Sarpagine Alkaloids Research Articles

Biomimetic Entry to the Sarpagan Family of Indole Alkaloids: Total Synthesis of (+)-Geissoschizine and (+)-N-Methylvellosimine.

For Abstract see ChemInform Abstract in Full Text.

General approach for the synthesis of sarpagine indole alkaloids. Enantiospecific total synthesis of (+)-vellosimine, (+)-normacusine B, (-)-alkaloid Q3, (-)-panarine, (+)-Na-methylvellosimine, and (+)-Na-methyl-16-epipericyclivine.

The first total synthesis of (+)-Na-methyl-16-epipericyclivine (9) was completed [from d-(+)-tryptophan methyl ester] in an overall yield of 42% (eight reaction vessels). The optical rotation [[alpha]D +22.8 (c 0.50, CHCl3)] obtained on this material confirmed that the reported optical rotation [[alpha]D 0 (c 0.50, CHCl3)]47 was biogenetically unreasonable. The total syntheses of (+)-vellosimine, (+)-normacusine B, (-)-alkaloid Q3, (-)-panarine, and (+)-Na-methylvellosimine are also described. Moreover, a mixed sample (1:1) of synthetic (-)-panarine and natural (-)-panarine yielded only one set of signals in the 13C NMR; this indicated that the two compounds are identical and further confirmed the correct configuration of (+)-vellosimine, (+)-normacusine B, and (-)-alkaloid Q3. In this approach, the key templates, (-)-Na-H,Nb-benzyltetracyclic ketone 15a and (-)-Na-methyl,Nb-benzyltetracyclic ketone 43 were synthesized on multihundred gram scale by the asymmetric Pictet-Spengler reaction and a stereocontrolled Dieckmann cyclization via improved sequences. An intramolecular palladium (enolate-mediated) coupling reaction was employed to introduce the C(19)-C(20) E-ethylidene function in the sarpagine alkaloids for the first time in stereospecific fashion.

Biomimetic entry to the sarpagan family of indole alkaloids: total synthesis of +-geissoschizine and +-N-methylvellosimine.

A concise synthesis of (+)-geissoschizine (1), a biosynthetic precursor of a variety of monoterpenoid indole alkaloids, from d-tryptophan (19) was performed as a critical prelude to achieving the first biomimetic, enantioselective synthesis of the sarpagine alkaloid (+)-N(a)-methylvellosimine (5). The approach to (+)-geissoschizine was designed to address the dual problems of stereocontrolled formation of the E-ethylidene moiety and the correct relative configuration at C(3) and C(15). Key steps in the synthesis involve a vinylogous Mannich reaction to prepare the carboline 22, which has the absolute stereochemistry at C(3) corresponding to that in 1 and 5, and an intramolecular Michael addition that leads to the tetracyclic corynantheane derivative 24, which possesses the correct stereochemical relationship between C(3) and C(15). Compound 24 was then transformed into 27, the pivotal intermediate in the syntheses of 1 and 5, by a sequence that allowed the stereospecific introduction of the E-ethylidene moiety. Selective reduction of the lactam in 27 followed by removal of the C(5) carboxyl group by radical decarbonylation gave deformylgeissoschizine (2) that was converted into (+)-geissoschizine (1) by formylation. The common intermediate 27 was then converted via a straightforward sequence of reactions into the alpha-amino nitrile 39. The derived silyl enol ether 40 underwent ionization upon exposure to BF(3).OEt(2) to give the intermediate iminium ion 41 that then cyclized in a biomimetically inspired intramolecular Mannich reaction to deliver (+)-N(a)-methylvellosimine (5). This transformation provides experimental support for the involvement of such a cyclization as one of the key steps in the biosynthesis of the sarpagine and ajmaline alkaloids.

General approach for the synthesis of sarpagine/ajmaline indole alkaloids. Stereospecific total synthesis of the sarpagine alkaloid (+)-vellosimine.

[reaction: see text] (+)-Vellosimine has been synthesized enantiospecifically in 27% overall yield from commercially available D-(+)-tryptophan methyl ester via the asymmetric Pictet-Spengler reaction and a stereocontrolled intramolecular palladium-coupling reaction as key steps.

A successful acid promoted asymmetric pictet-spengler reaction of Na-BOC protected tryptophans. Effect of the BOC group on reactivity and stereoselectivity

N a-BOC protected tryptophans 1 and 2 successfully undergo the Pictet-Spengler cyclization with a series of aldehydes in the presence of an acid catalyst ( p-TSA) to furnish a mixture of trans and cis 1,2,3,4-tetrahydro-β-carbolines (3 and 4). During removal of the BOC function with TFA, the mixture of trans (3) and cis (4) isomers was enantiospecifically converted into the trans N a-H 1,2,3,4-teaahydro-β-carboline 5, a key intermediate for the construction of N a,-H substituted sarpagine alkaloids.

Definitive assignment of the 13C NMR signals of the indole C‐3 and C‐3a carbons of the ajmaline, picraline and sarpagine alkaloids

AbstractComparison of a 1H coupled natural abundance 13C NMR spectrum of 1‐oxo‐1,2,3,4‐tetrahydrocarbazole with a single‐frequency experiment in which the hydrogens three bonds away from C‐3 (indole numbering) were irradiated allowed the unambiguous distinction of the C‐3 and C‐3a signals. The results can be extrapolated for the assignment of the same signals in the ajmaline, picraline and sarpagine alkaloids, which also contain a carbonyl group as the substituent at the C‐2 position of the indole skeleton. The effect of this carbonyl group on the chemical shifts of the benzenoid carbons is also discussed.

Quaternary alkaloids from Peschiera fuchsiaefolia

From an ethanolic extract of Peschiera fuchsiaefolia three quaternary alkaloids have been isolated and their structures determined from their spectral data as 12-methoxy-4-methylvoachalotine, 12-methoxy-4-methylvoachalotine ethyl ester and fuchsiaefoline. Analyses of the 13C NMR spectra of some sarpagine alkaloids were carried out to confirm the structures of these compounds.

A 400 MHz1H-NMR Study of Seven Sarpagine-Type Alkaloids

The chemical shifts and most of the main coupling constants of seven sarpagine alkaloids 1- 7 have been determined in a 400 MHz (1)H-NMR study.