Acta Chim. Slov. 2005, 52, 455–459 455 Scientific Paper Sensitized Photooxygenation of Tinosponone, a Clerodane Diterpene from Tinospora Cordifolia Jawaid Iqbal,* Adil Husain, and Anamika Gupta Department of Chemistry, Organic Chemistry Section, Aligarh Muslim University, Aligarh-202002 (U.P. ) India. E-mail: jawaid.iqbal0@lycos.com Received 02-04-2005 Abstract The reaction of tinosponone (1) with singlet oxygen was studied by using different combinations of photosensitizers (i.e. rose bengal, methylene blue, riboflavin and benzophenone), solvents (i.e. benzene, chloroform, acetone, acetonitrile and methanol) and singlet oxygen scavengers (i.e. DABCO and sodium azide). Two major products (3S,4aS,4bS,8R,8aR,10aR)-8-Hydroxy-3-(5'-hydroxy-2'-oxo-2',5'-dihydrofuran-3'-yl)-4a,8a-dimethyl-3,4,8,8a,9,10-hexahydro-10aH-benzo[f]isochromene-1,5(4aH,4bH)-dione (2) and (3S,4aS,4bS,8R,8aR,10aR)-8-Hydroxy-4a,8a-dimethyl-3-((1'R)-3'-oxo-4',6'-dioxa-bicyclo[3.1.0]hexan-1'-yl)-3,4,8,8a,9,10-hexahydro-10aH-benzo[f]isochromene-1,5(4aH,4bH)-dione (3) were isolated in all the solvents except methanol. In methanol a single product (3S,4aS,4bS,8R,8aR,10aR)-8-Hydroxy-3-(5'-hydroperoxy-2'-methoxy-2',5'-dihydrofuran-3'-yl)-4a,8a-dimethyl-3,4,8,8a,9,10-hexahydro-10aH-benzo[f]isochromene-1,5(4aH,4bH)-dione (4) was obtained. All products were characterized on the basis of IR, 1H NMR, 13C NMR and elemental analysis studies. The formation of products was explained by photooxidation of tinosponone. Effects of different solvents with the variation of added singlet oxygen sensitizers and singlet oxygen scavangers were observed on the yield of photooxidation products and were correlated to the rate of singlet oxygen formation. Key words: photooxygenation, tinosponone, clerodane diterpene, Tinospora cordifolia, benzo[f]isochromene Introduction The photoreactivity of synthetic drugs have been intensively studied in the recent past for their phototoxicity and phototherapeutic value.1,2 In contrast photochemical studies on biologically active natural products are very limited. Plant materials are well known for their biological activity and medicinal values.3–5 Hence it is of importance to study the photoreactivity of biologically active plant metabolites for a correlation to their possible in vivo photoreactions and phototoxicity. The photochemical study is expected to through light on improving the stability of these compounds in medicinal formulations derived from natural plant extracts. Within the context we have investigated the photooxidation of tinosponone (1), a clerodane diterpene isolated from Tinospora cordifolia. T. cordifolia is a plant of recognized medicinal values and is widely used as anti-bacterial, analgesic, antipyretic and also for the treatment of jaundice, skin diseases, diabetes, anemia etc.6–10 Several compounds containing 3-substituted furan moiety have been isolated from this plant species.11–13 In spite of immense medicinal use of this plant extract the photochemical sensitivity of their bioactive constituents has not been described in the literature. The 3-substituted furan moiety is quite susceptible to attack by biological oxygens; we therefore, have investigated photooxygenation of tinosponone under different combinations of sensitizer dyes and solvents. Results and discussion Irradiation of air-saturated benzene solution of tinosponone with methylene blue as sensitizer in a water-cooled immersion well type photoreactor equipped with medium pressure mercury vapour lamp and purification of the crude product by silica gel column chromatography afforded two compound 2 and 3. When tinosponone was irradiated with methylene blue in methanol, the chromatographic analysis (TLC) of irradiated mixture did not show the presence of any of the previously identified products (2 and 3), rather a new product 4 was observed (Scheme 1). When these photoreactions were carried out in the absence of sensitizer same products were obtained but the reaction was observed to be slow. The effect of nature of solvent on photooxidation was studied by using different solvents. The amount of substrate could not be kept same, as the solubility of substrate was different in different solvents. Therefore, relative yield of products was determined in these Iqbal et al. Sensitized Photooxygenation of Tinosponone 456 Acta Chim. Slov. 2005, 52, 455–459 cases. For this purpose, different reaction mixtures were irradiated under standard conditions for the same time period. Then 15 ml of each solution was taken out, concentrated and subjected to preparative TLC for the isolation of the products, and correlation of their yields. Yields of products in different solvents were found to vary with the polarity of the solvent. The yield was higher in polar solvents in comparison to non-polar solvents (Table 1). This observation may be attributed to longer lifetime of 1O2 in polar solvents.14,15 Owing to the solubility problem, the concentration of 1 was not same in all the solutions, as it was of methylene blue therefore, the possibility of energy transfer for different yields of products cannot be discarded. To confirm whether energy transfer or longer lifetime of 1O2 is responsible for different yields of products, we conducted experiments by varying the concentration of sensitizer (5Χ10-3-2Χ10-2 mol L-1) to the concentration of tinosponone in different solvents. Similar product patterns were obtained in these cases also, which supports the fact that lifetime of 1O2 and in turn polarity of solvent is responsible for the observed difference in the yields. HOO 4' Hi, o v 6 4bf I7 1 \ v A V' "OCH3 ^< 2 H