ABSTRACT
A total synthesis of apio-neplanocin A, which combines properties of apio nucleoside and neplanocin A and is a potential inhibitor of S-adenosylhomocysteine hydrolase, was accomplished starting from D-ribose via stereoselective hydroxymethylation and RCM reaction. [reaction: see text]
Subject(s)
Adenosine/analogs & derivatives , Adenosine/chemistry , Adenosine/chemical synthesis , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/chemical synthesis , Hydrolases/antagonists & inhibitors , Adenosylhomocysteinase , Molecular Structure , StereoisomerismABSTRACT
Pyrimidine nucleosides fused with 3',4'-tetrahydrofuran ring were synthesized, starting from 1,2;5,6-di-O-isopropylidene-D-glucose and assayed for antiviral activities. Thymine analogue 1 and its corresponding 2'-deoxy analogue 3 exhibited high cytotoxicity instead of giving antiviral activities.
Subject(s)
Furans , Pyrimidine Nucleosides/chemical synthesis , Indicators and Reagents , Models, Molecular , Pyrimidine Nucleosides/chemistryABSTRACT
The bicyclic 3'-O,5'-C-methylene-linked and 2'-O,5'-C-methylene-linked 5-azacytidine derivatives were readily synthesized from 1,2;5,6-di-O-isopropylidene-D-glucose and evaluated against several cancer cell lines.
Subject(s)
Antineoplastic Agents/chemical synthesis , Azacitidine/analogs & derivatives , Azacitidine/chemical synthesis , Antineoplastic Agents/chemistry , Azacitidine/chemistry , Cell Survival/drug effects , Drug Screening Assays, Antitumor , Humans , Indicators and Reagents , Molecular Structure , Tumor Cells, CulturedABSTRACT
In view of biological activities of azole nucleosides and apio-dideoxynucleoside, novel apio nucleoside analogues (1 and 2) with thiazole and triazole base moiety were synthesized using 2,3-O-isopropylidene-apio-beta-D-furanose (3), which was prepared from D-mannose.
Subject(s)
Mannose/analogs & derivatives , Nucleosides/chemical synthesis , Thiazoles/chemical synthesis , Triazoles/chemical synthesis , Mannose/chemistry , Nucleosides/chemistry , Structure-Activity Relationship , Thiazoles/chemistry , Triazoles/chemistryABSTRACT
Halogenated analogues of neplanocin A were synthesized from the key intermediate 1, among which fluoro-neplanocin A was found to be novel mechanism-based irreversible inhibitor of S-Adenosylhomocysteine hydrolase.
Subject(s)
Adenosine/chemical synthesis , Adenosylhomocysteinase/adverse effects , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacology , Adenosine/analogs & derivatives , Adenosine/chemistry , Adenosine/pharmacology , Indicators and Reagents , Kinetics , Models, Molecular , Molecular ConformationABSTRACT
A novel apio analogue of neplanocin A was efficiently synthesized from D-ribose via stereoselective aldol-retroaldol reaction for introducing hydroxymethyl group and RCM reaction for synthesizing carbocycle, and its inhibitory activity against SAH hydrolase was assayed.
Subject(s)
Adenosine/chemical synthesis , Adenosylhomocysteinase/antagonists & inhibitors , Enzyme Inhibitors/chemical synthesis , Adenosine/analogs & derivatives , Adenosine/chemistry , Adenosine/pharmacology , Drug Design , Indicators and Reagents , Molecular Structure , Structure-Activity RelationshipABSTRACT
The pyrimidine nucleosides fused with 3',4'-tetrahydrofuran ring were successfully synthesized, starting from 1,2;5,6-di-O-isopropylidene-D-glucose and assayed for antiviral activities against HIV-1, HIV-2, EMCV, Cox. B3 and VSV. Thymine analogue (5) and its corresponding 2'-deoxy analogue (6) exhibited high cytotoxicity instead of giving antiviral activities.
Subject(s)
Furans/chemistry , Thymine/chemical synthesis , Thymine/pharmacology , Cell Line , Microbial Sensitivity Tests , Thymine/chemistry , Viruses/drug effectsABSTRACT
Several 3'-fluoro analogues, 1a, 1b, and 1c of selective and potent adenosine A(3) receptor agonist, Cl-IB-MECA were synthesized from D-xylose via highly regioselective opening of lyxo-epoxides, 8a and 8b with fluoride anion. Compared to the high binding affinity of Cl-IB-MECA to the A(3) adenosine receptor, the corresponding 3'-fluoro derivative showed remarkably decreased binding affinity, indicating that 3'-hydroxyl group acts as hydrogen bonding acceptor, not hydrogen bonding donor like fluorine atom in binding to the A(3) adenosine receptor.