Alkaloids structural types

Since the last major review of the biosynthesis of the monoterpenoid indole alkaloids (97), there have been several full and partial 98-104) reviews of various aspects of the work that has been conducted since 1974. Two major developments have dominated the field in this period, namely, the demonstrations that (i) strictosidine (33) is the universal precursor of the monoterpenoid indole alkaloids and (ii) selected cell-free systems of C. roseus have the ability to produce the full range of alkaloid structure types, including the bisindoles. This section traces some aspects of these developments, paying particular attention to work been carried out with C. roseus, and omitting work, important though it may be, on other monoterpenoid indole alkaloid-producing plants, e.g., Rauwolfia, Campto-theca, and Cinchona. 

This is the latest volume in the series "The Alkaloids Chemistry and Biology and covers a group of alkaloids comprising the carbazole nucleus. Single-topic volumes in this series have been rare, and the last one discussed antitumor alkaloids and was published as Volume 25 in 1985. This is the first volume dedicated to a single alkaloid structure type since Volume 8, which dealt with the monoterpene indole alkaloids over 40 years ago. 

Quite the most intriguing new indole alkaloidal structural type to appear this year is that of ervatamine (17b) which occurs, together with 20-epi-ervatamine (17c) and 19,20-dehydroervatamine (17a), in Ervatamia orientalis.26a A description of the degradations (Scheme 5) which led to the structural assignments is included in this sub-section on the basis of a possible biogenetic relationship to alkaloids in this class (see below). 

Following this first section detailing reviews and publications of general interest, the remainder of this chapter is sub-divided according to the different alkaloid structural types. For the order within each sub-group see Ref. la. 

Some of the above considerations led to the proposal which has resulted in this compilation of plant species and the classification according to their contained indole alkaloid structural types. The key to this classification is derived from the recent biosynthetic work of Arigoni (2), Battersby 3, 3a), Leete (4), and Scott (5), and their respective co-workers which, in its infancy when Volume VIII of this series was in publication, now presents conclusive evidence concerning the origin of the complex indole alkaloids in plants 5a). 

In spite of the diverse nature of alkaloid structures, two structural units, i.e. fused pyrrolidine and piperidine rings in different oxidation states, appear as rather common denominators. We therefore chose to give several examples for four types of synthetic reactions which have frequently been used in alkaloid total synthesis and which provide generally useful routes to polycyclic compounds with five- or six-membered rings containing one nitrogen atom. These are ... 

Of the 27 alkaloids isolated from 7. eglandulosa, eight were found to belong to a new structural type, never found before in nature, the tacaman type (105). Tacamine (186, C2lH26N203), the first isolated and most representative al-... 

Aside from yielding the most complex insect alkaloids so far characterized, coccinellid beetles are sources of a wide array of structural types. 

Kinghom, A.D. and Balandrin, M.F. (1984). Quinolizidine alkaloids of the Leguminosae Structural types, analysis, chemotaxonomy and biological activities, in Pelletier, S.W., Ed., Alkaloids chemical and biological perspectives, John Wiley and Sons, New York, pp. 105-148. 

Intrigued by the hypothesis of a dehydrosecodine (120) as a key bioge-netic intermediate in the natural generation of alkaloid structures of both the Aspidosperma (tabersonine, 121) and the Iboga (catharanthine, 21) types (Scheme 33) 108, 109) we developed efficient biomimetic synthe-... 

The natural Aristolochia N-containing substances may be divided into three structural types nitrophenanthrenic acids, phenanthrene lactams, and isoquinoline alkaloids. 

An Entry to Indole Alkaloids of Unusual Structural Type... 

The Aspidosperma alkaloid vincadifformine 1 is reasonably available, and can be readily transformed into the carbinolamine ether 2. Oxidation of 2 with MCPBA followed by methanolysis gives the hemiketal 3, and brief treatment of 3 with a 99 1 v/v mixture of CH2CI2/TFA at room temperature gives a mixture of 4 (42%) and 5 (11%). The yield of 4 is increased to 52%, while almost none of 5 is formed, if the treatment of 3 with acid is allowed to proceed at room temperature for 15 hours. Products 4 and 5 contain the gross skeleton of goniomitine 6, an indole alkaloid of an unusual structural type. 

Diterpenoid Alkaloid Natural Occurrence (N) Derivative (D) Structure Type X-Ray H c... 

The variety of structural types that are encountered in alkaloids belonging to the Amaryllidaceae family can be conveniendy classified, from the point of view of their basic skeleton, along the following lines (see Figure 1) ... 

Extracts of Amaryllidaceae alkaloids have long been used in traditional medicine for the treatment of a variety of illnesses. As early as the fourth century B.C., Hippocrates had reputedly advised the use of preparations of Amaryllidaceae plants to control uterine tumours [157]. More recently, a systematic bioassay of these alkaloids of different structural types has revealed a diversity of interesting biological properties. Thus, (+)-pretazettine (369) [158,159], and ungeremine (182) [160] show anti-leukemic activity. Cytotoxicity was observed for (-)-lycorine (245) [161], (-)-pseudolycorine (574) [162], 6-a-hydroxycrinamine (575) [163],... 

During the last decade, as the number of bisbenzylisoquinoline alkaloids continued to increase rapidly, a systematic classification system became highly desirable, and no doubt many workers were using informal systems. In 1976, a formal line notation was developed that designates the skeleton and location of substituents (337) it is suitable for computer retrieval and has found use in review articles (see Section IX). A more extended system that allows specification of substituents and is adaptable to unusual structural types [e.g., repanduline (Section H,B,7)] has also been described (338). The chirality of asymmetric centers may also be designated (160). 

T. Kametani, The Chemistry of the Isoquinoline Alkaloids, Vol. 2, Chapt. 7. Sendai Institute of Heterocyclic Chemistry, Sendai, 1974. A listing of 95 bisbenzylisoquinoline alkaloids arranged by structural types, with structures, molecular formulas, and references to papers citing physical properties, sources, structure proof, and synthesis. A comprehensive summary with 111 references. 

K. P. Guha, B. Mukhetjee, and R. Mukherjee, J. Nat. Prod. 42, 1 (1979). Bisbenzylsio-quinoline alkaloids. Tabular discussion of 186 alkaloids, arranged by structural type, giving detailed physical data, sources, and synopses of structure proofs. Includes a section on chemical methods of structure proof. Covers literature to 1977 277 references. 

H. Guinaudeau, A. J. Freyer, and M. Shamma, Nat. Prod. Rep. 3, 477 (1986). Spectroscopy of bisbenzylisoquinoline alkaloids. Tabulation and analysis of high resolution NMR spectra of over 100 bisbenzylisoquinoline alkaloids, arranged by structural types 27 references. 

Clivojuline (195) (10) represents an unusual structural type since it lacks the 9,10-aromatic oxygenation pattern, which is ubiquitious among the other lactone alkaloids. The structure of the related alkaloid cliviahaksine (196) was assigned on the basis of spectral comparisons with 195 although its stereochemistry was not specifically indicated (15). Since cliviaaline (197) was isolated in only very small amounts, its structure was deduced principally from its IR spectrum and its mass spectral fragmentation pattern however, the possibility that it was an artifact was not rigorously excluded (14). 

As a result of mass spectral studies of alkaloid extracts of Crinum ornatum, the new alkaloids omazamine, and omazidine were identified, and the tentative structure assignments of 403-405, respectively, were made (42). The stereochemistry depicted is based on the obvious relationship between these alkaloids and pretazettine (395), but no stereochemical details were given in the original report (42). The structures of ungvedine (399) (83) and varadine (402) (54), the latter of which represented a new structural type in the Amaryllidaceae alkaloids, were determined by spectroscopic studies. Further chemical support for the proposed structure of ungvedine (399) was obtained by hydrogenation of O-methyltazettine to give 399 (83). 

---