Recent Advances in the Synthesis of Carbocyclic Nucleosides via Ring‐Closing Metathesis

Abstract

The past decades witnessed the development and the strong potential of nucleoside analogues as therapeutic agents as well as biological tools. Among this, five‐membered carbocyclic nucleosides have shown immense promise in the treatment of cancer and viral infections. The systematic evolution of transition‐metal‐catalyzed CC bond‐forming reactions has widened the scope of olefin metathesis. The development of new catalysts, the selectivity, efficiency, functional‐group compatibility, along with a better know‐how of the catalyst–substrate interactions have encouraged researchers to use this powerful tool for the design of desired target compounds. The aim of this Focus Review is to highlight recently developed synthetic strategies for the synthesis of carbocyclic nucleosides involving ring‐closing metathesis (RCM) as a key step.

The chemistry of the carbon-transition metal double and triple bond: Annual survey covering the year 2014

“…Specific compounds or compound classes represented include: (1) tetrahydropyrans [53]; (2) cyclopentenones [54]; (3) 3,4,5-trisubstituted isoxazolines [55]; (4) carbocyclic nucleosides [56]; (5) lycopodium alkaloids [57,58]; (6) cyclic hydrazines and azo compounds [59]; (7) tropone and tropolone natural products [60]; (8) seven-membered ring natural products [61]; [62]; (9) tetrahydroisoquinoline-3-carboxylic acid derivatives [63]; (10) chalcones and their heterocyclic derivatives [64]; (11) marine-derived cyclic ethers [65]; (12) pericosine and related marinederived carbasugar natural products [66]; (13) carbohydrate derived macrocyclic compounds [67]; (14) neurotrophic natural products [68]; (15) isodon diterpenes [69]; (16) non-isoprenoid polyene natural products [70]; (17) heterophosphacyclanes [71]; (18) chlorosulfolipids [72]; (19) seven-membered ring sulfur heterocycles; (20) organic cage compounds [73]; (21) presilphiperfolanols [74]; (22) pleuromutilin [75]; (23) hyperforin [76]; (24)…”

Phosphine-Catalyzed Chemo- and Diastereoselective [2 + 2 + 2] and [3 + 2] Annulations of γ-Methyl Allenoates with Doubly Activated Olefins: Syntheses of Highly Substituted Cyclohexanes and Cyclopentenes

“…Efficient construction of highly functionalized five- and six-membered carbocycles with a defined configuration is of significant importance in organic synthesis because of their widespread occurrence in natural products and pharmaceutically active compounds . Extensive efforts in this area have resulted in a plethora of synthetic methodologies including the Diels–Alder reaction, Nazarov cyclization, transition-metal-catalyzed ring-closing metathesis, and cycloisomerizations established as powerful ring-forming tools. Despite the effectiveness of these existing methods, there remains significant room for the development of additional complementary processes, especially aiming at challenging synthesis of poly-substituted carbocycles with multiple stereogenic centers in a highly diastereoselective manner.…”

2′‐Fluoro‐6′‐methylene carbocyclic adenosine and its phosphoramidate prodrug: A novel anti‐HBV agent, active against drug‐resistant HBV mutants

“…After the invention of carbovir and abacavir (prodrug of carbovir) for the treatment of HIV, carbocyclic nucleosides have gained significant attention for antiviral drug discovery. Carbocyclic nucleosides are unusual nucleosides in which the oxygen atom of the furanose ring has been replaced by a carbon atom . These nucleosides become more stable toward the nucleoside phosphorylase, as well as nucleoside hydrolase.…”

“…Carbocyclic nucleosides are unusual nucleosides in which the oxygen atom of the furanose ring has been replaced by a carbon atom. 21,22 These nucleosides become more stable toward the nucleoside phosphorylase, as well as nucleoside hydrolase. As a consequence, the glycosidic bond of carbocyclic nucleosides becomes more stable toward the metabolic degradation.…”