Of indole alkaloids

Tabersonine (108), clearly a reduced and simplified version of the second-half of the alkaloids 22, was originally isolated inoxsi Pimsonia tabemaemontane V. and is considered to be a simplified parent of a rather more elaborate subgroup of indole alkaloids. 

It is not proposed to discuss these topics, which have been adequately reviewed elsewhere, but to focus attention on general aspects of carboline chemistry, including relevant findings which emerged incidentally in the course of degradative and synthetic work in the field of indole alkaloid chemistry. The only published review on the carbolines emphasizes aspects of the work carried out prior to 1950. 

Further elaboration of tetracycle 159c resulted in the syntheses of the racemate of indole alkaloids of the ajmalicine (61JA2594), tetrahydroalstunine (56JOC1315, 71JA5907), and akuammigine type (ajmalicinoid alkaloids). Similarly, 159d can be converted into yohimboid alkaloids (79JA5370). 

Conformational study of geissoschizine isomers and their model compounds (geissoschizine is the indolo[2,3-fl]quinolizidine derivative considered to be an important participant of indole alkaloids biogenesis) 99H(51)649. 

The nonaromatic lactones from cis-13, and trcyclohexaneacetic acid14 were important intermediates in the synthesis of indole alkaloids. 

Due to the prevalence and diversity of indole alkaloids and the limitations of space, no attempt will be made to describe all of the synthetic efforts in this area. However, noteworthy synthetic achievements include a synthesis of gelsemine <96JA7426>, (+)-duocarmycin by... 

Scott, A.I. "Biosynthesis of Indole Alkaloids", in MTP Inter. Rev. Sci., Org. Chem. Series I Alkaloids 1973, 105-lUl. Eds Wiesner, K. University Park Press. 

Hartman RE et al. (1964) Microbial hydroxylation of indole alkaloids. Appl Microbiol 12 138-140... 

A fourfold anionic domino process consistingofadominoMichael/aldol/Michael/ aldol process was used by Koo and coworkers for the synthesis of bicyclo[3.3.1]non-anes. They employed 2 equiv. of inexpensive ethyl acetoacetate and 1 equiv. of a simple a, 3-unsaturated aldehyde [290]. Differently substituted dihydroquinolines were assembled in a Michael/aldol/elimination/Friedel-Crafts-type alkylation protocol by the Wessel group [291]. An impressive approach in this field, namely the construction of the indole moiety 2-557, which represents the middle core of the man-zamines, has been published by Marko and coworkers [292]. Manzamine A (2-555) and B (2-556) are members of this unique family of indole alkaloids which were isolated from sponges of the genus Haliclona and Pelina (Scheme 2.126) [293]. 

Scheme 2.126. Manzamine A (2-555) and B (2-556) - Members of a unique family of indole alkaloids.

The sequence could even be prolonged by including a Pummerer reaction. Thus, treatment of 4-103 with trifluoroacetic acid (TFA) gave the furan 4-104, which underwent a cycloaddition to furnish 4-105 the erythryna skeleton 4-109 was obtained after subsequent addition of a Lewis acid such as BF3- Et20 (Scheme 4.23) [33]. It can be assumed that 4-106, 4-107 and 4-108 act as intermediates. In a more recent example, these authors also used the procedure for the synthesis of indole alkaloids of the Aspidosperma type [34]. 

Delorenzi JC, Attias M, Gattass CR, Andrade M, Rezende C, Pinto AC, Henriques AT, Bou-Habib DC and Saraiva EM. 2001. Antileishmanial activity of indole alkaloid from Peschiera australis. Antimicrob Agents Chemother 45(5) 1349-1354. 

SMITH, G.N., Strictosidine A key intermediate in the biogenesis of indole alkaloids, Chem. Commun. 1968, 912-914. 

Other reviews related to this contribution should also be mentioned, in addition to the chapters of this series, which we shall recall later. Some of these deal in general with the problem of classification of indole alkaloids and with chemo-taxonomic investigation (7-5). The chemistry of indole alkaloids is included in the Royal Society of Chemistry s Specialist Periodical Reports and has been extensively reviewed in a one-volume survey edited by J. E. Saxton (6), presenting a reasonably complete, although not exhaustive, picture of the state of the art. Other books on indole alkaloid chemistry treating this area cursorily should also be mentioned (7, 8). Recently, the genus Tabernaemontana was excellently reviewed, particularly with respect to taxonomy, phytochemistry, ethnobotany, and pharmacology (9). 

Fig. 1. Classification of indole alkaloids isolated from Tabernaemontana plants.

Atta-ur-Rahman and A. Basha, Biosynthesis of Indole Alkaloids. Oxford Univ. Press (Clarendon), London, 1983. 

B. Gabetta and G. Mustich, Spectral Data of Indole Alkaloids. Invemi della Beffa, Milan, 1975. 

During the past two decades a great number of papers have been published on the isolation, structure elucidation, synthesis and transformation, biogenesis, chemotaxonomy, and pharmacology of indole alkaloids. In this chapter we summarize the new results that appeared from 1968 to mid 1984 for the cory-nantheine-yohimbine group of monoterpene indole alkaloids with greater emphasis on their chemistry, excluding the related oxindoles and heteroyohimbines. 

Two important books on the biogenesis of indole alkaloids have been published (5, 6), therefore we do not intend to cover the literature of the biogenesis of corynantheine- and yohimbine-type alkaloids. Our chapter begins with the structure elucidation of the alkaloids isolated during the past two decades and proceeds with the synthesis, transformation, as well as spectroscopy of the alkaloids in question. 

The conversion of indole alkaloids to oxindole derivatives has been studied extensively. Since this review does not deal with the literature of oxindole alkaloids, only the most important transformations of the alkaloids having indo-loquinolizine as well as yohimbane skeletons are to be mentioned. 

A simple method was developed for the cleavage of the C-2—C-3 bond of indole alkaloids by the use of formic acid-formamide as reagent. Thus 2,3-seco derivatives of yohimbine (74), hirsutine (58), and reserpine (109) were prepared... 

Considerable success has been achieved in isolating plant tissue culture enzymes responsible for specific steps in the biosynthesis of a range of indole alkaloids (187-191). While the subject of biosynthesis is beyond the scope of this review, the value of such enzymes in catalyzing biotransformation reactions... 

Indole derivatives are widespread natural compounds, and mass spectrometry of indole derivates, [225,226] especially of indole alkaloids, has been a topic of interest ever since. [227-229]... 

McClean S, Robinson RC, Shaw C, Smyth WR 2002. Characterization and determination of indole alkaloids in frog-skin secretions by electrospray ionization trap mass spectrometry. Rapid Commun Mass Spectrom 16 346. 

---