Identification and Structure Determination of a Third Cyclobutane Photodimer of Thymidylyl-(3′→5′)-thymidine: The trans-syn-II Product

Photolysis of thymidylyl-(3′→5′)-thymidine (TpT) has been previously reported by many workers to lead to only two cyclobutane dimers, the cis-syn and trans-syn-I dimers. This is curious in light of the fact that photolysis of thymidylyl-(3′→5′)-deoxyuridine (TpdU), which has a hydrogen in place of a methyl group at C6 of the 3′-thymidine, produces two trans-syn diastereomers. Recently, we discovered by way of X-ray crystallography that photolysis of the (R_p)-methyl phosphate ester of TpT leads to two trans-syn diastereomers, prompting us to reexamine the photochemistry of TpT. In this paper we show that sensitized photolysis of TpT also leads to the hitherto unknown trans-syn-II diastereomer in 2% yield. We also report the solution-state ¹H NMR assignment of the trans-syn-II photodimer of TpT and its (R_p)-methyl phosphate ester by way of 2D homonuclear Hartmann–Hahn experiment, rotating frame nuclear Overhauser effect spectroscopy, and proton-detected ¹H–³¹P correlation spectroscopy. Conformational analysis of three-bond ¹H–¹H, ¹H–³¹P, and ¹³C–³¹P coupling constant data established a close similarity between the solution-state structures of the trans-syn-II photodimer of TpT and its (R_p)-methyl phosphate ester, with the crystal structure of the methyl phosphate ester.