Takumi Obara

New neplanocin analogues. II: Enzymatic one-step synthesis and antitumor activity of 6'-(3-sn-phosphatidyl)neplanocin a derivatives

Abstract A novel series of neplanocin analogues, 6′-(3-sn-phosphatidyl)neplanocin As bearing a variety of fatty acyl or alkyl residues in the glyceride moiety (2b-2h), were synthesized by means of phospholipase D-catalyzed transphosphatidylation. Among them, 2b, 2c, and 2e each exhibited significant antitumor effect against P388 leukemia in mice, which evidently surpassed that of parent compound neplanocin A.

New neplanocin analogues. III: 6'R-configuration is essential for the antiviral activity of 6'-C-methyl-3-deazaneplanocin A's

(6′ R )- and (6′ S -6′- C -methyl-3-deazaneplanocin As were synthesized from D-ribose as anti-RNA virus agents. Of these compounds, (6′ R )-6′- C -methyl-3-deazaneplanocin A ( 4b ) showed the greatest anti-RNA virus activity in vitro . It was found that the 6′ R -configuration was essential for the antiviral activity of 6′- C -methylneplanocin A derivatives.

New Neplanocin Analogues. V. A Potent Adenosylhomocysteine Hydrolase Inhibitor Lacking Antiviral Activity. Synthesis And Antiviral Activity Of 6″-Carboxylic Acid Derivatives Of Neplanocin A 1

Abstract The 6′-carboxylic acid derivative of neplanocin A 3 was synthesized from NPA, and was converted to the corresponding methyl ester 4 and amides 5 and 6. These were evaluated for their anti-RNA-virus activities. Of the derivatives synthesized, only 5 was active against RNA viruses within the concentration range of 0.14-4.88 μg/mL. Compounds 3 and 5 showed a potent inhibitory effect on S-adenosylhomocysteine (AdoHcy) hydrolase from rabbit erythrocytes. Although a close correlation between the inhibitory effect of adenosine analogues on AdoHcy hydrolase and their antiviral potency has been demonstrated, 3 did not show any anti-RNA-virus activities. 1This paper constitutes part 146 of Nucleosides and Nucleotides. Part 145. Shuto, S.; Haramuishi, K.; Matsuda, A. Tetrahedron Lett. Submitted.