Preparation of 2′-Deoxy-2′-spirocyclopropylcytidine via an Alternative Cyclopropanation Reaction

Abstract

Herein we report the preparation of 2′-deoxy-2′-spirocyclopropylcytidine via an alternative cyclopropanation reaction starting from γ-silyl tertiary alcohols. Activation of the hydroxyl function with thionyl chloride in the presence of 4-DMAP allows the ring-closing step under mild conditions. Participation of the uracil moiety in the cyclization step is proposed.

Photoredox-Catalyzed Stereoselective Radical Reactions to Synthesize Nucleoside Analogues with a C2′-Stereogenic All-Carbon Quaternary Center

“…We have also explored the radical vinyl transfer on cyclic lactones ( 8 , Scheme b) prepared from the same Mukaiyama adducts to achieve the synthesis of analogues of type 3 . Our strategy provides an efficient access to highly functionalized α-substituted butyrolactones that complements other approaches for nucleoside synthesis. − …”

“…3 (hexanes/EtOAc, 70:30); formula C 22 H 22 O 6 ; MW 382.41 g/mol; IR (neat) ν max : 3457, 3065, 2968, 1717 cm −1 ; 1 H NMR (500 MHz, CDCl 3 ): δ 8.11−7.98 (m, 8H), 7.63−7.48 (m, 4H), 7.46 (td, J = 7.7, 4.8 Hz, 4H),7.39 (dt, J = 15.4, 7.7 Hz, 4H), 6.17 (dd, J = 17.6, 10.9 Hz, 1H, major), 5.96 (dd, J = 17.6, 10.9 Hz, 1H, minor), 5.79 (d, J = 6.7 Hz, 1H, major), 5.38−5.17(m, 5H), 5.10 (d, J = 3.2 Hz, 1H), 4.72−4.67 (m, 3H), 4.67 (d, J = 3.8 Hz, 1H, minor), 4.61 (dt, J = 6.2, 4.0 Hz, 1H, minor), 4.52 (dd, J = 11.4, 6.3 Hz, 1H, minor), 4.48−4.…”

Diastereoselective Synthesis of Arabino- and Ribo-like Nucleoside Analogues Bearing a Stereogenic C3′ All-Carbon Quaternary Center

“…5−7 This quaternary center is thought to enhance target specificity by preventing binding to enzymes or receptors susceptible to steric hindrance at this position. 8,9 Providing a versatile and straightforward methodology that extends the chemical space in this family of compounds would be useful in the field of medicinal chemistry. In this context, both arabinoand ribo-like scaffolds (Scheme 1) were targeted along with the syntheses of not only the β-anomers (1 and 3) but also the αanomers (2 and 4).…”

“…Nucleoside analogues are one of the most important families of drugs. , Our laboratory has been involved in the development of stereoselective acyclic free-radical-based transformations , toward the synthesis of therapeutic agents, such as novel nucleoside scaffolds bearing all-carbon stereogenic centers at C3′. − This quaternary center is thought to enhance target specificity by preventing binding to enzymes or receptors susceptible to steric hindrance at this position. , Providing a versatile and straightforward methodology that extends the chemical space in this family of compounds would be useful in the field of medicinal chemistry. In this context, both arabino- and ribo-like scaffolds (Scheme ) were targeted along with the syntheses of not only the β-anomers ( 1 and 3 ) but also the α-anomers ( 2 and 4 ).…”