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Review
. 2012 May 18;17(5):5893-914.
doi: 10.3390/molecules17055893.

Modifications on the basic skeletons of vinblastine and vincristine

Péter Keglevich  1 , László Hazai, György Kalaus, Csaba Szántay
Affiliations
Review

Modifications on the basic skeletons of vinblastine and vincristine

Péter Keglevich et al. Molecules. .

Abstract

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.

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Figures

Figure 1
Figure 1
Structures of vinblastine (1) and vincristine (2).
Scheme 1
Scheme 1
Preparation of 17-desacetylvinblastine-16-amide (5).
Scheme 2
Scheme 2
Selective desacetylation of vinblastine (1).
Scheme 3
Scheme 3
Amino acid derivatives of vinblastine.
Scheme 4
Scheme 4
Hydrazide derivatives 8 and 9 of vinblastine (1).
Scheme 5
Scheme 5
Iodination reactions on vinblastine (1).
Scheme 6
Scheme 6
Bromination and formylation of vinblastine (1).
Scheme 7
Scheme 7
Reactions of 12′-iodovinblastine (10).
Scheme 8
Scheme 8
Reduction of vinblastine (1).
Scheme 9
Scheme 9
Fluorination reaction of vinblastine (1).
Scheme 10
Scheme 10
Nitration of vinblastine (1).
Scheme 11
Scheme 11
Coupling of vinblastine (1) with amino acids.
Scheme 12
Scheme 12
Vinblastine derivatives conjugated with carrier peptide.
Scheme 13
Scheme 13
Synthesis of vinorelbine (33).
Scheme 14
Scheme 14
Oxidation of vinblastine (1) to vincristine (2).
Scheme 15
Scheme 15
Ring transformation reaction.
Scheme 16
Scheme 16
Preparation of vinamidine (35).
Scheme 17
Scheme 17
Spiro-substituted dimer alkaloids.
Scheme 18
Scheme 18
Deacetylation of vincristine (2).
Scheme 19
Scheme 19
Reduction of vincristine (2).
Scheme 20
Scheme 20
Nitration of vincristine (2).
Scheme 21
Scheme 21
Iodinated derivatives of vincristine (2).
Scheme 22
Scheme 22
Selective deacetylation of vincristine (2).
Scheme 23
Scheme 23
Detailed synthesis of vinflunine (58).
Scheme 24
Scheme 24
Preparation and reaction of 9-chlorocatharanthine (59).
Scheme 25
Scheme 25
Building in an oxirane ring to catharanthine (3).
Scheme 26
Scheme 26
Preparation of leurosidine (65).
Scheme 27
Scheme 27
New derivatives of catharanthine.
Scheme 28
Scheme 28
Fluoro-substituted dimeric alkaloids.
Scheme 29
Scheme 29
Coupling with saturated vindoline.
Scheme 30
Scheme 30
Carbamates of vinblastine.
Scheme 31
Scheme 31
Amide substitued anhydrovinblastine derivatives.
Scheme 32
Scheme 32
Modification of C-20 ethyl substitutent of vindoline.
Scheme 33
Scheme 33
Vinblastines substituted at the vindoline D-ring.
Scheme 34
Scheme 34
Coupling vindoline (4) with substituted catharanthines.
Scheme 35
Scheme 35
Coupling in a one-step reaction.
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References

    1. Brossi A., Suffness M. The Alkaloids. Vol. 37. Academic Press Inc.; New York, NY, USA: 1990. Antitumor Bisindol Alkaloids from Catharanthus Roseus (L.) pp. 1–240.
    1. Bölcskei H., Szabó L., Szántay C. Synthesis of vinblastine derivatives. Front. Nat. Prod. Chem. 2005;1:43–49. doi: 10.2174/1574089054583849. - DOI
    1. Eli Lilly Company, Neue Aminderivate von Vinblastin, Leurosidin und Leurocristin und Verfahren zu ihrer Herstellung. 22415980. DE Patent. 1974 [Chem. Abstr. 1974, 82, 579967b]
    1. Barnett C.J., Cullinan G.J., Gerzon K., Hoying R.C., Jones W.E., Newlon W.M., Poore G.A., Robison R.L., Sweeney M.J., Todd G.C. Structure-activity relationships of dimeric Catharanthus alkaloids. 1. Deacetylvinblastine amide (vindesine) sulfate. J. Med. Chem. 1978;21:88–96. - PubMed
    1. Thimmaiah K.N., Lloyd W.D., Sethi V.S. A simple method for the chemical modification of antitumor Catharanthus Vinca alkaloids. Ind. J. Chem. Sect. B: Org. Chem. Med. Chem. 1990;29:678–680.

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