Photochemical Isomerization of Colchicine and Thiocolchicine

Abstract

The photochemical reactivity of colchicine and thiocolchicine is described. Although the irradiation of colchicine gave a well-known transposition reaction to -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 f S 11 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.Colchicine (1) is the major alkaloid of Colchicum autumnale (autumn crocus) and Gloriosa superba (flory lily), Liliacee. It is an ancient drug used in medicine for its antimitotic, antiinflammatory, and antineoplastic effects. 1,2 It has been used as a neurotoxin in animal models of Alzheimer's disease and epilepsy. 3 Several derivatives have been synthesized in order to improve antitumor activity. [4][5][6] The irradiation of colchicine leads to the formation of -and γ-lumicolchicine (3 and 4) (Scheme 1). Prolonged irradiation times lead to the formation of R-lumicolchicone (2) (Scheme 1). 7-21 -Lumicolchicine is a biologically active compound. 22 Previous photolysis studies indicated that the quantum yield of colchicine conversion depends on solvent polarity. 23 This behavior was explained by assuming the formation of a solvation complex in the ground state. The nature of the excited state responsible for the formation of photoproducts has not been determined; the authors proposed that colchicine isomerization occurs from the triplet excited state. However, in a subsequent study, they did not observe any quenching effect of several triplet acceptors on the reactivity. 24 In a previous paper, we found that transient absorption spectrosc...

Ultrafast chemistry in complex and confined systems

“…17 Most recently, ultrafast studies have shown that the important drug molecule cholchicine involves isomerization. 18 The dynamics of cis-trans photoisomerization of a polyene depends on the viscosity of the medium. 19 At a very high viscosity, the rate of photoisomerization (k iso ) is inversely proportional to bulk viscosity (Smoluchowski limit).…”

Photoinduced Skeletal Rearrangement of N-Substituted Colchicine Derivatives

“…40 This reasoning clearly explains the lack of photoreactivity of thiocolchicine, which forms weak or no hydrogen bonds. 29 , 34 , 36 …”

“… 12 − 27 When colchicine is exposed to sunlight, it transforms to a mixture of α-, β-, and γ-lumicolchicine, where β- and γ-lumicolchicine are stereoisomers and α-lumicolchicine is a cyclobutane dimer of β-lumicolchicine ( Figure 1 ). 28 , 29 This process highly depends on the solvent polarity and can be connected to the formation of a complex with a solvent in the ground state. 30 , 31 …”

“…This information suggests that photostability of colchicine derivatives depends on the C-ring substituents. 29 , 34 − 36 …”

β-Phenylethylamines and the isoquinoline alkaloids

“…101 Details of a solid-phase preparation of N-alkylnaltrindoles, 102 and of preparations of other indoles of types 191, 103 119 The failure of thiocolchicine to undergo photochemical isomerisation to analogues of b-and c-lumicolchicines has been studied and attributed to an efficient ISC to the triplet state. 120 A total synthesis of (−)-(7S)-allocolchicine 212b has been achieved from the benzosuberone 207. This ketone was converted into the bromo-olefin 208a, which on treatment with N-bromosuccinimide, followed by solvolysis of the product, yielded the racemic alcohol 208b.…”