Synthesis and anti-HCV activity Of 2''-beta-hydroxymethylated nucleosides.

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

Synthesis of 2-C-hydroxymethylribofuranosylpurines as potent anti-hepatitis C virus (HCV) agents.

On the basis of potent anti-HCV activity of 2'-C-methyladenosine, novel 2'-C-hydroxymethyladenosine analogues 2a-c were synthesized from d-ribose in order to lead to favorable interaction with HCV polymerase. Among compounds tested, adenosine derivative 2a exhibited potent anti-HCV activity, indicating that the hydroxyl group of 2'-C-hydroxymethyl substituent led to favorable interaction with HCV polymerase.

Preparative and stereoselective synthesis of the versatile intermediate for carbocyclic nucleosides: effects of the bulky protecting groups to enforce facial selectivity.

The preparative and stereoselective synthesis (45-50% overall yields) of the target compound 17 has been accomplished from D-ribose. The bulky protecting groups such as TBDPS and Trityl enforced the facial selectivity during Grignard reaction to give the tertiary beta-allylic alcohol 16 as the sole product, which was oxidatively rearranged to the key molecule 17 in excellent yield.

Design, synthesis, and in vitro evaluation of APIO analogue of neplanocin A.

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.

Synthesis of apio analogues of neplanocin A as potential inhibitors of S-adenosylhomocysteine hydrolase.

Stereoselective synthesis of apio-neplanocin A and its related purine nucleosides which combined the properties of neplanocin A and apio nucleoside was achieved, starting from D-ribose via regioselective hydroxymethylation and ring-closing metathesis (RCM) as key steps. However, all synthesized compounds did not show significant inhibitory activity against S-adenosylhomocysteine hydrolase, unlike neplanocin A.