Synthesis of Cyclobutane Nucleosides 2-Preparation of Thymine and Uracil Analogues

Abstract

1-(2-Oxocyclobutyl-4-benzoyloxymethyl)-2,4(1H,3H)-pyrimidinedione and 1-(2-oxocyclobutyl-4-benzoyloxymethyl)-5-methyl-2,4(1H,3H)-pyrimidinedione can be prepared by reaction of uracil and thymine, respectively, with 3-benzoyloxymethyl-2-bromocyclobutanone. The N-alkylation gave both cis and trans isomers with the trans isomer predominating for uracil whereas the trans isomer was the only product which could be isolated for thymine. Both series were subjected to borohydride reduction followed by transesterification with methoxide giving the corresponding uracil and thymine nucleoside analogues. The uracil derivative 1-(2-oxocyclobutyl-4-benzoyloxymethyl)-2,4(1H,3H)-pyrimidinedione was irradiated in aqueous acetonitrile to generate isonucleoside analogues.

Design, Synthesis, and Evaluation of Novel 2-Methoxyestradiol Derivatives as Apoptotic Inducers through an Intrinsic Apoptosis Pathway

“…In recent years, uridine, uracil, and thymine (2, 3, and 4, Figure 1) have attracted much interest due to their promising potential biological activities, and their modified derivatives have exhibited excellent activities, such as antibacterial, inhibition against 1,4-β-galactosyltransferase, antivirus, anticancer, and so on [29][30][31][32][33][34][35][36]. Our previous studies [37,38] have also shown that uridine/uracil/thymine attached to the natural compound oleanolic acid could afford derivatives that possess high anti-proliferative activities against tumor cell lines and exhibit clearly inducing effects on cell apoptosis.…”