Direct amino acid catalyzed asymmetric synthesis of polyketide sugars
Direct amino acid catalyzed asymmetric synthesis of polyketide sugars
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DOI：
10.1002/anie.200461400
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发表时间：
2005-01-01
影响因子：
16.6
通讯作者：
Córdova, A
中科院分区：
文献类型：
--
作者：
Casas, J;Engqvist, M;Córdova, A
氨基酸与醛和酮形成亲核烯胺的能力已被用于开发与亲电氧化剂的不对称α-氧化反应。单重态分子氧首次不对称掺入到醛和酮中，并以良好的产率和ee分离出相应的二醇。环酮与亚碘酰苯和N-磺酰氧氮丙啶的有机催化α-氧化也是可能的，并且在还原产物二醇后以通常低的产率和低至良好的ee's提供。氨基酸也被证明可以通过连续的羟醛缩合反应催化碳水化合物的形成。例如，脯氨酸和羟基脯氨酸介导高度选择性的α-苄氧基乙醛三聚成阿洛糖，其在> 99%ee中获得。该反应的非线性效应研究揭示了迄今为止在脯氨酸催化反应中观察到的最大永久非线性效应。此外，聚酮化合物也组装在一个类似的方式由氨基酸催化的一锅反应，是成功的三聚丙醛，但顺序交叉羟醛缩合反应遭受较低的选择性。这个问题是克服了两步合成的发展，使形成一系列的聚酮化合物具有优异的选择性，从各种醛。该方法通过报道的最短路线和与大多数多步合成相当的产物产率来合成聚酮化合物。所有聚酮化合物均以单一非对映异构体形式分离，ee> 99%。基于观察到的氨基酸催化作用，氨基酸被认为参与了四糖和己糖的益生元形成。
The ability of amino acids to form nucleophilic enamines with aldehydes and ketones has been used in the development of asymmetric α-oxidation reactions with electrophilic oxidizing agents. Singlet molecular oxygen has for the first time been asymmetrically incorporated into aldehydes and ketones, and the products were isolated as their corresponding diols in good yields and ee’s. Organocatalytic α-oxidations of cyclic ketones with iodosobenzene and N-sulfonyloxaziridine were also possible and furnished after reduction the product diols in generally low yields and in low to good ee’s. Amino acids have also been shown to catalyze the formation of carbohydrates by sequential aldol reactions. For example, proline and hydroxy proline mediate a highly selective trimerisation of α-benzyloxyacetaldehyde into allose, which was obtained in> 99% ee. Non linear effect studies of this reaction revealed the largest permanent nonlinear effect observed in a proline-catalyzed reaction to date. Moreover, polyketides were also assembled in a similar fashion by an amino acid-catalyzed one-pot reaction, and was successful for the trimerisation of propionaldehyde, however the sequential cross aldol reactions suffered from lower selectivities. This problem was overcome by the development of a two-step synthesis that enabled the formation of a range of polyketides with excellent selectivities from a variety of aldehydes. The method furnishes the polyketides via the shortest route reported and in comparable product yields to most multi-step synthesis. All polyketides were isolated as single diastereomers with> 99% ee. Based on the observed amino acid-catalysis, amino acids are thought to have taken part in the prebiotic formation of tetroses and hexoses.