Gribble Gordon W
Department of Chemistry, Dartmouth College, Hanover, New Hampshire, USA.
Alkaloids Chem Biol. 2012;71:1-165. doi: 10.1016/b978-0-12-398282-7.00001-1.
Once considered to be isolation artifacts or chemical "mistakes" of nature, the number of naturally occurring organohalogen compounds has grown from a dozen in 1954 to >5000 today. Of these, at least 25% are halogenated alkaloids. This is not surprising since nitrogen-containing pyrroles, indoles, carbolines, tryptamines, tyrosines, and tyramines are excellent platforms for biohalogenation, particularly in the marine environment where both chloride and bromide are plentiful for biooxidation and subsequent incorporation into these electron-rich substrates. This review presents the occurrence of all halogenated alkaloids, with the exception of marine bromotyrosines where coverage begins where it left off in volume 61 of The Alkaloids. Whereas the biological activity of these extraordinary compounds is briefly cited for some examples, a future volume of The Alkaloids will present full coverage of this topic and will also include selected syntheses of halogenated alkaloids. Natural organohalogens of all types, especially marine and terrestrial halogenated alkaloids, comprise a rapidly expanding class of natural products, in many cases expressing powerful biological activity. This enormous proliferation has several origins: (1) a revitalization of natural product research in a search for new drugs, (2) improved compound characterization methods (multidimensional NMR, high-resolution mass spectrometry), (3) specific enzyme-based and other biological assays, (4) sophisticated collection methods (SCUBA and remote submersibles for deep ocean marine collections), (5) new separation and purification techniques (HPLC and countercurrent separation), (6) a greater appreciation of traditional folk medicine and ethobotany, and (7) marine bacteria and fungi as novel sources of natural products. Halogenated alkaloids are truly omnipresent in the environment. Indeed, one compound, Q1 (234), is ubiquitous in the marine food web and is found in the Inuit from their diet of whale blubber. Given the fact that of the 500,000 estimated marine organisms--which are the source of most halogenated alkaloids--only a small percentage have been investigated for their chemical content, it is certain that myriad new halogenated alkaloids are awaiting discovery. For example, it is estimated that nearly 4000 species of bryozoans have not been examined for their chemical content. The few species that have been studied contain some extraordinary halogenated alkaloids, such as hinckdentine A (610) and the chartellines (611-613). Of the estimated 1.5 million species of fungi, secondary metabolites have been characterized from only 5000 species. The future seems bright for the collector of halogenated alkaloids!
天然有机卤素化合物曾被认为是分离产物或自然界的化学“错误”，其数量已从1954年的十几种增长到如今的5000多种。其中，至少25%是卤代生物碱。这并不奇怪，因为含氮的吡咯、吲哚、咔啉、色胺、酪氨酸和酪胺是生物卤化的优良平台，特别是在海洋环境中，氯化物和溴化物都很丰富，可用于生物氧化并随后结合到这些富电子底物中。本综述介绍了所有卤代生物碱的存在情况，但海洋溴酪氨酸除外，其内容在《生物碱》第61卷中有介绍。虽然简要列举了一些此类特殊化合物的生物活性，但《生物碱》的后续卷将全面涵盖该主题，还将包括卤代生物碱的部分合成方法。所有类型的天然有机卤素，尤其是海洋和陆地卤代生物碱，构成了一类迅速扩展的天然产物，在许多情况下都具有强大的生物活性。这种大量增加有几个原因：（1）天然产物研究为寻找新药而复兴；（2）化合物表征方法得到改进（多维核磁共振、高分辨率质谱）；（3）基于特定酶和其他生物测定方法；（4）先进的采集方法（用于深海海洋采集的水肺潜水和遥控潜水器）；（5）新的分离和纯化技术（高效液相色谱和逆流分离）；（6）对传统民间医学和民族植物学有了更深入的认识；（7）海洋细菌和真菌作为天然产物的新来源。卤代生物碱在环境中确实无处不在。事实上，一种化合物Q1（234）在海洋食物网中普遍存在，因因纽特人食用鲸脂而在他们体内被发现。鉴于估计有50万种海洋生物——大多数卤代生物碱的来源——中只有一小部分的化学含量得到了研究，肯定还有无数新的卤代生物碱有待发现。例如，据估计，近4000种苔藓虫尚未对其化学含量进行检测。少数已被研究的物种含有一些特殊的卤代生物碱，如欣克登汀A（610）和查泰林类化合物（611 - 613）。在估计的150万种真菌中，只有5000种的次生代谢产物得到了表征。对于卤代生物碱的采集者来说，未来似乎一片光明！
