The manzamine alkaloids.
The manzamine alkaloids.
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DOI：
10.1016/s0099-9598(03)60004-0
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发表时间：
2003-01-01
期刊：
影响因子：
--
通讯作者：
Kelly, Michelle
中科院分区：
文献类型：
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作者：
Hu, Jin-Feng;Hamann, Mark T;Kelly, Michelle
从海洋生物中鉴定出的生物碱数量继续以越来越快的速度增长，但很少有（如果有的话）在分子结构上提供可比的复杂性或与曼扎明类一样有希望的生物学意义。曼扎胺是一类独特的含 β-咔啉的生物碱，具有不寻常的多环系统，是从 20 世纪 80 年代末开始从海绵中发现的。比嘉小组分离出的此类生物碱的第一个代表物被鉴定为曼扎明 A (1)(图 1)(1)，其相对构型和绝对构型在当时被认为是前所未有的。盐酸曼扎明 A (1a) 的 X 射线衍射晶体分析表明，除了 β-咔啉取代基外，该分子还包含复杂的 5、6、8 和 13 元环阵列。哌啶和环己烯环系统分别采用椅式和船式构象，而吡咯烷环形成包络结构。 8元Z-烯环的构象为包络船形，镜面穿过C-32和C-28。曼扎胺 A 的两个六元环由八个碳原子链桥接，构成具有四角构象的 13 元大环。连接曼扎胺 A 的 C-12 至 C-19 的六个键形成一个“凸面”和一个贯通双键和 C-36 原子的伪镜面 (1)。近年来，曼扎胺已被视为一组有趣的海洋生物碱，具有非凡的生物活性，因此这些化合物已成为有关其化学和药理学的多项综述的主题 （2-4）。此外，曼扎胺也因其前所未有的生物合成途径引起了人们的极大兴趣。 1992 年，Baldwin 等人(5) 首次提出了一种可能的生物发生途径，涉及曼扎胺 A (1) 和 B (2) 的分子内 Diels-Alder 反应。该生物发生方案表明大环双二氢吡啶可能源自氨、C3 单元和C10 单元。然后，双二氢吡啶可以通过狄尔斯-阿尔德型[4+2]分子内环加成转化为五环中间体，进而通过四环中间体提供曼扎胺A和B。然后，曼扎明 C (3) 可以通过涉及四个单元的简单过程轻松形成相关产品，包括：色氨酸、氨、C3 丙烯醛和 C10 对称二醛（方案 1）(5)。
The number of alkaloids identified from marine organisms continues to grow at an increasing rate, but few, if any, provide comparable sophistication in molecular architecture or as promising a biological significance as the manzamine class. The manzamines are a unique class of β-carboline-containing alkaloids with an unusual polycyclic system identified from marine sponges beginning in the late 1980s. The first representative of this class of alkaloids isolated by Higa’s group was identified as manzamine A (1)(Fig. 1)(1), and the relative, as well as absolute, configuration was considered unprecedented at the time. X-ray diffraction crystallographic analysis of manzamine A hydrochloride (1a), showed that apart from the β-carboline substituent, the molecule comprises a complicated array of 5-, 6-, 8-, and 13-membered rings. The piperidine and cyclohexene ring systems adopt chair and boat conformations, respectively, while the pyrrolidinium ring forms an envelope. The conformation of the 8-membered Z-olefinic ring is in an envelope-boat, with a mirror plane passing through C-32 and C-28. The two, six-membered rings of manzamine A are bridged by a chain of eight carbon atoms constituting a 13-membered macrocycle with a quadrangular conformation. The six bonds joining C-12 to C-19 of manzamine A form a “convex side” and a pseudo mirror plane transfixing the double bond and the C-36 atom (1).In recent years, the manzamines have been regarded as an intriguing group of marine alkaloids with extraordinary biological activity, and as a result these compounds have been the subject of several reviews regarding their chemistry and pharmacology (2–4). In addition, the manzamines have also provoked a great deal of interest in their unprecedented biosynthetic pathway. In 1992 Baldwin et al.(5) first proposed a plausible biogenetic pathway involving an intramolecular Diels-Alder reaction for manzamines A (1) and B (2). This biogenetic scheme suggested that a macrocyclic bisdihydropyridine maybe derived from ammonia, a C3 unit, and a C10 unit. The bisdihydropyridine could then be converted through a Diels-Alder-type [4+ 2] intramolecular cycloaddition into a pentacyclic intermediate, which, in turn, would provide manzamines A and B via a tetracyclic intermediate. Manzamine C (3) could then easily be formed as a related product through a straightforward process involving four units including: tryptophan, ammonia, a C3 acrolein, and a C10 symmetrical dialdehyde (Scheme 1)(5).