Stereoselective Hydroxylation Reactions
Stereoselective Hydroxylation Reactions
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DOI：
10.1002/chin.200121255
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发表时间：
2001-05
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影响因子：
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通讯作者：
H. Holland
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文献类型：
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作者：
H. Holland
传统的生物催化羟基化过程涉及C-H键的直接氧化以产生醇（图1），并且可以与其他生物催化反应区分开来，因为没有类似的单步化学过程可以在产物形成的区域或立体选择性方面与生物催化反应竞争。该反应在20世纪50年代首次应用于通过根霉属物种在C-11 a处羟基化孕酮来生产皮质类固醇[1]，是最早商业化利用的生物转化方法之一。原始工艺的改进版本至今仍在使用，并在此期间通过涉及不同基质的许多其他示例进行了补充。立体选择性生物催化羟基化作为一种方法，用于制备手性醇的直接氧化的一个特定的CH键的基板的价值，确保了在这一领域的持续研究，本章将涵盖显着的发展，在过去十年中，在羟基化反应领域，产生立体化学定义的产品从非手性基板。在此期间，仅在公开文献中就出现了700多篇关于生物催化羟基化的参考文献。因此，本章的内容将有选择性，但可以获得更全面的总结：羟基化反应已被包括在生物催化反应的几个一般综述中[2-4]，并且一直是一本致力于氧化酶生物转化的书的主题[5]。羟化酶绝大多数酶催化的立体选择性羟基化是由细胞色素P450依赖性单加氧酶进行的[4]。大多数这些酶的膜结合性质，连同它们对辅因子及其相关电子传递蛋白的存在的功能依赖性，确保了制备性生物催化羟基化最有效地用全细胞催化剂进行。这种普遍性的例外，脂氧合酶和卤代过氧化物酶，将在
The conventional biocatalytic hydroxylation process involves the direct oxidation of a C-H bond to produce an alcohol (Fig. 1) and may be distinguished from other biocatalytic reactions in that no analogous single-step chemical process can compete with the biocatalytic reaction in terms of the regio-or stereoselectivity of product formation. This reaction, first applied to the production of the corticosteroids in the 1950s via the hydroxylation of progesterone at C-11a by Rhizopus species [1], was one of the earliest biotransformation processes to be commercially exploited. Improved versions of the original process remain in use to this day and have been supplemented during the intervening period by many other examples involving different substrates. The value of stereoselective biocatalytic hydroxylation as a method for the preparation of chiral alcohols by the direct oxidation of a specific CH bond of the substrate has ensured continued research in this area, and this chapter will cover significant developments during the last decade in the field of hydroxylation reactions that produce stereochemically defined products from achiral sub-strates. During this period over 700 references dealing with biocatalytic hydroxylations have appeared in the open literature alone. Of necessity, therefore, this chapter will be selective in its coverage, but more comprehensive summaries are available: the hydroxylation reaction has been included in several general reviews of biocatalytic reactions [2-4] and has been the subject of a book dedicated to biotransformations with oxidative enzymes [5].1. Hydroxylase Enzymes The vast majority of enzyme-catalyzed stereoselective hydroxylations are carried out by the cytochrome P450-dependent monoxygenases [4]. The membrane-bound nature of the majority of these enzymes, together with their functional dependence on the presence of cofactors and their related electron transport proteins, has ensured that preparative biocatalytic hydroxylations are most usefully performed with whole-cell catalysts. The ex-ceptions to this generality, the lipoxygenases and haloperoxidases, will be considered in