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
M. Pignot et al., 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, EUR J ORG C, (3), 2000, pp. 549-555
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.