19S-Vindolinine

This group is dominated by vindolinine (19/J-vindolinine, 109), 19-epivindolinine (19S-vindolinine, 137), and their A b-oxides, new sources for which are listed in Table I. The alkaloids isolated from the leaves of Catharanthus roseus and formulated as 16-epi-195-vindolinine 150) and its A -oxide 149) were later shown to be 19S-vindolinine (137) and its N-oxide, and the apparently puzzling features in the NMR spectrum of the base 137 were explained 151). If kept in chloroform or deuterochloroform at room temperature, 195-vindolinine (137) isomerizes to 19/ -vindolinine (109) via a mechanism that must involve a series of equilibria in which N y is first protonated and then the 7,21-bond is broken to give an iminium ion 138 in which proton exchange and inversion of C-19 are possible. Accordingly, the NMR spectrum of 19S-vindolinine, if recorded within 2 h of dissolution in chloroform, is consistent with that of structure 137. But after 36 h the isomerization is more or less complete, and the spectrum of 19/ -vindolinine (109) is obtained. The C NMR spectrum naturally undergoes similar changes. 

Didehydroervatamine, in E-10191 Ervincine, in P-10116 16j5-Hydroxy-19/ -vindolinine, in V-10024 16jff-Hydroxy-195-vindolinine, in V-10024 Lundurine B, in L-30059 3-Oxovincadifformine, in V-10022 5-Oxovincadifformine, in V-10022 Rhazimol, in A-10036 195-Vindolinine A-oxide, in V-10024... 

CP-MAS has allowed the study of conformations and cross-linkages in natural and synthetic polymers, and of structures of proteins, nucleic acids, phospholipid membranes, etc. The field is still in its infancy and its applications will undoubtedly grow. The CP-MAS solid state C-NMR spectrum of 19S-vindolinine, has been studied by Atta-ur-Rahman and coworkers at H.E.J. Research Institute of Chemistry, and it is shown in Figure 4.16. It represents the first example of a CP-MAS spectrum of a solid Aspidosperma alkaloid ever recorded. 

Figure 4.16. Above Broad-band C-NMR of 19S -vindolinine (solution spectrum) below solid-state C-NMR spectrum of the same compound.

The 2D-homonuclear correlated NMR spectrum of 19S-vindolinine is presented in Figure 5.70. The two H-NMR spectra appear on the two axes, and each proton in this fairly complex molecule has been assigned on the basis of the coupling cross peaks. 

The structure of 14, 15 -dihydropycnanthine has been revised to [533] from a comparison of its 13C NMR spectrum with that of villalstonine [530] and of vindolinine [439]. That [533] belongs to the 19 S series is shown by the similarity of its 18 -proton and carbon parameters to those in 19 -epivindolinine [534] (compare values in vindolinine [535]). The similarity of C(21 ) shifts in 19 -epivindolinine and in 14, 15 -dihydropycnanthine shows the absence of the endocyclic homoallyl effect. (319)... 

Yet another rearrangement of a tabersonine derivative has been reported. 19-Iodotabersonine (202), prepared from vindolinine, when heated with diazabi-cycloundecene in DMSO, gives mainly the expected A18-tabersonine, together with the cyclobutane derivative (203) and an optically inactive non-basic indole derivative, for which the structure (204) has been proposed.118 A much-improved yield of (204) (78%) can be obtained if the reaction is conducted in DMF in the presence of sodium acetate. One of the possible mechanisms for the formation of (204) is illustrated if correct, this requires the presence of water in the reaction mixture. 

The structure of baloxine (236) has been confirmed by partial synthesis from vindolinine,110 which has previously been converted into 19-hydroxytabersonine (237). The tetrahydropyranyl ether (238) of the (19.S)-epimer, on hydroboration-oxidation, gave a mixture of C-14 epimeric alcohols (239) on oxidation and removal of the tetrahydropyranyl ether grouping, these gave baloxine (236) (Scheme 34). Its formulation as (19S)-hydroxy-14-oxovincadifformine is thus confirmed. 

In their synthesis (354) of vindolinine (109) and its 16- and 19-diastere-oisomers, L6vy and collaborators formed the 2,19-bond by sonochemical cyclization of the radical produced by treatment of 19-iodotabersonine (278) with sodium. The yields and proportions of the four 16- and 19-stereoisomers varied according to the experimental conditions. At lower ultrasonic intensities, vindolinine (109) and 16-epivindolinine (612) were obtained in a 1 2 ratio at higher intensities all four stereoisomers were produced (Scheme 82). 

With the structure of vindolinine revised (50), Potier and co-workers turned their attention to melobaline, which had previously (19) been assigned a structure in the vindolinine series. A reevaluation of the PMR spectrum and determination of the CMR spectrum resulted in a revision of the structure of melobaline (51). 

Epivindolinine (153) was obtained as an amorphous gum having a mass spectrum identical with that of vindolinine. The only important... 

Also isolated from M. balansae were two closely related alkaloids, vindolinine N-oxide (154) and 19-epivindolinine N-oxide (155) (48). 

E. Vindolinine-type alkaloids 19-Epivindolinine (153) 19-Epivindolinine A-oxide (154)... 

The n.m.r. spectrum of vindolinine enabled the structure to be corrected to (98). Formerly a structure (99) in which C-19 is attached to C-6 was thought to be correct. The chemical shifts in the n.m.r. spectrum [figures on (98] of vindolinine compared well with those for venalstonine (36) (see p. 189). More importantly it could be shown that the spectrum had one more non-aromatic, non-protonated carbon and one less non-aromatic methine signal than required by the old structure, and that the extra quaternary carbon had a chemical shift appropriate for C-2, an amino carbon, and the methylene carbon one appropriate for C-6. 

The branches and leaves of Melodinus celastroides have yielded 19-epi-vindolinine, (19/ )- and (19S)-hydroxytabersomne, (-)-tabersonine, (-)-venalstonine, (-)-vindolinine, and five new alkaloids, which are 14,15-dehydroisoeburnamine, buxomeline (189), and three alkaloids whose structures have not yet been disclosed, viz. melonine, melonine TVb-oxide, and methylene-bis-l,r-melonine. The structure (189) of buxomeline was deduced almost entirely from its spectroscopic properties the presence of both Nb-carbinolamine and carbinolamine ether functions is unusual. 

Details of the X-ray crystal structure determination of meloscandonine and Na-methyl-19-cpi-vindolininol have been published. This latter derivative is obtained by the Xa-methylation of vindolinine, followed by reduction (LiAlRi) and epimerization (CF3CO2H) this work also serves to confirm the structure of 19-ep/-vindolinine, an alkaloid isolated earlier from Melodinus balansae. "... 

For analysis of alkaloids in Catharanthus roseus roots, Ferreres et al. describe a phytochemical study on this species roots. Alkaloids in aqueous extracts, the usual form of consumption of this matrix, were studied by HPLC-DAD-ESl-MS/MS, which allowed the identification of 19-S-vindolinine, vindolinine, ajmalicine and an ajmalicine isomer, tabersonine, catharanthine, serpentine, and a serpentine isomer. Quantification of the identified compoimds revealed that serpentine and its isomer were predominant (64.7 %) over the other alkaloids, namely, vindolinine and its isomer (23.9 %), catharanthine (7.7 %), and ajmalicine (3.8 %). The proposed procedures revealed to be simple, sensitive, and reproducible [13]. 

---