Parallel and four-step synthesis of natural-product-inspired scaffolds through modular assembly and divergent cyclization.
Parallel and four-step synthesis of natural-product-inspired scaffolds through modular assembly and divergent cyclization.
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DOI：
10.3762/bjoc.8.105
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发表时间：
2012
影响因子：
2.7
通讯作者：
Omura S
中科院分区：
文献类型：
--
作者：
Oguri H;Mizoguchi H;Oikawa H;Ishiyama A;Iwatsuki M;Otoguro K;Omura S
通过模拟通用的生物合成策略，采用模块化组装和发散环化，我们已经开发了一个四步合成过程，以产生一系列天然产物启发的支架。通过Ugi缩合、N-乙酰乙酰化和重氮转移，将结构单元模块化组装到具有羧酸基团的基于哌啶的歧管6上，得到环化前体。铑催化的串联环化和发散环加成反应通过适当选择安装在模块3和4处的亲偶极试剂产生四环和六环支架。成功地应用了带有氨基的不同的基于哌啶的歧管15，以证明用于在融合支架中产生结构多样性的统一四步法的灵活性和范围。还进行了体外抗锥虫活性的评价和初步的结构-活性关系（SAR）研究。
By emulating the universal biosynthetic strategy, which employs modular assembly and divergent cyclizations, we have developed a four-step synthetic process to yield a collection of natural-product-inspired scaffolds. Modular assembly of building blocks onto a piperidine-based manifold 6, having a carboxylic acid group, was achieved through Ugi condensation, N-acetoacetylation and diazotransfer, leading to cyclization precursors. The rhodium-catalyzed tandem cyclization and divergent cycloaddition gave rise to tetracyclic and hexacyclic scaffolds by the appropriate choice of dipolarophiles installed at modules 3 and 4. A different piperidine-based manifold 15 bearing an amino group was successfully applied to demonstrate the flexibility and scope of the unified four-step process for the generation of structural diversity in the fused scaffolds. Evaluation of in vitro antitrypanosomal activities of the collections and preliminary structure–activity relationship (SAR) studies were also undertaken.
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影响因子：
5.2
作者：
Bauer RA;DiBlasi CM;Tan DS
通讯作者：
Tan DS
影响因子：
7.8
作者：
Bauer, Renato A.;Wurst, Jacqueline M.;Tan, Derek S.
通讯作者：
Tan, Derek S.
影响因子：
3.8
作者：
Otoguro, Kazuhiko;Iwatsuki, Masato;Yamada, Haruki
通讯作者：
Yamada, Haruki
影响因子：
3.3
作者：
Iwatsuki, Masato;Kinoshita, Yuta;Omura, Satoshi
通讯作者：
Omura, Satoshi
影响因子：
15
作者：
Marcaurelle, Lisa A.;Comer, Eamon;Dandapani, Sivaraman;Duvall, Jeremy R.;Gerard, Baudouin;Kesavan, Sarathy;Lee, Maurice D.;Liu, Haibo;Lowe, Jason T.;Marie, Jean-Charles;Mulrooney, Carol A.;Pandya, Bhaumik A.;Rowley, Ann;Ryba, Troy D.;Suh, Byung-Chul;Wei, Jingqiang;Young, Damian W.;Akella, Lakshmi B.;Ross, Nathan T.;Zhang, Yan-Ling;Fass, Daniel M.;Reis, Surya A.;Zhao, Wen-Ning;Haggarty, Stephen J.;Palmer, Michelle;Foley, Michael A.
通讯作者：
Foley, Michael A.