Total synthesis of the aristolochic acids, their major metabolites, and related compounds.
Total synthesis of the aristolochic acids, their major metabolites, and related compounds.
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阿里斯洛胆酸，主要代谢产物及相关化合物的总合成。
DOI：
10.1021/tx500122x
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发表时间：
2014-07-21
影响因子：
4.1
通讯作者：
Johnson, Francis
中科院分区：
文献类型：
--
作者：
Attaluri, Sivaprasad;Iden, Charles R.;Bonala, Radha R.;Johnson, Francis
马兜铃属植物自希波克拉底时代以来就被推荐用于治疗各种人类疾病。然而，许多物种产生高毒性马兜铃酸（AAs），这是肾毒性和致癌性。为了进行广泛的生物学研究，主要基于Suzuki-Miyaura偶联反应设计了一种合成AA及其主要代谢物的通用方法。成功的关键在于制备共同的A环前体，即2-硝基甲基-3-碘-4，5-亚甲二氧基苄醇的四氢吡喃基醚（27），其通过醛肟前体26的氧化以优异的产率产生。27与各种苯甲醛2-硼酸酯的Suzuki-Miyaura偶联伴随着羟醛缩合/消除反应，直接得到所需的菲中间体。苯甲醇脱保护，然后进行两个连续的氧化步骤，得到所需的菲硝基羧酸。这种方法被用来合成AAs I-IV和其他几种相关的化合物，包括AA I和AA II轴承的氨基丙氧基基团的位置-6，这是需要进一步转化为荧光生物探针。Suzuki-Miyaura偶联反应进一步成功应用于AA I和AA II的N-羟基马兜铃内酰胺的合成，然后允许合成推定的、但迄今为止难以捉摸的N-乙酰氧基-和N-磺酰氧基-马兜铃内酰胺代谢物。
Plants from the Aristolochia genus have been recommended for the treatment of a variety of human ailments since the time of Hippocrates. However, many species produce the highly toxic aristolochic acids (AAs), which are both nephrotoxic and carcinogenic. For the purposes of extensive biological studies, a versatile approach to the synthesis of the AAs and their major metabolites was devised based primarily on a Suzuki–Miyaura coupling reaction. The key to success lies in the preparation of a common ring-A precursor, namely, the tetrahydropyranyl ether of 2-nitromethyl-3-iodo-4,5-methylendioxybenzyl alcohol (27), which was generated in excellent yield by oxidation of the aldoxime precursor 26. Suzuki–Miyaura coupling of 27 with a variety of benzaldehyde 2-boronates was accompanied by an aldol condensation/elimination reaction to give the desired phenanthrene intermediate directly. Deprotection of the benzyl alcohol followed by two sequential oxidation steps gave the desired phenanthrene nitrocarboxylic acids. This approach was used to synthesize AAs I–IV and several other related compounds, including AA I and AA II bearing an aminopropyloxy group at position-6, which were required for further conversion to fluorescent biological probes. Further successful application of the Suzuki–Miyaura coupling reaction to the synthesis of the N-hydroxyaristolactams of AA I and AA II then allowed the synthesis of the putative, but until now elusive, N-acetoxy- and N-sulfonyloxy-aristolactam metabolites.
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影响因子：
6.1
作者：
Cosyns, JP;Goebbels, RM;Bernard, AM
通讯作者：
Bernard, AM
影响因子：
15
作者：
Jiang, X;García-Fortanet, J;De Brabander, JK
通讯作者：
De Brabander, JK
影响因子：
5.2
作者：
Kim, Joa Kyum;Kim, Young Ha;Heo, Jung-Nyoung
通讯作者：
Heo, Jung-Nyoung
影响因子：
13.2
作者：
Cosyns, JP;Jadoul, M;de Strihou, CV
通讯作者：
de Strihou, CV
影响因子：
1.8
作者：
ESTEVEZ, JC;ESTEVEZ, RJ;CASTEDO, L
通讯作者：
CASTEDO, L