Stereospecific synthesis of 23-hydroxyundecylprodiginines and analogues and conversion to antimalarial premarineosins via a Rieske oxygenase catalyzed bicyclization.
Stereospecific synthesis of 23-hydroxyundecylprodiginines and analogues and conversion to antimalarial premarineosins via a Rieske oxygenase catalyzed bicyclization.
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DOI：
10.1021/jo5023553
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发表时间：
2014-12-05
期刊：
影响因子：
--
通讯作者：
Reynolds KA
中科院分区：
文献类型：
--
作者：
Kancharla P;Lu W;Salem SM;Kelly JX;Reynolds KA
已经建立了(S)-和(R)-23-羟基十一烷基prodiginine (（23S)-2和(23R)-2）、23-酮癸基prodiginine(3)和氘标记的23-羟基十一烷基prodiginine （[23-d]-2）的简便高效的合成路线。我们利用MarG异源表达系统，证明了一种新的Rieske加氧酶MarG催化(23S)-2立体选择性双环化到海洋皂苷a(4)，这是海洋皂苷生物合成的关键步骤。合成了多种a - c环功能化的prodiginine 32-41，研究了MarG的底物混杂性。这两个类似物32和33对恶性疟原虫（CQS-D6、CQR-Dd2和7G8）和肝细胞HepG2癌细胞的抗疟和细胞毒活性分别强于海洋皂苷中间体2。将34-36投喂给表达marG的委内瑞拉链霉菌可产生新型海洋皂苷，为通过组合合成/生物合成方法生产海洋皂苷类似物铺平了道路。本研究提出了由Rieske加氧酶介导的氧化双环化的第一个例子。
Facile and highly efficient synthetic routes for the synthesis of (S)- and (R)-23-hydroxyundecylprodiginines ((23S)-2, and (23R)-2), 23-ketoundecylprodiginine (3), and deuterium-labeled 23-hydroxyundecylprodiginine ([23-d]-2) have been developed. We demonstrated a novel Rieske oxygenase MarG catalyzed stereoselective bicyclization of (23S)-2 to premarineosin A (4), a key step in the tailoring process of the biosynthesis of marineosins, using a marG heterologous expression system. The synthesis of various A–C-ring functionalized prodiginines 32–41 was achieved to investigate the substrate promiscuity of MarG. The two analogues 32 and 33 exhibit antimalarial and cytotoxic activities stronger than those of the marineosin intermediate 2, against Plasmodium falciparum strains (CQS-D6, CQR-Dd2, and 7G8) and hepatocellular HepG2 cancer cell line, respectively. Feeding of 34–36 to Streptomyces venezuelae expressing marG led to production of novel premarineosins, paving a way for the production of marineosin analogues via a combinatorial synthetic/biosynthetic approach. This study presents the first example of oxidative bicyclization mediated by a Rieske oxygenase.
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DOI：
10.4269/ajtmh.1976.25.26
发表时间：
1976-01-01
影响因子：
3.3
作者：
DAVIDSON, DE;JOHNSEN, DO;KINNAMON, KE
通讯作者：
KINNAMON, KE
影响因子：
3.6
作者：
BOGER, DL;PATEL, M
通讯作者：
PATEL, M
影响因子：
3.6
作者：
GREENHOUSE, R;RAMIREZ, C;MUCHOWSKI, JM
通讯作者：
MUCHOWSKI, JM
影响因子：
2.1
作者：
Kancharla, Papireddy;Reynolds, Kevin A.
通讯作者：
Reynolds, Kevin A.
DOI：
10.1073/pnas.0337542100
发表时间：
2003-02-18
影响因子：
11.1
作者：
Gust, B;Challis, GL;Chater, KF
通讯作者：
Chater, KF