For the first time, a series of novel 1 0 -homo-N-2 0 -deoxy-a-nucleosides containing natural nucleobases as well as 5-fluoro and 5-iodopyrimidine analogs have been synthesized in an efficient manner. Additionally, a high yield protocol for the assembly of a dimeric scaffold containing two sugar moieties linked to the N-1 and N-3 positions of a single pyrimidine base has been accomplished. The structures of the novel homonucleosides were established by a single crystal X-ray structure of 1 0 -homo-N-2 0 -deoxy-aadenosine and NMR studies. The biological activity of these 1 0 -homo-N-2 0 -deoxy-a-nucleosides as antiviral (HIV-1 and HBV) and cytotoxic studies was measured in multiple cell systems. The unique structure and easy accessibility of these compounds may allow their use in the design of new nucleoside analogs with potential biological activity and as a scaffold for combinatorial chemistry.

An enzymatic process was optimized for regioselective levulinylation of the 5′-hydroxyl group in 2′-deoxynucleosides. The results revealed that the nucleobase protecting group influenced the successful outcome of the enzymatic reaction. The enhanced solubility of 4-tert-butylphenoxyacetyl protected 2′-deoxynucleoside played a major role during acylation reaction enabling the starting nucleosides to be the best substrates for Candida antarctica lipase B. Furthermore, we have developed a packed column protocol as a superior alternative to batch process carried-out in a flask, particularly when scale-up is required. The industrial application of this method was demonstrated via the synthesis of 5′-O-levulinylthymidine on a 25 g scale.

The introduction of a novel thymine derivative at the 3′-end of the sense strand generates more potent and selective siRNAs.

Enantiopure (2R)-configuredn on-natural (À)-muscarine and (+ +)-allo-muscarine were efficiently synthesized by ac hemoenzymatic approach from an easily accessible cyano-sugar available on al arge-scale.T he key enzymatic hydrolysiss tep was accomplishedb yi mmobilized Burkholderiac epacia lipase (also known as Pseudomonas cepacia lipase, PSL-IM). TheP SL-IM-mediated regioselective hydrolysiso ft he 5-O-toluoyle ster group in a-a nd bcyano-sugars,f urnished 3-O-toluoyl-a-cyano-sugar and 3-O-toluoyl-b-cyano-sugar, respectively,w ith total selectivity and in excellent yields.T od emonstrate the industrial utility of this method, 3-O-toluo-yl-b-cyano-sugar was synthesized on a1 0g scale using PSL-IM andt he catalyst was reused.Akey feature of the synthesis route describedh erein is the simultaneous hydrogenolysis of at osyl group,r eduction of an itrilea nd deprotection of at oluoyl group using LiAlH 4 in ao ne-pot procedure.T his study offersagreenp rotocolf or synthesis of two muscarine derivatives in high yieldse mployingaconcise four-step strategy.