Kang Man Lee

Synthesis and Biological Evaluation of Halo-neplanocin A as Novel Mechanism-Based Inhibitors of S-Adenosylhomocysteine Hydrolase

Abstract 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.

Truncated Fluorocyclopentenyl Pyrimidines as S-Adenosylhomocysteine Hydrolase Inhibitors

On the basis of inhibitory activity of truncated cyclopentenyl cytosine against S-adenosylhomocysteine hydrolase (SAH), its fluorocyclopentenyl pyrimidine derivatives were efficiently synthesized from D-ribose via electrophilic fluorination as a key step. The final nucleosides were evaluated for SAH inhibitory activity, among which the uracil derivative 9 showed significant inhibitory activity (IC50 = 8.53 μM). They were also evaluated for cytotoxic effects in several human cancer cell lines such as fibro sarcoma, stomach cancer, leukemia, and colon cancer, but they did not show any cytotoxic effects up to 100 μM, indicating that 4′-hydroxymethyl groups are essential for the anticancer activity.

Structure-activity relationship of 5'-substituted fluoro-neplanocin a analogues as potent inhibitors of S-adenosylhomocysteine hydrolase.

Four 5′-substituted fluoro-neplanocin A analogues 1a–d were designed and synthesized, and the inhibitory activity against SAH was in the following order: NH2 > SH > F, N3, indicating a hydrogen bonding donor is essential for inhibitory activity.

Asymmetric Synthesis of Novel Apio Carbocyclic Nucleoside Analogues as Potential Antiviral and Antitumor Agent

Novel apio carbocyclic nucleosides 18–21 were asymmetrically synthesized as potential antiviral and antitumor agent, starting from D-ribose employing aldol reaction, RCM reaction and Mitsunobu reaction as key reactions.

Asymmetric Synthesis of Cyclopropyl-fused 2′- C -Methylcarbanucleosides as Potential Anti-HCV Agents

Novel 2 ′-C-methyl-cyclopropyl-fused carbocyclic nucleosides as potential anti-HCV agents were stereoselectively synthesized, utilizing regioselective cleavage of the isopropylidene group and cyclic sulfate chemistry as key steps.

Synthesis And Anti-Hcv Activity Of 2″-β-Hydroxymethylated Nucleosides

Synthesis of 2′ -β-hydroxymethyl nucleosides 3–6 was accomplished, using stereoselective hydroxymethylation as a key step. Adenine nucleoside 3 showed potent anti-HCV activity, implying that 2′ -β-hydroxymethyl group has the appropriate electronic properties interfering with HCV polymerase.

Synthesis of halogenated 9-(dihydroxycyclopent-4'-enyl) adenines and their inhibitory activities against S-adenosylhomocysteine hydrolase.

Abstract Novel halovinyl analogues of neplanocin A without 4′-hydroxymethyl group were easily synthesized starting from d-ribose via cyclopentenone 5 as a key intermediate and their inhibitory activity against SAH hydrolase was assayed.

Stereoselective Synthesis Of Homo-Apioneplanocin A As Potential Inhibitor Of S-Adenosylhomocysteine Hydrolase

Homo-apioneplanocin A (1) as a potential inhibitor of S-adenosylhomocysteine hydrolase was synthesized from D-ribose, employing stereoselective hydroxymethylation, regioselective oxidation, and regio- and chemoselective hydroboration as key steps.

STEREOSELECTIVE SYNTHESIS OF 3-HYDROXYMETHYL-D-CYCLOPENTENONE, THE VERSATILE INTERMEDIATE FOR THE SYNTHESIS OF CARBOCYCLIC NUCLEOSIDES

The preparative and stereoselective synthesis (45–50% overall yields, >50 g scale) of the key carbasugars 7a–d was achieved from D-ribose via stereoselective Grignard reaction and oxidative rearrangement as key reactions.