermally induced Hantzsch-type cyclocondensation using an aldehyde-ketoester-enamino ester system. To one of these reagents was attached a C-glycosyl residue, while to another was bound an amino acid fragment. In a one-pot optimized methodology, the dihydropyridine was not isolated while its purification was carried out by removal of unreacted material and side products using polymer-supported scavengers. Then the dihydropyridine (mixture of diastereoisomers) was oxidized by a polymer-bound oxidant to give the target pyridine bearing the two bioactive residues. In this way a range of eight compounds (58-68% yield) was prepared in which the elements of diversity were (i) the gluco and galacto configurations of the pyranose ring, (ii) the alpha- and beta-configurations at the anomeric center, and (iii) the positions of the carbohydrate and amino acid sectors in the pyridine ring. The orthogonal functional group protection in these amino acids allowed their easy incorporation into oligopeptides via sequential amino and carboxylic group coupling.