Construction of a chiral quaternary carbon center by a radical cyclization/ring-enlargement reaction: synthesis of 4α-azidoethyl carbocyclic ribose, a key unit for the synthesis of cyclic ADP-ribose derivatives of biological importance

Design, Synthesis, and Identification of 4″α-Azidoethyl-cyclic ADP-Carbocyclic-ribose as a Highly Potent Analogue of Cyclic ADP-Ribose, a Ca2+-Mobilizing Second Messenger

“…We planned to construct the N1-carbocyclic-ribosyl adenosine derivative 6 by an adenine ring-closure reaction between the 4α-branched carbocyclic-ribosylamine 4 , which has a quaternary stereogenic carbon center at the 4-position, and a known imidazole nucleoside derivative 5 prepared from inosine . Stereocontrolled construction of quaternary stereogenic carbon centers is one of the most challenging issues in organic chemistry, but we recently succeeded in synthesizing the 4α-branched carbocyclic-ribosylamine 4 , in which the key quaternary carbon center was effectively constructed using a radical cyclization/ring-enlargement reaction with a silicon tether . Thus, the 4α-branched carbocyclic-ribosylamine 4 in hand, its reaction with the imidazole nucleoside derivative 5 in the presence of K 2 CO 3 in DMF/THF effectively induced adenine ring closure to produce the desired N1-carbocyclic-ribosyl adenosine derivative 6 .…”

Synthesis of 4′-Substituted Carbocyclic Uracil Derivatives and Their Monophosphate Prodrugs as Potential Antiviral Agents

“…The targeted 4′-alkyno, 4′-cyano and 4′-chloromethyl carbocyclic ribonucleoside analogs ( 9 – 11 ) along with their corresponding prodrugs ( 12 – 14 ) were prepared from the same carbocyclic uridine precursor ( 15 ), which was synthetized from the (-)-Vince lactam in 8 steps (47% yield) following reported procedures [ 25 , 26 , 27 ]. Compound ( 15 ) was first per -silylated with tert -butyldimethylsilyl chloride (TBDMSCl) in presence of imidazole before selective 5′-deprotection, in presence of trifluoroacetic acid (TFA) and water, to afford compound ( 16 ) in 62% yield over 2 steps.…”

Tethered 1,2-Si-Group Migrations in Radical-Mediated Ring Enlargements of Cyclic Alkoxysilanes: An EPR Spectroscopic and Computational Investigation

“…When the alcohol segment contains a substituent β-to the oxygen atom, that is suitable as a leaving group for radical generation ( 1 , Scheme ), then homolytic ring closure affords cyclic alkoxysilanes . The latter readily yield diols when oxidatively ring-opened with fluoride under Tamao conditions. , This sequence has been exploited in successful preparations of branched nucleosides and C-glycosides. , …”