Satoshi Yaginuma

STUDIES ON NEPLANOCIN A, NEW ANTITUMOR ANTIBIOTIC. I

Neplanocin A. C11H13N5O3, is a novel carbocyclic analog of adenosine with cyclopentene. It was isolated from the culture filtrate of Ampullariella regularis A11079 by means of ion-exchange, carbon, silica gel adsorption, or partition chromatography. Neplanocin A forms crystals, and is stable at acidic or alkaline pH. Neplanocin A has cytotoxicity against L5178Y cells in culture and showed a remarkable effect on the life prolongation of mice infected with L1210 leukemia.

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.

The Structure of Neplanocin C

Abstract The molecular and crystal structure of neplanocin C(3), C11H13N5O4 M.W. = 279.26, has been determined by X-ray anlysĩs. The space group is P21 with a=16.381(2), b=8.210(1), c=9.127(1) A, β=105.31(1)° and z=4. The structure was solved by direct method, and least-squares refinement using 2093 reflections with |Fo|>3σ(F) led to the final R value of 0.0772. The sugar puckering of the two crystal-lographically independent molecules is C(2′)-exo-C(3′)-endo, and the torsion angles about the N(9)-C(1′) bond are 22.8(6) and 28.7(6)°, respectively (anti conformation).

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.