C. K. Chu

Determination of the Anomeric Configuration of C-Nucleosides by 1H and 13C NMR Spectroscopy

Abstract Since the discovery by Cohn in 1959 of the first C-nucleoside pseudouridine, an isolate from t-RNA hydrolysates, a number of biologically interesting C-nucleosides [formycin. formycin B. oxoformycin, oxazinomycin (minimycin), showdomycin, pyrazofurin, and several derivatives of pseudouridine] have been isolated from the culture filtrates of various micro-organisms, and their structures have been elucidated. Several review articles dealing with the chemistry and/or biology of C-nucleosides have appeared.

Troxacitabine Prodrugs for Pancreatic Cancer

Troxacitabine is a cytotoxic deoxycytidine analogue with an unnatural L-configuration, which is activated by deoxycytidine kinase (dCK). The configuration is responsible for differences in the uptake and metabolism of troxacitabine compared to other deoxynucleoside analogues. The main drawback in the use of most nucleoside anticancer agents originates from their hydrophilic nature, which property requires a high and frequent dosage for an intravenous administration. To overcome this problem several troxacitabine prodrugs modified in the aminogroup with a linear aliphatic chain with a higher lipophilicity were developed. To determine whether these prodrugs have an advantage over Troxacitabine pancreatic cancer cell lines were exposed to Troxacitabine and the lipophilic prodrugs. The addition of linear aliphatic chains to troxacitabine increased sensitivity of pancreatic cancer cell lines to the drug > 100-fold, possibly due to a better uptake and retention of the drug.

Beta-L-(-)-dioxolane Cytidine (β-L-(-)-OddC) as a Potent Compound for the Treatment of Cancer

Abstract L-(-)-OddC is the first nucleoside analog with the unnatural L-configuration and the first chain-terminator shown to have anti-cancer activity. This compound was found to be highly active against solid tumor growth in several human xenograft models. L-(-)-OddC exerts its activity be terminating DNA chain elongation after its incorporation.

The Crystal and Molecular Structure of the Complex of 2′3′-Didehydro-2′3′-Dideoxyguanosine with Pyridine

Abstract The structure of 2′,3′-didehydro-2′,3′-dideoxyguanosine was determined by X-ray crystallographic analysis of the complex with pyridine. The two independent nucleoside molecules have similar, commonly observed glycosyl link (x = -102.3° and -94.2°) and 5′-hydroxyl (y = 54.0° and 47.6°) conformations. The five-membered rings are very planar with r.m.s. deviations from planarity of less than 0.015 A. 2′,3′-Didehydro-2′,3′-dideoxyadenosine has a similar glycosyl link conformation but a different 5′-hydroxyl group orientation and a slightly less planar 5-membered ring.

Synthesis of 2′,3′-Dideoxy-2′-Fluoro-l-threo-Pentofuranosyl Nucleosides as Potential Antiviral Agents

A series of 2,3-dideoxy-2-fluoro-L-threo-pentofuranosyl nucleosides has been synthesized as potential antiviral agents. The synthesized compounds were evaluated against HIV-1, HBV, HSV-1, and HSV-2. Among the synthesized analogues, only the cytosine derivative showed moderate antiviral activity against HIV and HBV.

Practical synthesis of D-cyclopent-2-enone, the key intermediate of carbocyclic nucleosides

Abstract An efficient and practical method for the synthesis of (4R,5R)-4,5-O-isopropylidene-cyclopent-2-enone was developed from D-ribose by using a ring-closing metathesis reaction.

Acetylation of Nucleosides by Acetylsalicylic Acid (Aspirin)1

Abstract Acetylsalicylic acid (aspirin) reacted with adenosine, cytidine, guanosine and their 2′-deoxynucleosides to give acetylated nucleosides. Cytidine and 2′-deoxycytidine gave N4-acetylated nucleosides in nitromethane while in pyridine fully acetylated products were obtained. Adenosine and 2′-deoxyadenosine also gave fully acetylated products. However, guanosine and 2′-deoxyguanosine gave 2′,3′,5′-tri-O-acetylribosyl and 3′,5′-di-O-acetyl-2′-deoxyribosyl nucleosides, respectively. The corresponding aglycons also gave acetylated heterocycles under various conditions.