102717-29-3Relevant articles and documents
Synthesis of 1′,2′-methano-2′,3′-dideoxynucleosides as potential antivirals
Rico, Lorena,Hanessian, Stephen
, p. 597 - 600 (2019)
The synthesis of constrained nucleosides has become an important tool to understand the SAR in the interaction between biological and synthetic nucleotides in the context of antisense oligonucleotide therapy. The incorporation of a cyclopropane into a furanose ring of a nucleoside induces some degree of constrain without affecting significantly the steric environment of a nucleoside. Here, we report a new, short and stereocontrolled synthesis of two constrained nucleosides analogues, 1′,2′- methano-2′,3′-dideoxyuridine 9, and the corresponding cytidine analog 12. X-ray crystallography revealed that the furanose ring in the constrained uridine and cytidine analogues was flattened with virtual loss of pseudorotation. The phosphoramidate esters of the novel constrained uridine and cytidine nucleosides, intended as prodrugs, were tested in cell-based assays for viral replication across the herpes virus family and HIV inhibition courtesy of Merck laboratories, Rahway. They were also tested in antiproliferative assays against colorectal and melanoma cell lines. Unfortunately, none of the compounds showed activity in these assays.
Synthesis and biological properties of the four optical isomers of 5-o- carboranyl-2',3'-didehydro-2',3'-dideoxyuridine
Graciet, Jean-Christophe G.,Shi, Junxing,Schinazi, Raymond F.
, p. 711 - 727 (1998)
The four isomers of the 5-o-carboranyl-2',3'-didehydro-2',3'- dideoxyuridine (d4CU) were synthesized and their antiviral activity and cytotoxicity in normal and cancer human cells determined. Coupling of silylated 5-o-carboranyluracil with the protected D/L 2,3-dideoxy-2- phenylselenenylribosylacetates provided after oxidative elimination and deprotection, the desired compounds. The presence of the electron deficient 5-o-carboranyl moiety on uracil influenced the yield of the various isomers. In general, the compounds demonstrated weak anti-human immunodeficiency virus activity in primary human lymphocytes. No marked difference in the biological profile was noted for the various optical isomers, suggesting that the high lipophilicity of these nucleosides imparted by the carboranyl moiety overrides stereochemical considerations in the 2',3'-didehydro-2',3'- dideoxyaglycon moiety.
Synthesis of Alkyl Citrates (-)-CJ-13,981, (-)-CJ-13,982, and (-)-L-731,120 via a Cyclobutene Diester
Atkin, Liselle,Chen, Zongjia,Robertson, Angus,Sturgess, Dayna,White, Jonathan M.,Rizzacasa, Mark A.
, p. 4255 - 4258 (2018)
An efficient and step-economic new approach to alkyl citrate natural products from a cyclobutene diester is presented. The key sequence involves a formal [2 + 2]-cycloaddition of a silylketene acetal with dimethylacetylene dicarboxylate to provide the cyclobutene diester 14 with 4.5:1 stereoselectivity. Exposure of diester 14 in acidic methanol effected a hydrolysis, intramolecular oxy-Michael reaction, and cyclobutanone methanolysis cascade to give the triester 15. Iodination and elimination then afforded a key alkyl citrate alkene intermediate, which was converted into the natural products (-)-CJ-13,982 (1), (-)-CJ-13,981 (2), and (-)-L-731,120 (3) via a cross-metathesis and subsequent reduction.
