Antibody-catalyzed enantioselective Robinson annulation
Antibody-catalyzed enantioselective Robinson annulation
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DOI：
10.1021/ja970944x
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发表时间：
1997-08-27
影响因子：
15
通讯作者：
Barbas, CF
中科院分区：
文献类型：
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作者：
Zhong, GF;Hoffmann, T;Barbas, CF
我们报告的抗体是显着的，因为它催化两个步骤的一个重要的合成转化，罗宾逊环。罗宾逊环化反应在有机合成中起着关键的作用，它完成了一个官能团的净转化。1在大多数情况下，整个环化包括烷基化（或迈克尔加成）步骤，得到B，然后是环化脱水步骤，得到环烯酮B f c。通过罗宾逊环化序列组装的特别公知的合成中间体是Wieland-Miescher（WM）酮6。[2]一般来说，罗宾逊成环反应，特别是WM酮，已经在天然产物，特别是甾族化合物和萜类化合物的合成中无数次使用。例如，最近紫杉醇的全合成从WM酮的（S）-对映体开始。3对于这一点，以及其他应用，4，5的WM酮的对映体纯版本的可用性是非常有帮助的。然而，在实践中，在前手性5环化步骤中的对映体选择性在生成6的过程中大约为70%对映体过量（ee）。分级结晶，伴随着损失，是获得所需的6的（R）-或（S）-对映体或其衍生物的可接受的均匀性所必需的。本文所述研究的目的是探索利用催化抗体实现整个罗宾逊环化序列（a f B f c）和环化脱水步骤（B f c）的可能性。对于合成WM酮的情况，我们探讨了在最后一步中的对映选择是否（参见。5 f 6）可以在催化抗体的治理下实现。
We report an antibody that is remarkable in that it catalyzes both steps of an important synthetic transformation, the Robinson annulation. The Robinson annulation which accomplishes, in net terms, the conversion of a f c occupies a key role in organic synthesis. 1 In most instances, the overall annulation is comprised of an alkylation (or Michael addition) step leading to b followed by a cyclodehydration step to give a cycloalkenone b f c.A particularly well-known synthetic intermediate, which is assembled through a Robinson annulation sequence, is the Wieland-Miescher (WM) ketone 6. 2 The Robinson annulation reaction, in general, and the WM ketone, in particular, have been employed on countless occasions in the synthesis of natural products, notably steroids and terpenoids. 1a-c For instance, a recent total synthesis of taxol started with the (S)-antipode of the WM ketone. 3 For this, as well as other applications, 4, 5 the availability of the enantiopure version of the WM ketone is enormously helpful. In practice, however, the enantioselection in the cyclization step of prochiral 5 en route to 6 is on the order of 70% enantiomeric excess (ee). 2, 6 Fractional crystallization, with attendant losses, is necessary to attain acceptable homogeneity of the desired (R)-or (S)-antipode of 6 or derivatives thereof. The goals of the research described herein were to explore the possibility of utilizing catalytic antibodies to achieve the entire Robinson annulation sequence (a f b f c) and the cyclodehydration step (b f c). For the case of the synthesis of the WM ketone, we explore whether enantioselection in the last step (cf. 5 f 6) could be achieved under governance by the catalytic antibody.