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Synthesis and Properties of New Nucleotide Analogues Possessing Squaramide Moieties as New Phosphate Isosters
Author(s) -
Seio Kohji,
Miyashita Takuhei,
Sato Kousuke,
Sekine Mitsuo
Publication year - 2005
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/ejoc.200500520
Subject(s) - squaramide , chemistry , nucleotide , moiety , stereochemistry , bromide , phosphate , ribose , combinatorial chemistry , biochemistry , enantioselective synthesis , organic chemistry , organocatalysis , gene , enzyme , catalysis
New analogues of 2′‐deoxynucleotides and ribonucleotides incorporating a unique squaramide structure were synthesized. Because of the strong acidity of this moiety (p K a = 2.3), these nucleotide analogues exist in a monoanionic form, which can be regarded as an electronic isoster of 5′‐nucleotides under physiological conditions. The synthesis of the nucleotide analogues was achieved through the condensation of 5′‐ or 3′‐aminonucleosides with dimethyl squarate, whilst the selective removal of the methyl group was effectively accomplished by treatment with sodium bromide. In addition, we also synthesized 3′,5′‐cyclic nucleotide analogues from the 3′,5′‐diazidonucleoside derivatives. NMR analysis revealed that their ribose puckering was of an N‐type form, identical to that in cAMP and cGMP. Because of the unique structural, electronic, and conformational properties of squaramide‐type nucleotide analogues, these analogues should be quite interesting as potential biologically active compounds such as antiviral and anticancer agents. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)