Aromatic Electrophilic Substitutions on Vindoline.

Abstract

Alkaloids U 0600Aromatic Electrophilic Substitutions on Vindoline. -Nitration of 10-bromo derivative (V) leads to the unexpected, anomalous 12-bromo-10-nitrovindoline (VI) and appears to be a further example of the rearrangement discovered by Reverdin. Nitration of the 10-chloro analogue (VII) leads to the expected derivative (VIII). -(GORKA-KERESKENYI, A.; SZABO, L.; HAZAI, L.; LENGYEL, M.; SZANTAY, C. J.; SANTA, Z.; KALAUS, G.; SZANTAY*, C.; Heterocycles 71 (2007) 7, 1553-1563; Dep. Org. Chem. Technol., Budapest Univ. Technol. Econ., H-1521 Budapest, Hung.; Eng.) -K. Woydowski 44-184

Attempted Synthesis of Vinca Alkaloids Condensed with Three-Membered Rings

“…The Simmons–Smith reaction resulted stereospecifically in 8 14,15-bromocyclopropanovindoline (31% yield) and 10 14,15-iodocyclopropanovindoline (9% yield). By achieving the reaction with 10-bromovindoline ( 7 ) [18], the 9 bromocyclopropane and 11 iodocyclopropane derivatives were obtained in yields of 40% and 22%. The configurations of the 14, 15, and 22 carbon atoms were determined by NMR spectroscopy (14:( S ), 15:( R ), and 22:( S )).…”

Cyclopropanation of Some Alkaloids

“…The first task was to protect position 10 of vindoline, because in the presence of sodium nitrite used in the preparation of the corresponding azide, a nitrosation reaction took place in position 10, resulting in 10-nitrosovindoline [44]. In this procedure a bromo substituent was used to protect position 10 (Scheme 4).…”

“…10-Bromovindoline (10) was prepared by us from vindoline (8) in a simple bromination reaction using N-bromosuccinimide [44]. 14,15-Dihydrovindoline (11) is known from the literature [48], and was obtained by catalytic hydrogenation of vindoline (8).…”

“…The 14,15-cyclopropano derivative of 10-bromovindoline (26) was previously prepared by us [40] from 10-bromovindoline [44] (10) in the reaction with diiodomethane and with diethylzinc in dichloromethane (Scheme 9). 10-Bromo-14,15-cyclopropanovindoline (26) was treated in methanol with sodium borohydride in the presence of palladium on charcoal, which resulted in the expected 14,15-cyclopropanovindoline (27) unsubstituted in position 10.…”

Modifications on the Basic Skeletons of Vinblastine and Vincristine

“…Reactions and derivatives of vindoline for the synthesis of vinblastine were scarcely investigated. The reactivity of the aromatic ring of vindoline was presented by Szántay et al [40], but the new vindoline derivatives were not used for the preparation of dimer alkaloids.…”