An enzymatic, stereoselective synthesis of (S)-norcoclaurine
An enzymatic, stereoselective synthesis of (S)-norcoclaurine
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DOI：
10.1039/c0gc00036a
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发表时间：
2010-01-01
期刊：
影响因子：
9.8
通讯作者：
Macone, Alberto
中科院分区：
文献类型：
--
作者：
Bonamore, Alessandra;Rovardi, Irene;Macone, Alberto
使用重组 (S)-去甲乌药碱合酶 (NCS)，以廉价的酪氨酸和多巴胺底物为原料，通过一锅两步工艺，开发出一种高效、立体选择性、绿色合成 (S)-去甲乌药碱 (higenamine) 的方法。生物转化的关键步骤包括通过化学计量的次氯酸钠对酪氨酸进行氧化脱羧，以生成 4-羟基苯乙醛，然后在抗坏血酸存在下添加酶和多巴胺底物，抗坏血酸是避免儿茶酚部分氧化的必要成分。通过吸附到分散在反应混合物中的活性炭上来实现从水溶液中定量萃取产物。优化的工艺提供了对映体纯的 (S)-去甲乌云碱 (93%)，产率高于 80%，并且可以很好地回收酶以进行再循环。由此开发的工艺代表了绿色Pictet-Spengler合成的第一个例子，这可能为苄基异喹啉生物碱合成的新策略铺平道路。
An efficient, stereoselective, green synthesis of (S)-norcoclaurine (higenamine) has been developed using the recombinant (S)-norcoclaurine synthase (NCS) enzyme, starting from the cheap tyrosine and dopamine substrates in a one-pot, two step process. Key steps in the biotransformation consist of the oxidative decarboxylation of tyrosine by stoichiometric amounts of sodium hypochlorite in order to generate 4-hydroxyphenylacetadehyde, followed by the addition of enzyme and dopamine substrate in the presence of ascorbate, a necessary ingredient in order to avoid oxidation of the catechol moiety. Quantitative extraction of the product from an aqueous solution was achieved by adsorption onto active charcoal dispersed in the reaction mixture. The optimized process afforded enantiomerically pure (S)-norcoclaurine (93%) in a yield higher than 80% and allowed good recovery of the enzyme for recycling. The process thus developed represents the first example of a green Pictet-Spengler synthesis, which may pave the way to novel strategies in benzylisoquinoline alkaloid synthesis.