Alkaloids aspidospermine

Especially when combined with the Pummerer-type preparation, thiocarbenium species become valuable carbon electrophiles for various ring closure reactions. At nearly any time in the course of the synthesis, the thiocarbenium species can be set free, e.g. from the nonproblematical sulfide function under essentially mild, oxidative conditions, as demonstrated in the synthesis of the pentacyclic precursor (122) to aspidospermine alkaloids from (121 Scheme 59). The sulfur, if not required for the target molecule, can be taken away reductively, after the ring closure reaction (cf. Scheme 37, Section 4.2.2.1). 

The availability of 19-iodotabersonine (278) has allowed the partial synthesis of several aspidospermine alkaloids. For example, Komblum oxidation of 278 under anhydrous conditions gives 19-oxotabersonine, which on hydrogenation of the 14,15-double bond affords (-)-minovindne (316)... 

One of the most original and ingenious routes to the synthesis of the aspidospermine alkaloids is the tandem aza-Cope rearrangement-Mannich cyclization route developed by Overman and collaborators. This was originally introduced in a synthesis of 11-methoxytabersonine (q.v.), and it has also been applied to the synthesis of deoxylimapodine (479) and N-acetylaspidoalbidine (480) (308). This work has already been discussed in an earlier volume (4), to which the reader is referred for details. 

Saxton reviews the isolation and synthesis of the aspidospermine alkaloids in Chapter 1, thereby updating the last review, which appeared in this series over 20 years ago. The chapter complements a contribution (also by Saxton) in Volume 50 that specifically focused on the synthetic highlights of this intensely studied aspect of indole alkaloid chemistry. 

Enamino ketoester 159 (in equilibrium with the corresponding imidizolidine) efficiently underwent aza-annulation with acryloyl chloride in the presence of pyridine and DMAP to give 160 (eq. 34).60 This dihydropyridone was then converted to 161, the pentacyclic skeleton of the 21-epimer of the aspidospermine alkaloids. 

A procedure has been established for the synthesis of certain aspidospermine alkaloids, based on the addition of an enolate of methyl 2-indolylacetate to a pyridinium salt (367), followed by acid-catalyzed cyclization of the resulting 1,4-dihydropyridine (368) to the tetracyclic structure (369) (Scheme 124) <84H(21)325,89J0C1166,94T5233>. 

Biolatto B, Kneeteman M et al (1999) Diels-Alder reactions of lV-tosyl-3-nitroindole and dienamides synthesis of intermediates of Aspidospermine alkaloids. Tetrahedron Lett... 

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