The title compound was prepared starting from the known menthyl 5(S)-acetoxy-1,3-oxathiolan-2(R)-carboxylate (I). Transposition of the 5-acetoxy group of (I) to the target 4-acetoxy derivative (VI) was achieved by the following sequence. The acetoxy group of (I) was first removed by reduction with triethylsilaneto give (II), followed by ester reduction with NaBH4, to give the hydroxymethyl oxathiolane (III). The primary alcohol of (III) was then protected by silylation with tert-butyldiphenylsilyl chloride. The resultant silylated oxathiolane (IV) was oxidized to a diastereomeric mixture of sulfoxides (V) using m-CPBA. Pummerer rearrangement of sulfoxides (V) in the presence of Ac2O and Bu4NOAc furnished the desired 4-acetoxy thiolane (VI). Glycosylation of (VI) with N-acetylcytosine (VII) in the presence of trimethylsilyl triflate provided a mixture of cis- and trans-coupled products, which were separated by preparative TLC. The required cis-isomer (VIII) was desilylated with tetrabutylammonium fluoride, followed by acetamide hydrolysis with K2CO3 in MeOH, to provide the title compound.

The title compound was prepared starting from the known menthyl 5(S)-acetoxy-1,3-oxathiolan-2(R)-carboxylate (I). Transposition of the 5-acetoxy group of (I) to the target 4-acetoxy derivative (VI) was achieved by the following sequence. The acetoxy group of (I) was first removed by reduction with triethylsilaneto give (II), followed by ester reduction with NaBH4, to give the hydroxymethyl oxathiolane (III). The primary alcohol of (III) was then protected by silylation with tert-butyldiphenylsilyl chloride. The resultant silylated oxathiolane (IV) was oxidized to a diastereomeric mixture of sulfoxides (V) using m-CPBA. Pummerer rearrangement of sulfoxides (V) in the presence of Ac2O and Bu4NOAc furnished the desired 4-acetoxy thiolane (VI). Glycosylation of (VI) with N-acetylcytosine (VII) in the presence of trimethylsilyl triflate provided a mixture of cis- and trans-coupled products, which were separated by preparative TLC. The required cis-isomer (VIII) was desilylated with tetrabutylammonium fluoride, followed by acetamide hydrolysis with K2CO3 in MeOH, to provide the title compound.

The title compound was prepared starting from the known menthyl 5(S)-acetoxy-1,3-oxathiolan-2(R)-carboxylate (I). Transposition of the 5-acetoxy group of (I) to the target 4-acetoxy derivative (VI) was achieved by the following sequence. The acetoxy group of (I) was first removed by reduction with triethylsilaneto give (II), followed by ester reduction with NaBH4, to give the hydroxymethyl oxathiolane (III). The primary alcohol of (III) was then protected by silylation with tert-butyldiphenylsilyl chloride. The resultant silylated oxathiolane (IV) was oxidized to a diastereomeric mixture of sulfoxides (V) using m-CPBA. Pummerer rearrangement of sulfoxides (V) in the presence of Ac2O and Bu4NOAc furnished the desired 4-acetoxy thiolane (VI). Glycosylation of (VI) with N-acetylcytosine (VII) in the presence of trimethylsilyl triflate provided a mixture of cis- and trans-coupled products, which were separated by preparative TLC. The required cis-isomer (VIII) was desilylated with tetrabutylammonium fluoride, followed by acetamide hydrolysis with K2CO3 in MeOH, to provide the title compound.

The title compound was prepared starting from the known menthyl 5(S)-acetoxy-1,3-oxathiolan-2(R)-carboxylate (I). Transposition of the 5-acetoxy group of (I) to the target 4-acetoxy derivative (VI) was achieved by the following sequence. The acetoxy group of (I) was first removed by reduction with triethylsilaneto give (II), followed by ester reduction with NaBH4, to give the hydroxymethyl oxathiolane (III). The primary alcohol of (III) was then protected by silylation with tert-butyldiphenylsilyl chloride. The resultant silylated oxathiolane (IV) was oxidized to a diastereomeric mixture of sulfoxides (V) using m-CPBA. Pummerer rearrangement of sulfoxides (V) in the presence of Ac2O and Bu4NOAc furnished the desired 4-acetoxy thiolane (VI). Glycosylation of (VI) with N-acetylcytosine (VII) in the presence of trimethylsilyl triflate provided a mixture of cis- and trans-coupled products, which were separated by preparative TLC. The required cis-isomer (VIII) was desilylated with tetrabutylammonium fluoride, followed by acetamide hydrolysis with K2CO3 in MeOH, to provide the title compound.

A new asymmetric synthesis has been reported. Oxidative cleavage of mono-benzoyl glycerol (IX) by means of NaIO4 provided aldehyde (X). Condensation of (X) with mercaptoethanol (XI) in the presence of ploystyryl diphenylphosphane-iodine complex gave rise to the oxathiolane (XII). Sharpless asymmetric oxidation of (XII) using tert-butyl hydroperoxide and L-diethyl tartrate led to an 82:18 mixture of (E)- and (Z)-sulfoxides (XIII) and (XIV). The desired (E)-isomer (XIII) was then isolated by column chromatography, displaying an enantiomeric excess of 60%. Coupling of (XIII) with N-acetylcytosine (VII) under Pummerer rearrangement conditions led to an equimolecular mixture of (Z)- and (E)-adducts (XV) and (XVI). After chromatographic separation of the desired (Z)-isomer (XV), the acetyl and benzoyl protecting groups were removed by treatment with sodium methoxide.