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Four new (1-4) and two known (5 and 6) α-pyrone derivatives have been isolated from Alternaria phragmospora, an endophytic fungus from Vinca rosea, leaves. The isolated compounds were chemically identified to be 5-butyl-4-methoxy-6-methyl-2H-pyran-2-one (1), 5-butyl-6-(hydroxymethyl)-4-methoxy-2H-pyran-2-one (2), 5-(1-hydroxybutyl)-4-methoxy-6-methyl-2H-pyran-2-one (3), 4-methoxy-6-methyl-5-(3-oxobutyl)-2H-pyran-2-one (4), 5-(2-hydroxyethyl)-4-methoxy-6-methyl-2H-pyran-2-one (5), and 5-[(2E)-but-2-en-1-yl]-4-methoxy-6-methyl-2H-pyran-2-one (6). Compounds 2 and 4 showed moderate antileukemic activities against HL60 cells with IC50 values of 2.2 and 0.9 μM and against K562 cells with IC50 values of 4.5 and 1.5 μM, respectively.

The synthetic investigation of biologically active natural compounds serves two main purposes: (i) the total synthesis of alkaloids and their analogues; (ii) modification of the structures for producing more selective, more effective, or less toxic derivatives. In the chemistry of dimeric Vinca alkaloids enormous efforts have been directed towards synthesizing new derivatives of the antitumor agents vinblastine and vincristine so as to obtain novel compounds with improved therapeutic properties.

From the aerial parts of Vinca sardoa , seven indole alkaloids were isolated, conoflorine and six plumerane-type indolines, N (1)-methyl-14,15-didehydro-12-hydroxyaspidofractinine, N (1)-methyl-14,15-didehydro-12-methoxyaspidofractinine, N (1)-formyl-14,15-didehydroaspidofractinine, N (1)-formyl-14,15-didehydro-12-hydroxyaspidofractinine and the known, venalstonine and N (1)-methyl-14,15-didehydroaspidofractinine.

Tubulin is the biochemical target for several clinically used anticancer drugs, including paclitaxel and the vinca alkaloids vincristine and vinblastine. This review describes both the natural and synthetic agents which are known to interact with tubulin. Syntheses of the more complex agents are referenced and the potential clinical use of the compounds is discussed. This review describes the biochemistry of tubulin, microtubules, and the mitotic spindle. The agents are discussed in relation to the type of binding site on the protein with which they interact. These are the colchicine, vinca alkaloid, rhizoxin/maytansine, and tubulin sulfhydryl binding sites. Also included are the agents which either bind at other sites or unknown sites on tubulin. The literature is reviewed up to October 1997. © 1998 John Wiley & Sons, Inc., Med Res Rev, 18, No. 4, 259–296, 1998.

The analysis of a series of seventeen vinblastine analogs by circular dichroism is described. Exciton coupling of the indole and indoline chromophores of these compounds provides a general, non-empirical method for the assignment of the C16′ configuration with the bioactive C16′-S and the inactive C16′-R analogs giving rise, respectively, to positive and negative couplets. An analysis of the non-coupled transitions of the CDs indicates that a positive Cotton effect at 305 nm, although empirical, is associated with bioactivity. Theoretical calculations of the UV and CD spectra of vinblastine diastereomers are also described.

Vinblastine and vinorelbine analogues have been synthesised by reacting new versatile electrophilic vindoline derivatives with various 3-substituted indoles. The resulting compounds have been evaluated for their antimitotic properties, but exhibited less potent activities in comparison with the standard binary Vinca alkaloids.

This is a summary of a lecture presented at the 100th Anniversary, Moissan Symposium in Paris on Friday 10th November 2006. In HF/SbF 5 , Vinca alkaloids react selectively at the D’ring of the molecule. In the presence of CHCl 3 (or CCl 4 ), vinorelbine yields 20′,20′-difluoro-3′,4′-dihydrovinorelbine (vinflunine), presently in phase III experimentation for treatment of bladder cancer and non small cell lung cancer.

Publisher Summary This chapter discusses an area of indole alkaloids, which has been neglected in the series for over 30 years—namely, the ajmaline group of alkaloids, where numerous advances in chemistry and biosynthesis have been made recently. The number of known ajmaline structures has grown markedly in recent years to a present count of 77. Some of these might be artefacts and a few structures have not been convincingly determined. In addition, seven bisindole alkaloids containing at least one monomeric ajmalan unit have been isolated, increasing the total number to 84. Ajmaline alkaloids contain the polycyclic ajmalan ring system. The “biogenetic numbering” of Le Men and Taylor is used throughout the chapter. The priority sequence for the C-17 substituents in the Cahn–Ingold–Prelog system is different in the absence and presence of the COOCH, substituent at C-16. All of the ajmaline alkaloids found thus far occur in the plant family Apocynaceae. They have been recognized in the following genera Alstonia , Aspidospenna , Cabucala , Melodinus , Rauvolfia , Tonduzia (Alstonia), and Vinca .

Coupling of catharanthine (IXa), the major alkaloid of Catharanthus roseus, with vindoline leads to vinblastine derivatives which show antitumor activity.