Development of the Efficient Synthetic Method for Nucleosides labeled with Stable Isotopes and Their Application to Structural Analysis of the Complex of a DNA with a Drug

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For the elucidation of the recognition mechanism of a DNA with a drug, the studies were performed as follows ; 1. the structural analysis of the complex of a [5'-^<13>C]DNA with Tallimustine (distamycin analogue) by NMR spectroscopy and 2. the development of the efficient methodology for the synthesis of 2'-deoxyribonucleosides site-specifically and diastereoselectivly labeled with ^<13>C and/or ^2H at their 5'- or 3'-positions. On the first study, the analysis of a d(C^*G^*C^*G^*A^*A^*T^*T^*C^*G^*C^*G)_2 {N^* : [5'-^<13>C]nucleotide} provided us with the correlation between C5'(i)-C6H(i-1) or -C8H(i), the sequential NOEs and unambiguous assignment of all the signals. We extend these results to NMR study of the complex of [5'-^<13>C]DNA with Tallimustine (distamycin analogue). The structural information on surrounded by H5' protons in a complex of these drug with a DNA has not been obtained, because of the difficulty of the assignment for H5' proton signals. We have overcome this problem by NMR analysis of a complex of [5'-^<13>C]DNA with a drug. Information obtained from our studies should aid in the investigation of sequence-specific DNA-protein or -drug recognition processes.On the second studies, we achieved the development of the efficient methodology for the synthesis of (2'R)-2'-deoxy[2-^2H]guanosine and D-[5-^2H]ribofuranose derivative. Moreover, we found that a significant role of the phenylcarbamoyl protecting group in the asymmetric dihydroxylation reaction of the unsubstituted allyl alcoholic system using AD-mix-α and -β was confirmed to afford remarkably high enantioselectivity (>99% ee).