Synthesis, biosynthesis, and absolute configuration of vioxanthin
Synthesis, biosynthesis, and absolute configuration of vioxanthin
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DOI：
10.1002/anie.200701014
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发表时间：
2007-01-01
影响因子：
16.6
通讯作者：
Mueller, Michael
中科院分区：
文献类型：
--
作者：
Bode, Silke E.;Drochner, Daniel;Mueller, Michael
联芳基轴是在多种生物活性天然产物中发现的结构元件。[1]此外，联芳基化合物在有机合成中也是重要的物质，例如作为对映选择性合成的多功能助剂和不对称催化中的配体。二元化合物天然产物的生物合成是通过氧化苯酚偶联进行的，正如植物、细菌和真菌的几种二元化合物次级代谢产物所证明的那样。[1，2]然而，通过氧化苯酚偶联的（邻）二聚步骤的确切机理仍然不清楚。[3]在非酶促联芳基合成中，与所描述的生物合成过程相比的区域选择性和立体选择性的控制尚未实现。[4，5]因此，我们的目标是鉴定参与区域和立体选择性分子间氧化苯酚偶联的生物催化剂。在此，氧化酚偶联在紫黄质的生物合成进行了探讨，以了解区域和立体选择性是如何控制的性质。因此，对紫黄质（1）及其异构体的绝对构型的阐明以及合成是必不可少的。双芳基二氢萘并吡喃酮紫黄质（1）由Blank埃塔尔首次分离得到。紫色发癣菌的病原体[6]Zeeck埃塔尔分离自黄绿青霉（Penicillium citreoviride）的1与单体化合物（R）-半维黄质（（R）-2）。[7]他们通过比较2的圆二色性（CD）光谱和（R）-melllein的圆二色性光谱，确定了2的绝对构型为R。[7]1的圆二色光谱显示正手性，因此推测1的绝对构型为P，R，R。[8]然而，仅通过旋光方法的这种测定有些模糊（见下文）。
The biaryl axis is a structural element found in a broad variety of bioactive natural products.[1] Moreover, biaryl compounds are important substances in organic synthesis, for example, as versatile auxiliaries for enantioselective synthesis and as ligands in asymmetric catalysis. The biosynthesis of biarylic natural products proceeds through an oxidative phenol coupling, as has been proven for several biarylic secondary metabolites from plants, bacteria, and fungi.[1, 2] However, the exact mechanism of the (dehydro) dimerization step through oxidative phenol coupling is still unclear.[3] In nonenzymatic biaryl synthesis, a control of regio-and stereoselectivity comparable with that of the described biosynthetic process has not been achieved yet.[4, 5] Thus, our goal is to identify biocatalysts involved in the regio-and stereoselective intermolecular oxidative phenol coupling. Herein, oxidative phenol coupling in the biosynthesis of vioxanthin is explored to understand how regio-and stereoselectivity is controlled in nature. For this purpose, the elucidation of the absolute configuration as well as the synthesis of vioxanthin (1) and its isomers are essential. The biarylic dihydronaphthopyranone vioxanthin (1) was first isolated by Blank etal. from the pathogenic fungus Trichophyton violaceum.[6] Zeeck etal. isolated 1 from Penicillium citreoviride together with the monomeric compound (R)-semivioxanthin ((R)-2).[7] They determined the absolute configuration of 2 as R by comparison of its circular dichroism (CD) spectrum with that of (R)-mellein.[7] The CD spectrum of 1 shows positive chirality, thus the absolute configuration of 1 was supposed to be P, R, R.[8] However, this determination solely by chiroptical methods was somewhat ambiguous (see below).