General synthesis route to benanomicin-pradimicin antibiotics
General synthesis route to benanomicin-pradimicin antibiotics
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DOI：
10.1002/chem.200700863
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发表时间：
2007-01-01
影响因子：
4.3
通讯作者：
Suzuki, Keisuke
中科院分区：
文献类型：
--
作者：
Tamiya, Minoru;Ohmori, Ken;Suzuki, Keisuke
本文介绍了一种区域选择性和立体选择性地全合成拜诺霉素-普拉米星抗生素（BpAs）的方法。糖苷配基的构建是通过以下方式实现的：1）通过使用（R）-缬氨醇作为手性亲核试剂使联芳基内酯非对映选择性开环; 2）在BF 3中心点OEt 2和质子源存在下，通过使用SMI 2使醛缩醛进行立体控制的半频哪醇环化，得到ABCD四环单保护的二醇。该策略使我们能够控制B环中的两个立体位点（C-5和C-6）和碳水化合物部分的区域选择性引入。ne ABCD四环素可以作为一个理想的平台，为不同的访问各种BpAs。在ABCD四环素上引入一个氨基酸（D-丙氨酸）。通过Cp 2 HfCl 2和AgOTf（1：2比率）的组合促进糖基化。构建E环，然后脱保护完成了苯那霉素A（2a）、苯那霉素B（2 B）和普拉米星A（1a）的首次全合成。该路线是灵活的，足以允许其他同源物的合成不同的氨基酸和碳水化合物部分。
A general approach to the regio- and stereoselective total synthesis of the beiianomicin-pradimicin antibiotics (BpAs) is described. Construction of the aglycon has been achieved by 1) the diastereoselective ring-opening of a biaryl lactone by using (R)-valinol as a chiral nucleophile and 2) the stereocontrolled semi-pinacol cyclization of the aldehyde acetal by using SMI2 in the presence of BF3 center dot OEt2 and a proton source to afford the ABCD tetracyclic monoprotected diol. This strategy enabled us to control the two stereogenic sites in the B ring (C-5 and C-6) and the regioselective introduction of the carbohydrate moiety. ne ABCD tetracycle could serve as an ideal platform for the divergent access to various BpAs. ne amino acid (D-alanine) was introduced onto the ABCD tetracycle. Glycosylation was promoted by the combination of Cp2HfCl2 and AgOTf (1:2 ratio). Construction of the E ring followed by deprotection completed the first total synthesis of benanomicin A (2a), benanomicin B (2b), and pradimicin A (1a). The route is flexible enough to allow the synthesis of other congeners differing in their amino acid and carbohydrate moieties.