29  2000 American Society for Photobiology 0031-8655/00 $5.00+0.00 Photochemistry and Photobiology, 2000, 71(1): 29–34 The Photochemical Behavior of Colchicone and Thiocolchicone Laura Bussotti 1 , Maurizio D’Auria* 2 , Paolo Foggi 3 , Giordano Lesma 4 , Roberto Righini 5 and Alessandra Silvani 4 1 LENS, largo E. Fermi, Firenze, Italy; 2 Dipartimento di Chimica, Universita ` della Basilicata, Potenza, Italy; 3 Dipartimento di Chimica, Universita ` di Perugia, Perugia, Italy; 4 Dipartimento di Chimica Organica e Industriale, Milano, Italy and 5 Dipartimento di Chimica, Universita ` di Firenze, Firenze, Italy Received 8 July 1999; accepted 28 September 1999 ABSTRACT The irradiation of colchicone 5 led to the formation of lumicolchicone 7. The same reaction cannot be obtained by using thiocolchicone 6 as substrate. Transient absorp- tion spectroscopy of colchicone and -lumicolchicone showed that probably the photoisomerization occurred on colchicone in its first excited singlet state. The spec- troscopic data are in agreement with the hypothesis that lumicolchicone was generated in the ground state from the S 1 state of colchicone without the presence of any intermediate. Semiempirical calculations on colchicone and thiocolchicone showed that the highest single occu- ped molecular orbital and the lowest unoccupied molec- ular orbital of the singlet excited colchicone can give a disrotatory ring closure to 7, while thiocolchicone cannot give the same type of process. INTRODUCTION Colchicine 1, the major alkaloid of Colchicum autumnale, is an ancient drug used in medicine for its antimitotic, antiin- flammatory and antineoplastic effects (1,2). Since its isola- tion in 1820 (in a relatively pure state), 1 has been the object of intense structural investigations culminating in 1945 with the proposal that it contains a methyl tropolone moiety, in addition to a trimethoxybenzene ring and a seven-membered ring. Subsequently, a large number of derivatives have been prepared, with the aim to improve the pharmaceutical profile of the natural product, decrease the extreme toxicity (3) and unravel the complex structure–activities relationships. From the chemical point of view, the methyl tropolone ring is the most intriguing portion of the molecule, on which a large number of reactions can be performed, such as facile acid and alkaline hydrolysis (4), benzylic acid rearrangement (5), ipso- and telenucleophilic substitutions (6,7), Diels–Al- der cycloadditions with several hetero- and carbodienophiles (8), singlet oxygen addition (9) and photochemical rear- *To whom correspondence should be addressed at: Dipartimento di Chimica, Universita ´ della Basilicata, Via N. Sauro 85, 85100 Po- tenza, Italy. Fax: +39 0971 202223; e-mail: dauria@unibas.it rangement (10–25). The last-mentioned reaction affords the so-called lumicolchicines, namely -lumicolchicine 2, - lumicolchicine 3 and -lumicolchicine 4 that were also known as natural products and are formed by ring contrac- tion of the tropolone moiety (Scheme 1). As a part of a comprehensive study on the pharmaceutical properties of known and new colchicinoids, we investigated extensively the photochemical behavior of the non-nitrogen- containing 7-desacetamido-7-oxo-colchicine 5 (colchicone), a metabolite of colchicine (26), and 7-desacetamido-7-oxo- thiocolchicine 6 (thiocolchicone) (27,28) (Fig. 1). Our pur- pose was to indicate the possibility to obtain, as for colchi- cine, the corresponding lumoderivatives in order to evaluate their biological profile. In fact, the only known compound of this kind is -lumicolchicone 7 that was isolated several years ago (29) from tubers of Gloriosa superba L. in an enantiomerically pure form, as confirmed by its correlation to -lumicolchicine by oxidative deamination of the latter, whereas -lumicolchicone and the enantiomeric -lumicol- chicone were never isolated from natural sources. In our hands, irradiation of colchicone 5 afforded lumi- colchicone, whereas thiocolchicone 6 proved to be unreac- tive under the same experimental conditions. In order to ex- plore the reasons for this different behavior, we performed a full investigation of relationship between the structures of 5 and 6 and their reactivities, by means of time-resolved spectroscopy and semiempirical calculations, and herein we discuss the results of this effort. MATERIALS AND METHODS Photochemical reactions. Colchicone (10 mg) was dissolved in methanol (10 mL) and irradiated with a 125 W high-pressure mer- cury arc for 1 h. The solvent was evaporated and the crude product was chromatographed on silica gel. Elution with acetone—CH 2 Cl 2 1:9 gave pure lumicolchicone (8.5 mg, 85%). 1 H NMR (CDCl 3 ) : 6.61 (s, 1 H, aromatic proton), 6.54 (d, 1 H, J = 3 Hz, CH- CH=C[OCH 3 ]CO), 4.24 (dd, 1 H, J 1 = J 2 = 3 Hz, CH-CH-CH=), 4.05 (s, 3 H, MeO), 3.92 (s, 3 H, MeO), 3.90 (s, 3 H, MeO), 3.88 (m, 1 H, CH-CH-CH=), 3.70 (s, 3 H, MeO), 2.90 (m, 2 H, CH 2 - CH 2 ) and 2.65 ppm (m, 2 H, CH 2 -CH 2 ). This spectrum is identical to that of natural lumicolchicone. 13 C NMR (CDCl 3 ) : 196.98 (CO), 194.40 (CO), 158.22 (C=), 157.99 (C=), 155.54 (aromatic carbon), 153.23 (C[OMe]=), 140.72 (aromatic carbon), 139.86 (aromatic car- bon), 135.38 (aromatic carbon), 124.27 (aromatic carbon), 118.37