Biosynthesis aspidosperma alkaloids

It is suggested in conclusion that (99) occupies a crucial position at the branchpoint in the biosynthesis of Corynanthe, Iboga, and Aspidosperma alkaloids.30... 

For (essentially) the first time recently, strains of C. roseus cultures have been obtained which will synthesize Strychnos, Iboga, and Aspidosperma alkaloids.34 This opens up the exciting possibility of studying the biosynthesis of those alkaloids lying beyond the Corynanthe type, such as (102), by using enzyme preparations from tissue cultures, which have proved so powerful for the early stages of biosynthesis (see above). 

An ingenious solution to this problem has been suggested which involves inversion at C-3, C-7, and C-15 via dihydropyridine intermediates (Scheme 8) and is similar to that proposed to account for the biosynthesis of antipodal pentacyclic Aspidosperma alkaloids. The feasibility of such a mechanism chemically has been demonstrated with the thermal transformation of (107 20a-H) into (108 20-aH). 

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). 

The versatility of strictosidine as a central intermediate for the biosynthesis of a variety of alkaloids is based on the highly reactive dialdehyde produced by the action of strictosidine p-D-glucosidase. This reactive intermediate is converted by uncharacterized enzymes into the major corynanthe, iboga, and aspidosperma skeletons that are elaborated into die several hundred alkaloids found in Catharanthns roseus. Since the biosynthesis of strictosidine appears to occur within plant vacuoles, there has been much speculation, but little is known, about the factors that regulate the accumulation of strictosidine within the vacuole, or which trigger its mobilization for further elaboration. It is well known that glycosides of different natural product classes are located within plant vacuoles. 

Another all-carbon Diels-Alder reaction is proposed for the biosynthesis of the indole alkaloids tabersonine 1-6 and catharanthine 1-7 of the Aspidosperma and Iboga family [28-31]. The compounds are formed via strictosidine 1-3, the first nitrogen-containing precursor of the monoterpenoid indole alkaloids, and stemmadenine 1-4, which is cleaved to give the proposed intermediate dehy-drosecodine 1-5 with an acrylate and a 1,3-butadiene moiety (Scheme 1-1). 

Since oxidized derivatives of secodine appear to be involved as late intermediates in the biosynthesis of the aspidospermidine and pseudoas-pidospermidine alkaloids, it is logical to begin with those secodine derivatives that have been found to occur naturally. Tetrahydrosecodine (1) occurs in the root bark of Aspidosperma marcgravianum Woodson (5) and has been detected in cell-suspension cultures of Rhazya stricta Decaisne (6) its demethoxycarbonyl derivative (2) also occurs in A. marcgravianum (5), and in Haplophyton crooksii L. Benson (7,8) and the roots of R. stricta (9). The two isomeric carbonyl derivatives, 2-ethyl-3-[2-(3-acetyl-V-piperidino)ethyl]indole (3) and crooksidine (4), occur, respectively, in A. marcgravianum (5) and H. crooksii (7,8). 

Eburnamine-Vincamine Alkaloids.—So far most of the effort on indole alkaloid biosynthesis has been concentrated on the Corynanthe, Aspidosperma, and Iboga systems. It is welcome, therefore, to see the preliminary results of an investigation of the biosynthesis of vincamine (10).6 Comparable incorporations were observed for [ar-3H]tryptophan, [ar-3H]stemmadenine (5), and [ar-3H]taber-sonine (9). These results support the proposal7 that vincamine is a transformation... 

Since the last review on Picralima alkaloids was written (for Volume X) activity in this field has considerably abated and in consequence there is comparatively little new work to be reported. The main features of indole alkaloid biosynthesis have now been elucidated and the reader is referred to Battersby (1) for an authoritative summary of this fascinating topic. Preakuammicine (1) appears to be involved in the direct pathway to the Strychnos, Aspidosperma, and Iboga alkaloids, and although it has not been isolated from Picralima it is appropriate to include it here, and to note that its presence in very young seedlings of Vinca rosea has been established (2). Preakuammicine is almost certainly the precursor of akuammicine (2), a transformation which can also be achieved by treatment with base (2). 

Two alternative intramolecular Diels-Alder reactions of the putative alkaloid precursor dehy-drosecondine (70) have been postulated as a branch point in the biosynthesis of aspidosperma and iboga alkaloids <62JA98>. Reaction by path a, in which the acrylate moiety acts as the dienophile generates the iboga skeleton, (69) while path b, with the vinylindole acting as a diene, gives the aspidosperma structure (71) (Scheme 147). 

Dehydrosecodine (97) is believed to be a key intermediate in the biosynthesis of the Aspidosperma and Iboga alkaloids. The dihydro-derivative, secodine (102), has now been synthesized by a route involving a Claisen ortho ester rearrangement [(98) + (99) (100)] and in situ elimination of methanol [(100) - ... 

Wenkert, E., Biosynthesis of indole alkaloids. The aspidosperma and iboga bases, J. Amer. Chem. Soc., 84, 98 (1962). 

Loganin is an iridoid glucoside which occupies a central position in the biosynthesis of Corynanthe, Aspidosperma, Iboga, Ipecacuanha, Cinchona, and structurally simpler monoterpene alkaloids. For a review of the extensive researches that led to confirmation of the key role of loganin in alkaloid biosynthesis, see A. R. Battersby, Biochem. Soc. Symp., 29, 157 (1970) A. R. Battersby, Chem. Soc. Spec. Period. Rep., 1, 31 (1971) A. I. Scott, Accts. Chem. Res., 3, 151 (1970). For a useful account of the chemistry of iridoid glucosides see, J. M. Bobbitt and K. -P. Segebarth in Cyclopentanoid terpene Derivatives, Eds., W. I. Taylor and A. R. Battersby, Marcel Dekker, New York, 1969, p 1. 

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