Modifications on the basic skeletons of vinblastine and vincristine - PubMed (original) (raw)
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Modifications on the basic skeletons of vinblastine and vincristine
Péter Keglevich et al. Molecules. 2012.
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.
Figures
Figure 1
Structures of vinblastine (1) and vincristine (2).
Scheme 1
Preparation of 17-desacetylvinblastine-16-amide (5).
Scheme 2
Selective desacetylation of vinblastine (1).
Scheme 3
Amino acid derivatives of vinblastine.
Scheme 4
Hydrazide derivatives 8 and 9 of vinblastine (1).
Scheme 5
Iodination reactions on vinblastine (1).
Scheme 6
Bromination and formylation of vinblastine (1).
Scheme 7
Reactions of 12′-iodovinblastine (10).
Scheme 8
Reduction of vinblastine (1).
Scheme 9
Fluorination reaction of vinblastine (1).
Scheme 10
Nitration of vinblastine (1).
Scheme 11
Coupling of vinblastine (1) with amino acids.
Scheme 12
Vinblastine derivatives conjugated with carrier peptide.
Scheme 13
Synthesis of vinorelbine (33).
Scheme 14
Oxidation of vinblastine (1) to vincristine (2).
Scheme 15
Ring transformation reaction.
Scheme 16
Preparation of vinamidine (35).
Scheme 17
Spiro-substituted dimer alkaloids.
Scheme 18
Deacetylation of vincristine (2).
Scheme 19
Reduction of vincristine (2).
Scheme 20
Nitration of vincristine (2).
Scheme 21
Iodinated derivatives of vincristine (2).
Scheme 22
Selective deacetylation of vincristine (2).
Scheme 23
Detailed synthesis of vinflunine (58).
Scheme 24
Preparation and reaction of 9-chlorocatharanthine (59).
Scheme 25
Building in an oxirane ring to catharanthine (3).
Scheme 26
Preparation of leurosidine (65).
Scheme 27
New derivatives of catharanthine.
Scheme 28
Fluoro-substituted dimeric alkaloids.
Scheme 29
Coupling with saturated vindoline.
Scheme 30
Carbamates of vinblastine.
Scheme 31
Amide substitued anhydrovinblastine derivatives.
Scheme 32
Modification of C-20 ethyl substitutent of vindoline.
Scheme 33
Vinblastines substituted at the vindoline D-ring.
Scheme 34
Coupling vindoline (4) with substituted catharanthines.
Scheme 35
Coupling in a one-step reaction.
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