Vindoline, ring formation

A rationalization of the generally selective formation of the undesired C-16 -C-14 PREF relative stereochemistry on reaction of the chloro-imine-chloroindoline alkene 17a,b with vindoline (3) may be found in a preferred conformation, 25a or 25b, of the cationic intermediate 25, where the C-3 methylene group hinders approach to one face of the nine-mem-bered ring (Fig. 2). A conformationally more flexible nine-membered ring cationic intermediate 29a,b would be expected to be formed from the chloro derivative of a D-secocleavamine 30. From reaction of such a compound with vindoline (3), under the usual protic acid conditions for cou-... 

Derivatives with five- and six-membered oxygen-containing rings have been isolated when vindoline and deacetylvindoline were treated under superacid conditions.686 Formation of the unexpected oxolane derivatives (R = Ac 4%, R = H 18%) was accounted for by rearrangement through ethyl and hydride shifts (Scheme 5.66). 

Ferric ion-induced coupling of catharanthine (135) and vindoline (140) in aqueous acidic media to produce 3,4 -anhydrovinblastine has been proposed to occur via the formation of a cation radical (136) of the tertiary amine of catharanthine (Scheme 30). Rearrangement and subsequent fragmentation between C16 and C21 leads to ring opening. A second oxidation followed by nucleophilic attack of the diiminium (137) by vindolene (140) results in the formation of iminium (139), which on borohydride reduction yields 3,4 -anhydrovinblastine (77 %) [238]. 

Anodic oxidation (C/LiClOVMeOH) of the aspidofractinine-type alkaloid, kopsamine (577) yielded a dimerization product 579, characterized by the presenee of a central tetrahydrofuran ring and a C2 axis of symmetry (363). Photochemically induced coupling of deacetylaspidospermine (578) gave the dimer 580, charaeterized by a 10, 10 -bond (364). Oxidation of vindoline by horseradish peroxidase gave the 14,3 -linked enamine dimer 581, while similar oxidation of 16-O-acetylvindoline led to the stable conjugated iminium salt, without formation of any dimerization product (365). 

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