Serafimov Jörg M, Gillingham Dennis, Kuster Simon, Hilvert Donald
Laboratory of Organic Chemistry, ETH Zurich, CH-8093 Zurich, Switzerland.
J Am Chem Soc. 2008 Jun 25;130(25):7798-9. doi: 10.1021/ja8017994. Epub 2008 May 31.
We find that the putative Diels-Alderase macrophomate synthase (MPS) catalyzes the addition of pyruvate enolate, generated by decarboxylation of oxaloacetate, to a variety of aldehydes. Alkyl, aryl, and heteroaryl aldehydes are accepted as substrates, providing gamma-hydroxy-alpha-ketoacids in 35-95% yield with modest levels of stereochemical control. These aldol products, which are difficult to synthesize by other methods, are formed with efficiency comparable to that of macrophomate. Our results thus provide evidence that a two-step Michael-aldol pathway is a plausible alternative to the postulated [4 + 2] cycloaddition in the MPS-catalyzed addition of pyruvate enolate to 2-pyrones. They are also relevant to understanding the divergent evolution of type II pyruvate aldolases.
我们发现，假定的狄尔斯-阿尔德酶——巨马酚合酶（MPS）催化由草酰乙酸脱羧生成的丙酮酸烯醇化物与多种醛类的加成反应。烷基、芳基和杂芳基醛均可作为底物，以35% - 95%的产率生成γ-羟基-α-酮酸，立体化学控制水平适中。这些通过其他方法难以合成的羟醛产物，其生成效率与巨马酚相当。因此，我们的结果表明，在MPS催化丙酮酸烯醇化物与2-吡喃酮的加成反应中，两步迈克尔-羟醛途径是假定的[4 + 2]环加成反应的一种合理替代途径。它们也有助于理解II型丙酮酸醛缩酶的趋异进化。
