Indole alkaloids Aspidosperma type

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]. 

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. 

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). 

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]. 

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. 

Table II tabulates the plant species which contain the complex indole alkaloids. The letters in this table correspond to the various structural types as coded in Figs. 2 and 3. Types I, II, and III are the major variations of the Cfl-Ci 0 unit which, in combination with tryptamine, formally elaborate the three significantly different groups of complex indole alkaloids Corynanthe, Iboga, and Aspidosperma. Such initial classification follows the outline set by Battersby [3, 3a) and others (2, 4, 5). The...

That the complex indole alkaloids contain a tryptamine unit is a requirement which is not always met at first sight. For example, some alkaloids from the Cinchona and Bemijia species (Rubiaeeae) (Volume VIII, Chapter 10 type Ij, Fig. 2) contain quinoline rings in their overall structures. Nevertheless, it has been shown that tryptophan is readily incorporated into these alkaloids and on this basis they are justly included in Table II. Furthermore, there are a number of complex alkaloids belonging to some Aspidosperma species (Apocynaceae) which seem to have lost the ethylamine side chain of a tryptamine unit (type li. Fig. 2). 

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. 

Quebracho (cortex). The bark of the quebracho tree, Aspidosperma quebracho-bianco (Apocynaceae), a large tree (up to 20 m high), indigenous to the west of South America. The bark contains ca. 1% monoter-penoid indole alkaloids such as yohimbine, aspido-spermine, quebrachamine. The Aspidosperma alkaloids are structurally related to the Catharanthus alkaloid vindoline. Quebracho bark contains over 25 different alkaloids of widely differing types. ... 

Terpenoid indole alkaloids This group of alkaloids is very large and contains more than 3000 compounds. Three types of nucleus occur here the corynanthe, iboga, and aspidosperma ... 

Biogenetic Pathways of the Corynanthe-Aspidosperma and Iboga-type Partial Structures of Monoterpenoid Indole Alkaloids (Carbons indicated by a dotted line may be omitted)... 

Rauwolfia alkaloids a group of about 50 structurally related indole alkaloids firom the roots and rhizomes of various species of Rauwolfa, Aspidosperma and Corynanihe. All R. a. contain a -carbolene skeleton they are classified into 3 types 1. yohimbine (cory-nanthine), 2. ajmaline, 3. serpentine. The large number of R. a. is due to the existence of stereoisomers. Thus Rauwolfia contains seven stereoisomers of yohimbine. 

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). 

B, Iridoid Indole Alkaloids. Most jS-carbolines are derived from tryptamine and the iridoid secologanin (D 6.1.2). In dependence on the structure of the iridoid part alkaloids of the Corynanthe-Strychnos type as well as of the Aspidosperma and Iboga types may be distinguished. The latter are formed by rearrangement of the iridoid part which is shown schematically in Fig. 259 and in detail in Fig. 261. 

The study of Fuji et al. shows that the addition of lithium enolate 75 to ni-troamine 74 is readily reversible quenching conditions are thus essential for getting a good yield of product 76. An equilibrium mixture of the adducts exists in the reaction mixture, and the elimination of either the prolinol or lactone moiety can take place depending on the workup condition (Scheme 2-34). A feature of this asymmetric synthesis is the direct one pot formation of the enantiomer with a high ee value. One application of this reaction is the asymmetric synthesis of a key intermediate for indole type Aspidosperma and Hun-teria alkaloids.68 Fuji69 has reviewed the asymmetric creation of quaternary carbon atoms. 

This biogenetic proposal has spurred interest in the synthesis of structures such as (70). An especially efficient example of the use of intramolecular Diels-Alder reactions to synthesize aspidosperma alkaloids has been developed by Kuehne and co-workers <8373715, 85JOC924, 85JOC4790, 87JOC347). The azepino[4,S-6]indole structure (72) is condensed with a d-haloaldehyde generating (74), which undergoes fragmentation to (75) which contains the secodine synthon. With the secodine type structure only cycloaddition path b is available and aspidosperma structures are formed (76) (Scheme 148). 

---