Efficient synthesis of S-adenosyl-L-homocysteine natural product analoguesand their use to elucidate the structural determinant for cofactor bindingof the DNA methyltransferase M center dot HhaI

5'-Acetylthio-5'-deoxy-2',3'-O-isopropylideneadenosine (8) was directly pre pared from commercially available 2',3'-O-isopropylideneadenosine (7) and t hioacetic acid under Mitsunobu conditions in almost quantitative yield. In situ cleavage of the acetylthio function of 8 followed by coupling with dif ferent alkyl bromides proceeded with high yields. Deprotection of the obtai ned 5'-thionucleosides yielded the S-adenosyl-L-homocysteine analogues deca rboxylated AdoHcy (11), deaminated AdoHcy (14) and 5'-[3-(cyano)propylthio] -5'-deoxyadenosine (16) in good overall yields. Direct deprotection of the thionucleoside 8 delivered 5'-thio-5'-deoxyadenosine (18) in excellent yiel d. In addition, binding constants of these AdoHcy analogues and the DNA met hyltransferase M . HhaI were determined in fluorescence assay.