Aspidosperma-type 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]. 

Aspidosperma alkaloids These alkaloids have an aspidosperma-type nucleus. The a and are the same as in corynanthe type. Catharantine is the P4 from cathenamine (Figure 68). 

During studies on the total synthesis of Aspidosperma type alkaloids, unexpected difficulty was encountered in attempts to reduce the amide carbonyl group of the intermediate 1. Thus, many attempts to reduce 1 with lithium aluminium hydride resulted in reduction of both the amide carbonyl group and the C=C double bond. In an effort to circumvent this problem 1 was reacted with hot phosphorus oxychloride and the intermediate thus obtained treated with sodium borohydride in anhydrous methanol. The product which was isolated, however, was the pentacyclic compound 2, which was obtained in 50% yield. 

Terpenoid Indole Alkaloids.—Current knowledge on the biosynthesis of terpenoid indole alkaloids, with particular emphasis on the very important results obtained with enzyme preparations from tissue cultures of Catharanthus roseus, has been authoritatively reviewed.53 Further work on cell lines of C. roseus that are able to produce Aspidosperma-type alkaloids has been published54 (cf. Vol. 11, p. 19). 

Aspidosperma-type molecules whose structures were derived largely from a detailed physical examination of the bases and their derivatives (principally by mass spectra see Chart III), a technique discussed on a broader basis under Aspidosperma. Similarly, the structures of some of the strychnoid bases were obtained by physical methods. There is no way of knowing which of the alkaloids listed in the table could be identical with either the amorphous bases of Greshoff (10) or the base tartrates and sulfates reported by Australian workers (11). 

Vindoline, an aspidosperma-type alkaloid produced by C. roseus, is a key precursor for vinblastine, an anticancer drug that is the most important pharmaceutical product of C. roseus. Vindoline, like ajmalicine and ajmaline, is produced from degly-cosylated strictosidine. Deglycosylated strictosidine is converted to tabersonine through a series of biochemical steps for which no enzymatic information exists. More details are known about... 

A. scholaris also contains the ring-opened aspidosperma-type alkaloid, leuconolam (172), which is not present in any of the other Asian A. scholaris samples [96], It is perhaps pertinent to note that similar 6,7-seco-angustilobine B-type alkaloids have also been obtained from another Indonesian Alstonia (A. angustiloba [103] although similar compounds were not detected from an examination of the Malaysian samples. 

Tabernaemontana divaricata (double flower variety) provided an unusual minor alkaloid, voaharine (178), whose structure was established by X-ray analysis [137]. Voaharine is exceptional in being in all probability a tryptamine and jccologanine derived alkaloid but possessing a 3-quinolone instead of an indole chromophore. Voaharine is probably derived from voaphylline (180) (which is also present in the plant) via oxidation and rearrangement and represents the first instance of a 3-quinolone-type alkaloid obtained from Tabernaemontana. Besides these, and the known alkaloids N-methylvoaphylline (181), pachysiphine (tabersonine-P-epoxide) and apparicine, as well as two new bisindoles (vide infra), the plant also provided several new alkaloids of the aspidosperma-type including (-)-mehranine (179), voafinine (182), N-methylvoafinine (183), voafinidine (184) and voalenine (185) which were obtained in minute amounts [138-140]. 

The popular garden plant Tabernaemontana divaricata which is extensively grown in gardens in Malaysia as well as in India provided several novel bisindoles, one of which, viz., conophylline (303) has been shown to be a potent inhibitor of ras functions (vide infra). There are two distinct varieties, the single flower variety produces both conophylline (303) and conophyllidine (304) [137,180] while the double flower variety gives in addition, a third dimeric alkaloid, conofoline (305) [ 138] as well as several new aspidosperma-type compounds. 

Researches carried out to the early part of 1966 have been comprehensively reviewed and the present account will set out from that point. In brief, the situation reached at that time was as follows. Despite their bewildering variety, three main groups of alkaloids had been recognised (a) the Corynanthe-Strychnos type, e.g. ajmalicine (1) and akuammicine (2) which possess the non-tryptamine unit (3), (b) the Aspidosperma type, e.g. vindoline (4), in which the non-tryptamine unit appears as (5), and (c) the Iboga type, e.g. catharanthine (6), having still a different arrangement of the non-tryptamine unit (7). 

Rearrangements of Iboga and Aspidosperma Types. It is possible to envisage the biological rearrangements of the monoterpene-tryptamine alkaloid skeleta as proceeding via a common intermediate (132), reversibly derivable, at least on paper (see below) from each of the skeletal types, providing that a structure at the correct oxidation level is chosen. Thus tabersonine (133) (aspidosperma). 

Gabetta (3) has summarized the indole alkaloids isolated between 1968 and mid-1972, and Aliev and Babaev (4) have discussed the physical properties of the many Aspidosperma-type alkaloids isolated from Vinca species. 

Includes alkaloids with one moiety of Pleiocarpa or Aspidosperma type, excepting Vinca alkaloids for which see Chapter 12, Volume VIII and Chapter 5 of this Volume. Some double alkaloids of unknown structure are included. 

Alalakine, the remaining Aspidosperma-type alkaloid to be identified, is new, and exhibits an ultraviolet spectrum similar to that of obscurinervine. Its i.r. spectrum contains a double absorption in the carbonyl region that is reminiscent of the y-lactone absorption of 18-oxoaspidoalbine derivatives, while its mass spectrum contains peaks similar to those derived from the aromatic portion of obscurinervine and the hydroaromatic part of O-methyl-18-oxoaspidoalbine. On the basis of these data, and the 400 MHz n.m.r. spectrum, alalakine is formulated as (190). ... 

C19H26N2, Mr 282.43, mp. 147-149 °C soluble in acetone, chloroform, dilute acids. A monoterpenoid indole alkaloid of the Aspidosperma type, Q. occurs in both enantiomeric forms the (+)-form, (aJu +98° (CHCI3), in leaves and root bark of Pleiocarpa species as well as the bark of Stemmadenia species the (-)-form, [aJi, -100° (CHCI3), in Aspidosperma quebra-cho-blanco and other Aspidosperma species as well as Gonioma, Hunteria, and Rhazya species. 

In contrast to the many Aspidosperma-Aspidosperma type bisindoles found in the leaf extract of the Malaysian T. divaricata vide infra), the stem extract provided only one bisindole, conodusarine (509), which was of the iboga-vobasine type 309). The spectral data indicated that conodusarine (509) is constituted from the union of 3-vobasinyl and 3-oxovoacangine moieties via a 3-11 bond. The presence of the latter alkaloid in the same plant provided additional support for the assignment. 

As a further extension of push-pull dipole cycloaddition chemistry, the Rh (I I)-catalyzed cycHzation/cycloaddition cascade was applied toward the hexacyclic framework of the kopsifoline alkaloids. The kopsifolines 14 are structurally intriguing compounds, related to and possibly derived from an aspidosperma-type alkaloid precursor 12. A possible biogenetic pathway to the kopsifolines from 12 could involve an intramolecular epoxide-ring opening followed by loss of H2O as shown in Scheme 4. The interesting biological activity of these compounds, combined with their... 

The synthetic utility of the Overman pyrrolidine synthesis has been demonstrated in various approaches to a range of alkaloids the Amaryllidaceae alkaloids, Aspidosperma alkaloids, Strychnos alkaloids, and Melodinus alkaloids are several types. 

Most L-tryptophan-derived secondary products still possess the indole ring system of this amino acid. Some compounds, however, are quinoline, pyrrole or benzene derivatives. Additional rings may be present yielding complicated structures, like that of ergoline and / -carboline alkaloids (cf. the formulas of ergotamine, Corynanthe, Strychnos, Iboga and Aspidosperma-type alkaloids). 

Fig. 261. Transformation of ajmalicine to alkaloids with Corynanthe-type, Iboga-type, and Aspidosperma-type skeletons...

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