3‐Hydroxyazetidine Carboxylic Acids: Non‐Proteinogenic Amino Acids for Medicinal Chemists
3‐Hydroxyazetidine Carboxylic Acids: Non‐Proteinogenic Amino Acids for Medicinal Chemists
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DOI：
10.1002/cmdc.201200541
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发表时间：
2013-04
期刊：
影响因子：
3.4
通讯作者：
Andreas F. G. Glawar;S. F. Jenkinson;A. Thompson;S. Nakagawa;A. Kato;T. Butters;G. Fleet
中科院分区：
文献类型：
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作者：
Andreas F. G. Glawar;S. F. Jenkinson;A. Thompson;S. Nakagawa;A. Kato;T. Butters;G. Fleet
由D-葡萄糖形成2，4-二脱氧-2，4-亚氨基核糖酸的两种对映体是未保护的3-羟基氮杂环丁烷羧酸的第一次化学合成。3-羟基氮杂环丁烷酰胺在酸性和中性pH下的长期稳定性已经确立，这意味着它们作为肽的非蛋白质氨基酸组分的价值，为药物化学家提供了一类新的肽电子等排体。通过X射线晶体学分析确定了N，3-O-二苄基-2，4-二脱氧-2，4-亚氨基-D-核糖酸的结构。N-甲基氮杂环丁烷酰胺衍生物是β-氨基己糖苷酶在微摩尔水平的特异性抑制剂，并且仅是与亚氨基糖相关的糖氨基酸的酰胺对任何糖苷酶的有效抑制的第二个实例。
The formation from D‐glucose of both enantiomers of 2,4‐dideoxy‐2,4‐iminoribonic acid is the first chemical synthesis of unprotected 3‐hydroxyazetidine carboxylic acids. The long‐term stability of 3‐hydroxyazetidine amides is established at acidic and neutral pH and implies their value as non‐proteinogenic amino acid components of peptides, providing medicinal chemists with a new class of peptide isosteres. The structure of N,3‐O‐dibenzyl‐2,4‐dideoxy‐2,4‐imino‐D‐ribonic acid was established by X‐ray crystallographic analysis. An N‐methylazetidine amide derivative is a specific inhibitor of β‐hexosaminidases at the micromolar level, and is only the second example of potent inhibition of any glycosidase by an amide of a sugar amino acid related to an iminosugar.