Asymmetric Total Syntheses of Colchicine, β-Lumicolchicine, and Allocolchicinoid N-Acetylcolchinol-O-methyl Ether (NCME)
A concise and highly enantioselective synthesis of colchicine (>99% ee) in eight steps and 9.3% overall yield, without the need for protecting groups, was developed. A unique Wacker oxidation was used for enabling regioselective construction of the highly oxidized and synthetic challenging tropolone C-ring. Furthermore, asymmetric syntheses of β-lumicolchicine and N-acetylcolchinol-O-methyl ether (NCME) were achieved. Notably, NCME was synthesized from β-lumicolchicine by an unusual decarbonylation and electrocyclic ring-opening cascade reaction.
Liu, Xin,Hu, Ya-Jian,Chen, Bo,Min, Long,Peng, Xiao-Shui,Zhao, Jing,Li, Shaoping,Wong, Henry N. C.,Li, Chuang-Chuang
supporting information
p. 4612 - 4615
(2017/09/12)
Colchicine-protein interactions revealed by transient absorption spectroscopy after in situ photoisomerization to lumicolchicines
Irradiation of colchicine (COL) inside serum albumins (SAs) at 350 nm, results in an efficient isomerization to β- and γ-lumicolchicines (LCs). Laser flash photolysis of pre-irradiated COL/SA complexes leads to detection of long-lived LC-derived triplet excited states (λmax = 370 and 600 nm, τT > 10 μs).
Bartovsky, Pavel,Tormos, Rosa,Miranda, Miguel A.
experimental part
p. 305 - 308
(2010/03/03)
Photochemical Isomerization of Colchicine and Thiocolchicine
The photochemical reactivity of colchicine and thiocolchicine is described. Although the irradiation of colchicine gave a well-known transposition reaction to β- and γ-lumicolchicines, thiocolchicine did not react. Femtosecond transient spectroscopy of colchicine showed a strong band with maximum at 510 nm appearing at τ = 0. It disappeared within few hundred femtoseconds, leaving a broad structureless band with a maximum around 470 nm. A second band is observed around 410 nm. The analysis in time showed that the 510-nm component appeared instantaneously and decayed following a biexponential low with time constants of 300 ± 100 fs and 40 ps. The kinetics at 420 nm has a measurable rise time of 300 ± 150 fs. Quantum mechanical calculations on colchicine showed that this absorption is due to a S 1 → S11 transition. In thiocolchicine, the instantaneous formation of a structure with maxima out of the investigated spectral region was observed. A strong absorption around 650 nm indicated the presence of a band with a maximum at longer wavelengths (> 700 nm) and a peak around 380 nm, which partially coincides with the ground-state absorption and therefore strongly affected by its bleaching. The instantaneous formation of an absorption around 650 nm and its rapid (~500 fs) decay was observed. At shorter wavelengths (400 nm), the decay was fitted with a biexponential curve with the first time constant of about 80 ps. The second part of the decay had a very long tail up to 500 ps. Transient spectroscopy and configuration interaction calculations are in agreement with a mechanism involving a disrotatory cyclization of colchicine in its first excited singlet state. The lack of reactivity observed in thiocolchicine was explained by considering the presence of efficient ISC to the triplet state.
Does the photochemical conversion of colchicine into lumicolchicines involve triplet transients? A solvent dependence study.
beta- and gamma-lumicolchicines are photoproducts formed by the cycloisomerization of the tropolone ring of colchicine (COL) alkaloids. The mechanism of the photoconversion, suggested to involve the triplet state, is examined here by studying the effect of the solvent polarity on the lumicolchicine photoisomer ratio. Triplet COL, detected by laser flash photolysis, is quenched by oxygen, but not by transtilbene or 1-methylnaphtalene. Neither the quantum yield of conversion of COL nor the photoproduct ratio was altered by the presence of oxygen. Likewise, energy transfer to COL from triplet acetone produced by either isobutanal/horseradish peroxidase system or tetramethyldioxetane thermolysis failed to provoke photoreaction of COL. Our data argue against the intermediacy of a COL triplet state in the photoisomerization and stress on the role of specific solvent-solute interactions in determining the partitioning of excited singlet state into the beta- and gamma-isomer formation.
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