A New Strategy for the Asymmetric Synthesis of 1,3-Oxathiolane-Based Nucleoside Analogues

Abstract

A ready asymmetric synthesis of 3′‐oxathionucleosides has been accomplished in three main steps from benzoyloxyethanal. The synthesis is characterized by high overall yield and considerable enantiomeric excesses. It represents a general synthetic path to prepare a wide range of heterosubstituted sulfur‐containing nucleoside analogues.

Synthesis of Natural and Sugar-Modified Nucleosides Using the Iodine/Triethylsilane System as N-Glycosidation Promoter

“…To highlight the usefulness of the Et 3 SiH/I 2 reagent system in the synthesis of bioactive compounds, the method was eventually applied to improve the synthesis of the antiretroviral nucleoside apricitabine [ 57 , 58 ] ( Scheme 8 ). We first studied if the enantiomerically enriched [ 59 ] sulfoxide 17 could serve as a substrate for Et 3 SiH/I 2 N -glycosidation. However, after 1 h at −78 °C, the treatment of 17 with Et 3 SiH/I 2 only provided the corresponding sulfide.…”

Synthesis of β-l-2′-Fluoro-3′-thiacytidine (F-3TC) Stereoisomers: Toward a New Class of Oxathiolanyl Nucleosides?

“…In initial attempts, fluorine atom introduction was conceived at an early stage of the synthesis by an asymmetric, organocatalytic electrophilic fluorination of oxathiolanones 9a,b (Scheme 1 and Table 1). The latter were prepared starting from ethylene glycol 6 and glycerol 7 via aldehydes 8a,b as previously reported [22][23][24][25] (Scheme 1). The fluorination reaction was studied using L-proline as chiral organocatalyst; Selectfluor was chosen as the fluorine source in place of the more effective 26 N-fluorobenzenesulfonimide (NFSI), since use of the latter rapidly altered the starting oxathiolanones 9a,b (releasing the parent aldehydes 8a,b).…”

Chemical Synthesis of Heterocyclic−Sugar Nucleoside Analogues

“…Jin et al 120 Palumbo et al 121 accomplished a ready asymmetric synthesis of oxathionucleosides in 3 steps from benzoyloxyethanal. The key step was the asymmetric synthesis of sulfoxide 284, which was transformed into nucleosides 285 and 286 by condensation with the base in the presence of trimethylsilyl triflate and further deprotection with sodium methoxide (Scheme 76).…”