Synthesis of optically active phthaloyl D-aminooxy acids from L-amino acids or L-hydroxy acids as building blocks for the preparation of aminooxy peptides
Synthesis of optically active phthaloyl D-aminooxy acids from L-amino acids or L-hydroxy acids as building blocks for the preparation of aminooxy peptides
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DOI：
10.1021/jo0006573
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发表时间：
2000-11-03
影响因子：
3.6
通讯作者：
Yoon, J
中科院分区：
文献类型：
--
作者：
Shin, I;Lee, MR;Yoon, J
十多年来，许多生物有机化学家和合成化学家已经尝试制备具有新骨架结构的结构明确和/或生物活性的肽模拟物，用于产生新的二级和三级结构，以及用作重要药物受体和酶的激动剂、拮抗剂和酶抑制剂。1许多主链修饰的肽（假肽）如寡氨基甲酸酯、2类肽、3寡脲、4寡磺酰胺、5寡吡咯啉酮、6肽、7和平坦肽8已被合成并表征其新颖的结构和/或生物学功能。9最近，由R-氨氧基酸形成的肽的结构10和理论研究11被报道为一种新型的肽模拟物。结果表明，即使是短的R-氨氧基肽也可以采用新的二级结构，即八元氢键转角或NO转角。10，11为了提供具有更多结构多样性和潜在有用的生物学性质的R-氨基氧基肽，我们合成了几种具有非极性和极性侧链的光学活性邻苯二甲酰氨基氧基酸，作为从R-氨基酸和R-羟基酸制备不同R-氨基氧基肽的结构单元。10 b，12已经报道了制备邻苯二甲酰基R-氨基氧基酸或酯的几种方法，包括用N-羟基邻苯二甲酰亚胺（PhthN-OH）置换R-卤代酯或酸，13 R-重氮酯与PhthN-OH的反应，14和R-羟基酯与PhthN-OH的Mitsunobu反应，15。在已知的方法中，使用Mitsunobu反应，因为容易制备的R-羟基酯立体特异性转化为所需的邻苯二甲酰基R-氨基氧基酯，并转化构型。最初，含有未保护侧链的邻苯二甲酰D-氨基氧基酸（4）由相应的L-羟基酸（1）以三个步骤有效地制备，所述L-羟基酸（1）从商业供应商获得或通过在2.5NH2-SO 4或20%HOAc中用NaNO 2处理L-氨基酸而合成（方案1）。16铯的苄基化
For over a decade, many bioorganic and synthetic chemists have made attempts to prepare structurally well-defined and/or biologically active peptidomimetics with novel backbone structures for the creation of new secondary and tertiary structures, as well as for application as agonists, antagonists, and enzyme inhibitors for important pharmaceutical receptors and enzymes. 1 A number of backbone-modified peptides (pseudopeptides) such as oligocarbamates, 2 peptoids, 3 oligoureas, 4 oligosulfonamides, 5 oligopyrrolinones, 6-peptides, 7 and flat peptides8 have been synthesized and characterized for their novel structures and/or biological functions. 9 Recently, structural10 and theoretical studies11 of peptides formed by R-aminooxy acids have been reported as a new type of peptidomimetic. It was shown that even short R-aminooxy peptides could adopt a novel secondary structure, namely, eight-membered, hydrogen-bonded turns or NO turns. 10, 11 To provide access to R-aminooxy peptides with more structural diversity and potentially useful biological properties, we have synthesized several optically active phthaloyl aminooxy acids with nonpolar and polar side chains as building blocks for the preparation of diverse R-aminooxy peptides from R-amino acids and R-hydroxy acids. 10b, 12 Several methods for the preparation of phthaloyl R-aminooxy acids or esters, including displacement of an R-halo ester or acid with N-hydroxyphthalimide (PhthN-OH), 13 the reaction of an R-diazo ester with PhthN-OH, 14 and the Mitsunobu reaction of R-hydroxy ester with PhthN-OH, 15 have been reported. Among the known methods, the Mitsunobu reaction was employed because of the stereospecific conversion of easily prepared R-hydroxy esters to the desired phthaloyl R-aminooxy esters with the inversion of configuration. 15Initially, phthaloly D-aminooxy acids (4) containing unprotected side chains were effectively prepared in three steps from the corresponding L-hydroxy acids (1), which were obtained from commercial suppliers or synthesized by treatment of L-amino acids with NaNO2 in 2.5 NH 2-SO4 or 20% HOAc (Scheme 1). 16 Benzylation of cesium