Oxidative diversification of amino acids and peptides by small-molecule iron catalysis.
Oxidative diversification of amino acids and peptides by small-molecule iron catalysis.
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DOI：
10.1038/nature18941
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发表时间：
2016-09-08
期刊：
影响因子：
64.8
通讯作者：
White, M. Christina
中科院分区：
文献类型：
--
作者：
Osberger, Thomas J.;Rogness, Donald C.;Kohrt, Jeffrey T.;Stepan, Antonia F.;White, M. Christina
非核糖体肽合成酶 (NRPS) 合成的次级代谢物表现出多样化和复杂的拓扑结构，并具有令人印象深刻的生物活性范围。这种多样性很大程度上源自一种合成策略，该策略需要手性氨基酸构件和组装前和组装后的肽支架的氧化。万古霉素生物合成途径是一系列氧化转化的一个很好的例子，这些氧化转化可以由参与其生物合成的含铁酶进行。然而，由于使用此类氧化酶在体外进行化学转化存在挑战，以这些原理为指导的化学合成尚未在自然界之外完全实现。在这篇手稿中，我们报道了两种小分子铁催化剂能够促进氨基酸和肽的靶向CH氧化修饰，同时保留α中心手性。脯氨酸氧化为 5-羟基脯氨酸提供了一种多功能中间体，可以在单体和肽环境中转化为刚性芳基化衍生物或柔性直链羧酸、醇、烯烃和胺。这种CH氧化策略的价值体现在其产生多样性的能力：四个“手性库”氨基酸被转化为二十一个手性非天然氨基酸（UAA），代表七个不同的功能组阵列；单个含脯氨酸三肽的后期CH功能化提供了八个三肽，每个三肽具有不同的UAA。此外，含有脯氨酸转角元件的大环肽通过后期CH氧化转化为含有线性UAA的大环肽。
Secondary metabolites synthesized by nonribosomal peptide synthetases (NRPSs) display diverse and complex topologies and possess an impressive range of biological activities Much of this diversity derives from a synthetic strategy that entails the oxidation of both the chiral amino acid building blocks and the assembled peptide scaffolds pre- and post-assembly. The vancomycin biosynthetic pathway is an excellent example of the range of oxidative transformations that can be performed by the iron-containing enzymes involved in its biosynthesis. However, because of the challenges associated with using such oxidative enzymes to carry out chemical transformations in vitro, chemical syntheses guided by these principles have not been fully realized outside of nature. In this manuscript, we report that two small-molecule iron catalysts are capable of facilitating the targeted C—H oxidative modification of amino acids and peptides with preservation of α-center chirality. Oxidation of proline to 5-hydroxyproline furnishes a versatile intermediate that can be transformed to rigid arylated derivatives or flexible linear carboxylic acids, alcohols, olefins, and amines in both monomer and peptide settings. The value of this C—H oxidation strategy is demonstrated in its capacity for generating diversity: four 'chiral pool' amino acids are transformed to twenty-one chiral unnatural amino acids (UAAs) representing seven distinct functional group arrays; late-stage C—H functionalizations of a single proline-containing tripeptide furnish eight tripeptides, each having different UAAs. Additionally, a macrocyclic peptide containing a proline turn element is transformed via late-stage C—H oxidation to one containing a linear UAA.
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影响因子：
56.9
作者：
Chen, Mark S.;White, M. Christina
通讯作者：
White, M. Christina
影响因子：
16.6
作者：
Seiple, Ian B.;Mercer, Jaron A. M.;Sussman, Robin J.;Zhang, Ziyang;Myers, Andrew G.
通讯作者：
Myers, Andrew G.
影响因子：
8.4
作者：
Yudin AK
通讯作者：
Yudin AK
DOI：
10.1016/0006-291x(90)91463-3
发表时间：
1990-05-31
影响因子：
3.1
作者：
UCHIDA, K;KATO, Y;KAWAKISHI, S
通讯作者：
KAWAKISHI, S
影响因子：
15
作者：
Gormisky, Paul E.;White, M. Christina
通讯作者：
White, M. Christina