Chapter 8 Colchicine and Related Compounds

Antitumor Agents. 192. Antitubulin Effect and Cytotoxicity of C(7)-Oxygenated Allocolchicinoids

“…The reaction mixture was stirred for 30 h at room temperature. At the completion of the reaction, 2 was converted to its methylated form 3 and was easily separated from 1 by chromatography using 5% CH 3 7-Deamino-7-oxo-5,6-dehydrocolchinol Methyl Ether (8) To a 15 ml flask fitted with dry N 2 , dry THF (5 ml) was introduced. It was cooled to -78°C, and 2 M lithium diisopropylamide (in heptane-THF-ethylbenzene, 0.16 ml) was introduced.…”

“…Removal of solvent afforded crude compound (42.3 mg), which was purified by preparative TLC with 20% acetone-hexane. Crystallization from dibutyl ether and recrystallization from CH 3 (9) To a solution of 6 (13 mg, 0.04 mmol) in a mixture of CH 2 Cl 2 -CH 3 OH was added NaBH 4 (20 mg, 0.53 mmol), and the solution was stirred at room temperature for 30 min. The reaction mixture was acidified with 50% acetic acid and then extracted with CH 2 Cl 2 (3 × 5 ml).…”

Total Biosynthesis of the Tubulin-Binding Alkaloid Colchicine

“…The bioactivity of 1 is largely attributed to this unique tropolone ring system, as multiple precursors to colchicine with this scaffold exhibit tubulin-binding activity and cytotoxicity, while precursors lacking the tropolone moiety (e.g., O -methylandrocymbine) seem to have limited cytotoxic effects. , Though tropolone formation is critical to the pharmaceutical properties of these alkaloids, specific modification of the lone nitrogen atom is also important, as 1 , which possesses an N -acetyl group, has been shown to have the highest tubulin affinity and corresponding bioactivity of the colchicine-related alkaloids . Additionally, 1 is the most abundant alkaloid present in the native Colchicum and Gloriosa species, which implies its importance within the chemical ecology of these plants. Therefore, processing of this nitrogen atom to form the N -acetyl moiety, and thus 1 , is paramount not only for establishing the full biosynthesis of this natural product, but also for better understanding the role that these late stage nitrogen-tailoring reactions have on the biological effects of this group of alkaloids.…”

Liliaceae Juss.

“…Colchicine interferes with microtubular -dependent cell functions by reversibly binding to tubulin protein and thus blocking polymerization. Storage of large amounts in corms occurs especially in spring (Wildman 1960b) (Figure 46.12). Another effect of this interference with microtubules is inhibition of migration and lysosomal degranulation of polymorphonuclear leukocytes.…”