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After silylation of the imidazodiazepinone (X) employing bis(trimethylsilyl)trifluoroacetamide, glycosylation with 2-deoxy-3,5-di-p-toluoyl-D-erythro-pentofuranosyl chloride (XI) leads to a mixture of glycoside anomers (XII) and (XIII), from which the desired beta-anomer (XII) can be isolated by either column chromatography or by fractional crystallization. The toluoyl ester groups of (XII) are then removed by methanolysis in the presence of NaOMe to afford (XIV). Finally, reduction of ketone (XIV) gives rise to a 60:40 mixture of the target (R)-hydroxy imidazodiazepine along with its (S)-epimer (XV), which are separated by reverse-phase preparative HPLC

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Treatment of 5-methoxymethyluracil (I) with trimethylchlorosilane in the presence of triethylamine gives bis(trimethylsilyl)-5-methoxymethyluracil (II). Condensation of compound (II) with 3,5-di(0-p-toluoyl)-2-deoxy-D-ribofuranosyl chloride (III) yields an anomeric mixture of blocked nucleosides. The beta-anomer (IVa) is the major product and is purified by crystallization. After deblocking with hot sodium methoxide in methanol, 1-(2-deoxy-beta-D-ribofuranosyl)-5-methoxymethyluracil is obtained.

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The reaction of L-arabinose (I) with acetic anhydride and HBr gives tri-O-acetyl-b-L-arabinopyranosyl bromide (II), which is treated with Zn and Cu-Zn couple in aqueous AcOH to yield 3,4-di-O-acetyl-L-arabinal (III) (1). Reaction of compound (III) with HCl followed by treatment with refluxing methanol affords methyl 3,4-di-O-acetyl-2-deoxy-L-riboside (IV), which is deacetylated by means of NaOMe in methanol to provide methyl 2-deoxy-L-riboside (V). Reaction of riboside (V) with benzoic acid gives 2-deoxy-L-ribofuranose (VI), which, alternatively, can be obtained directly from diacetate (III) by treatment with aqueous HClO4 in AcOH/Ac2O. Reaction of ribofuranose (VI) with p-toluoyl chloride and methanol gives methyl 3,4-di-O-toluoyl-2-deoxy-L-riboside (VII), which is demethylated with HCl to yield 3,4-di-O-toluoyl-2-deoxy-L-ribose (VIII). Acylation of the ribose (VIII) with Ac2O and pyridine affords 1-O-acetyl-3,4-di-O-toluoyl-2-deoxy-L-ribose (IX), which is treated with HCl to provide the chloro-ribose (X). Condensation of compound (X) with thymine (XI) by means of HgCl2 and CdCO3 gives the acylated thymidine (XII), which is finally deacylated by treatment with NaOMe in methanol.

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2-Deoxy-L-ribose (VI) is converted into 1-chloro-1,2-dideoxy-3,5-di-O-p-toluoyl-L-ribose (X) by using Hoffer's method for the D-enantiomer. Treatment of 2-deoxy-L-ribose with MeOH in HCl/MeOH provides methyl 2-deoxy-L-riboside (XIII), which is condensed with p-toluoyl chloride by means of KHCO3 in pyridine to give methyl 2-deoxy-3,5-di-O-p-toluoyl-L-riboside (VII). Chlori-nation of riboside (VII) with glacial AcOH and HCl affords 1-chloro-1,2-dideoxy-3,5-di-O-p-toluoyl-L-ribose (X), which is condensed with 5-methyl-2,4-bis(trimethylsilyl-oxy)pyrimidine (XIV) by means of p-nitrophenol in chloroform to yield the protected thymidine (XII). Finally, this compound is deprotected by means of NH3 in methanol.

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