Yoshiko Sato

Deamination of 9-(Hydroxymethylated cycloalkyl)-9H-adenines (Carbocyclic Adenine Nucleosides) by Adenosine Deaminase: Effect of High-Pressure Upon Deamination Rate and Enantioselectivity 1) #

Abstract The deamination of eight kinds of racemic carbocyclic adenine nucleosides by adenosine deaminase under high-pressure (400 MPa) was examined and the result was compared with that obtained from the reaction under atmospheric pressure. The deamination of all carbocyclic nucleosides irrespective to their ring size of carbocycles was facilitated remarkably high-pressure. The reaction of three and five membered carbocyclic nucleosides resulted in the very high enantioselectivity both under high- and atmospheric Plessure whereas the enantioselectivity of six membered carbocyclic nucleosides was suppressed under high-pressure. However, the enantioselectivity of four membered nucleosides was low under both conditions. 1. Part 38 in the series “Synthesis of Nucleosides and Related Compounds”. For Part 37, see Katagiri, N.; Makino, S.; Kaneko, C. Chem. Pharm. Bid., 1995, 43, 884. #This paper is dedicated to the celebration of the 75th birthday of Dr. Yoshihisa Mizuno, Emeritus Professor of Hokkaido University.

Synthesis of uracil-5- and adenine-8-phosphonic acids

Abstract Successive treatments of 5-bromo-2,4-dimethyoxypyrimidine (I) with n-butyllithium and diethyl chlorophosphonate followed by dealkylation afforded uracil-5-phosphonic acid (V). Adenine-8-phosphonic acid (IX) was also prepared by a similar method, starting from 6-chloro-9-(tetrahdyro-2-pyranyl)purine (VI).

Synthesis of 8-Substituted Analogs of 3′-Deoxy-3′-fluoroadenosine1)

Abstract After 2′,5′-di-O-protection of 8-bromoadenosine, the product was converted to the xyloside, which was successively treated with diethylaminosulfur trifluoride (DAST) and acid to afford 8-bromo-3′-deoxy-3′-fluoroadenosine. 8-Mercapto and 8-oxy analogs were obtained from 8-bromo congener.

Synthesis and anti-HIV activity of 6-substituted purine 2'-deoxy-2'-fluororibosides

Abstract 3′,5′-Di-O-protected 6-chloropurine arabinoside 4b was treated with diethylaminosulfur trifluoride (DAST) and subsequently deprotected with pyridinium p-toluenesulfonate to give 6-chloropurine 2′-deoxy-2′-fluororiboside 6a. The displacement with nucleophile afforded the 6-substituted congener 6b-e. Treatment of 5′-O-protected 6-chloropurine arabinoside 3c with DAST gave lyxoepoxide 7.

Synthesis of Methylenecyclobutyl- and Cyclobutenyl Adenine, Potent Antiviral Carbocyclic Analogues of Oxetanocin A

9-Cyclobutyladenines bearing both methylene and hydroxymethyl groups, 3 and 4, were prepared by dehydration of carbocyclic oxetanocin A, 1a. Introduction of a double bond into cyclobutane ring was achieved by allylic oxidation of 12, which after several steps, afforded 5.

Synthesis and Anti-HIV Activity of 2-Substituted 2′-Deoxy-2′-fluoroadenosines

Abstract 2-Iodo-6-methoxypurine 2′-deoxy-2′-fluororiboside 8 was prepared from 2-iodo-6-methoxypurine riboside 1 in 8 steps. Reaction of 8 with ammonia in methanol gave the 2-iodoadenosine derivative 9 in 69% yield. Treatment of 9 with various nucleophiles gave 2-substituted analogues of 2′-deoxy-2′-fluoroadenosine 10–12. 2′-Deoxy-2,2′-difluoroadenosine 14 was also prepared by the treatment of the quaternary salt 13 with fluoride ion, but similar reactions of 13 with chloride or bromide ion gave the corresponding piperidine congeners 15a, b.