Gelsemine skeleton

Cis- and tranr-isomers are generated in a 1 1.43 ratio. This reaction was the key step in a concise synthesis of cis and tra j-lauthisan <90T4487>. A Claisen rearrangement of enol silyl ether was also used to produce the gelsemine skeleton <87TL1035>. 

A soln. of ethyl 3-[octahydro-3a-(methoxymethyl)-2-methyl-l-(phenylthio)-3,6-dioxo-[li/]isoindol-4-yl]-2-propenoate in benzene treated with 2 eqs. BujSnH and a little AIBN in the same solvent over 10 h ethyl octahydro-3a-(methoxymethyl)-2-methyl-3,6-dioxo-l,4-methano[l //]isoindole-8-acetate. Y 83%. The ring system is the basic component of the gelsemine skeleton. F.e.s. J.-K. Choi et al., J. Org. Chem. J4, 279-90 (1989) 8-methyleneperhydro-3-indolizidinones s. J.M. Dener et al., ibid. 53, 6022-30 (1988). 

The humantenine-type Gelsemium alkaloids, which so far include human-tenine, humantenirine, and rankinidine, are oxindole alkaloids with a novel skeleton similar to that of gelsemine but lacking a bond between C-6 and C-20. From a biogenetic viewpoint, humantenine-type alkaloids are less evolved than those of the gelsemine series and might well be immediate precursors of them... 

However, the proposed in vivo transformation of anhydrovobasinediol to gelsemine might involve a series of more extensive alterations of the molecular skeleton which presumably would include (1) oxidation of the 2,7 double bond, (2) an acid-induced 2,7 shift, and (3) allylic rearrangement of the C-20 ethylidene side chain to a C-20 vinyl, so that a humantenine-type precursor... 

In an elegant approach to gelsemine [238] based on a similar strategy the cationic aza-Cope rearrangement was superseded by a simple Mannich reaction because the twistane skeleton is more highly strained. However, the desired transformation is achievable using the anionic version. 

In formic acid, the enamine is protonated on carbon to give the very electrophilic immonium ion 208 which cyclises in conformation onto the enol 208a in an intramolecular Mannich reaction to give the bicyclic skeleton 203 required for gelsemine. 

For reasons of brevity, some skeletal variations are not clearly defined in Figs. 2 and 3 and some have been omitted. In particular, the picraline (Volume VIII, p. 147), the echitamine (Volume VIII, p. 174) 78), and the aspidodasycarpine 53) skeletons have been merged into type If. The new alstophylline type 39, 40) is somewhat hidden in the Id reprepresentation. Gelsemine (Volume VIII, p. 95) has been included in the oxindole type Ic. Type Ila Iboga) includes several closely related rearranged alkaloids (Volume VIII, Chapter 9) which are not shown in Fig. 3. An unusually modified Aspidosperma structure 83) is related to type III6 and is listed as such. 

In the synthesis of the alkaloid Gelsemine, the intramolecular cyclization catalyzed by AgOTf and Ag2C03 of a carbamoyl chloride to an enamide function provided the polycylic skeleton of the natural product in an elegant and efficient way (eq 67). ... 

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