Premium
Efficient Synthesis of S ‐Adenosyl‐ L ‐Homocysteine Natural Product Analogues and Their Use to Elucidate the Structural Determinant for Cofactor Binding of the DNA Methyltransferase M· Hha I
Author(s) -
Pignot Marc,
Pljevaljcic Goran,
Weinhold Elmar
Publication year - 2000
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/(sici)1099-0690(200002)2000:3<549::aid-ejoc549>3.0.co;2-7
Subject(s) - chemistry , stereochemistry , methyltransferase , yield (engineering) , mitsunobu reaction , cleavage (geology) , dna , dna methyltransferase , cofactor , deoxyadenosine , alkyl , fluorescence , enzyme , organic chemistry , methylation , biochemistry , materials science , geotechnical engineering , fracture (geology) , engineering , metallurgy , physics , quantum mechanics
5′‐Acetylthio‐5′‐deoxy‐2′,3′‐ O ‐isopropylideneadenosine ( 8 ) was directly prepared from commercially available 2′,3′‐ O ‐isopropylideneadenosine ( 7 ) and thioacetic acid under Mitsunobu conditions in almost quantitative yield. In situ cleavage of the acetylthio function of 8 followed by coupling with different alkyl bromides proceeded with high yields. Deprotection of the obtained 5′‐thionucleosides yielded the S ‐adenosyl‐ L ‐homocysteine analogues decarboxylated 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 yield. In addition, binding constants of these AdoHcy analogues and the DNA methyltransferase M · Hha I were determined in a fluorescence assay.