Tadashi Kataoka

Synthesis of carbocyclic pyrimidine nucleosides and their inhibitory activities against Plasmodium falciparum thymidylate kinase

Plasmodium falciparum thymidylate kinase (PfTMK) is a promising antimalarial target due to its unique substrate specificity. Recently, we reported that 2,3-dideoxycarbocyclic thymidine showed moderate inhibitory activity and reported the related structure-activity relationship for inhibitors against PfTMK. In this study, we have designed and synthesized enantioselective 2,3-dideoxycarbocyclic pyrimidine nucleosides based on our previous results and screened them for inhibitory activity against PfTMK. The most potent inhibitor showed K(i)(TMP) and K(i)(dGMP) values of 14 and 20 μM, respectively. The fluorinated dideoxy derivative (-)-7, exhibited lower K(i)(TMP) and higher K(i)(dGMP) compared with that of the parent compound (K(i)(TMP), K(i)(dGMP) equals 20 and 7 μM, respectively). The modification of carbocyclic pyrimidine nucleosides is a promising strategy for developing powerful PfTMK inhibitors.

A convenient synthesis of alkynylpyrazoles

Diazomethane add to the enyne sulfones 1, 3, 4, 6–11 regio- nand stereo-selectively to give the n4-alkynyl-5-phenylsulfonyl-4,5-dihydro-3H-pyrazoles 12–15 nand 17–19, which are converted by MeLi into the n4-alkynyl-1H-pyrazoles 24, 25, 16, 26, 28, 30 in good yields. n4,5-Bis(alkynyl)-1H-pyrazoles 34, 37 are also obtained by the nsame procedure.

NOVEL CONSTRUCTION OF 5-METHYLENEPYRROL-2-ONES BY INTRAMOLECULAR CYCLIZATION OF SELENIUM-STABILIZED ALKYNYL AMIDES

(Z)-5-(Phenylselenomethylene)pyrrol-2-ones 18–22 have been obtained in good yields from the cyclization of ω-seleno-substituted alkynyl amides 11–15 with ButOK–18-crown-6.