Tabersonines

Tabersonine (108), clearly a reduced and simplified version of the second-half of the alkaloids 22, was originally isolated inoxsi Pimsonia tabemaemontane V. and is considered to be a simplified parent of a rather more elaborate subgroup of indole alkaloids. 

Imanishi, T., Shin, H., Yagi, N., Hanaoka, M. (1980) l,6-Dihydro-3(2H)-Pyridinones as Symmetric Intermediates. Formal Synthesis of ( )-Tabersonine and ( )-Catharanthine. Tetrahedron Letters, 21, 3285-3288. 

Scheme 6.17 gives some examples of the orthoamide and imidate versions of the Claisen rearrangement. Entry 1 applied the reaction in the synthesis of a portion of the alkaloid tabersonine. The reaction in Entry 2 was used in an enantiospecific synthesis of pravastatin, one of a family of drugs used to lower cholesterol levels. The product from the reaction in Entry 3 was used in a synthesis of a portion of the antibiotic rampamycin. Entries 4 and 5 were used in the synthesis of polycyclic natural products. Note that the reaction in Entry 4 also leads to isomerization of the double bond into conjugation with the ester group. Entries 1 to 5 all involve cyclic reactants, and the concerted TS ensures that the substituent is introduced syn to the original hydroxy substituent. 

Rawal and Kozmin have utilized a Reissert type reaction in the total synthesis of tabersonine. The requisite nitro ketone is prepared by SNAr reaction of o-nitrophenylphenyliodonium fluoride with ketone silyl enol ether (Scheme 10.10).96... 

Among plumeran alkaloids isolated from the leaves of T. coffeoides (Hazunta modesta), two minor compounds were not previously discussed (70). One was recognized as 3-oxotabersonine (68, C21H22N203, MP 151.5-153°C, [a]D -11.4°) identical to the product isolated by Sakai from the seeds of Amsonia elliptica (198). Compound 68 was also obtained in 32% yield by KMn04 oxidation of tabersonine (67). 

The second alkaloid (C21H26N204) was recovered in very small amount and shown to belong to the tabersonine subtype from the UV absorptions ((3-anilinoacrylic chromophore) and from the peaks at m/z 156 (281) and 214 (282) in its MS. On acetylation, a diacetate (M + 454) was formed and the peak at m/z 156 was shifted 84 amu to m/z 240 (283). These data are compatible with a 14,15-dihydroxyvincadifformine structure (76) for this compound however,... 

Coupling of the more activated enamine 335, obtained in two steps from tabersonine, with 21-cyano-20-epipandoline (331) in the presence of AgBF4 in THF solution gave the dimer 334 in 20% yield. Its structure was based on spectral data, particularly CMR. Diagnostic were the chemical shifts for C-2 at 104.1 ppm (versus 103.4 ppm in ervafoline) and the upfield shift of C-6 at 35.3 ppm (ascribed to the -y effect). 

Perivine 25 exhibits an enhanced local anesthetic activity with respect to cocaine in the rabbit-comea test (230). Tabersonine (67) shows 25% of the hypotensive activity of reserpine on cats, ( )-vincadifformine shows 50% activity, whereas (—)-vincadifformine (ent-10) is inactive (231). 

Taber abraser wear test, 9 713-714 Tabersonine, 2 98 Table of Isotopes, 24 754 Table representation, in chemoinformatics, 6 3-6... 

SCHEME 4. Catharanthine 3 and tabersonine 4, natural compounds containing a cyclohexene moiety. These may derive from in vivo Diels-Alder reactions53... 

Deacetylakuammiline (64) 10-Hydroxy-deacetylakuammiline (68) Pleiocarpamine (55) Akuammicine (49) Xylosyloxyakuammicine Dihydrocondylcarpine Vinervine Tabersonine (38) + ... 

Almost nothing is known about the biosynthetic pathway between a Corynanthe intermediate and the first Aspidosperma alkaloid tabersonine (38) and, indeed, the first Iboga alkaloid catharanthine (4). Thus, the focus of further work has been the intermediates involved in the pathway... 

Intrigued by the hypothesis of a dehydrosecodine (120) as a key bioge-netic intermediate in the natural generation of alkaloid structures of both the Aspidosperma (tabersonine, 121) and the Iboga (catharanthine, 21) types (Scheme 33) 108, 109) we developed efficient biomimetic synthe-... 

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