Adenosine mediated photoreaction with psoralen derivatives

Abstract

The adenine moiety mediated photoreaction of 4,5``,8-trimethylpsoralen (TMP) with adenosine or alcohol was investigated in a dry film state. Four TMP-ethanol photoadducts (I-IV), two TMP-methanol photoadducts (V-VI) and one minor TMP-adenosine Photoadduct (A) were isolated and purified by reverse phase liquid chromatography. The structures of photoproducts were elucidated by spectroscopic methods including UV, FT-IR, mass spectrometry (FAB, EI and HR methods) and $^1H$-NMR analysis. Covalent bond was formed between the 4-carbon of TMP and theribose 4``-carbon of adenosine photoproduct A in contrast to previously reported TMP-adenosine photoadducts. The lack of regiospecificity suggests a radical mechanism for these reactions. The UV absorption spectra and HPLC profiles show that photoproducts I and II(III and IV, V and VI) equilibrate at room temperature. The IV absorption maxima of protoproducts I(III and V) and II(IV and VI) at 257 and 248 nm, respectively, indicate that the pyrone ring is involved in the formation of photoproducts. The HR and EI mass spectra exhibit molecular ion peak at m/z 274 for photoproducts I-IV and at m/z 260 for photoproducts V-VI, which corresponds to the expected mass of 1:1 TMP-ethanol adduct and TMP-methanol adduct, repectively. In $^1H$-NMR spectra of photoproducts I-IV, the upfield shifted 4-methyl resonances appeared as singlet signals. The resonance peaks for the alcohol moiety are shown as pairs of doublet and quartet in photoproducts I-IV, and as a pairs of doublets in photoproducts V and VI. These results indicate that the photobinding of TMP occurs to alcohols through covalent bond formation between 4-carbon of the pyrone ring of TMP and $\alpha$-carbons to the hydroxyl group of alcohols. The equilibrium between photoproduct I(III or V) and II(IV or VII) are established by a intramolecular transesterification. The TMP-alcohol photoadducts were formed only in the TMP film containing small amounts of alcohol and adenosine. ...