81691-32-9Relevant academic research and scientific papers
A practical synthesis of xylo- and arabinofuranoside precursors by diastereoselective reduction using Corey-Bakshi-Shibata catalyst
Utley, Lynn M.,Maldonado, Jessica,Awad, Ahmed M.
, p. 20 - 34 (2018/02/06)
The Corey-Bakshi-Shibata (CBS) catalyst provides an efficient mechanism to reduce ketones and achieve desired enantiopure alcohols. Herein, the diastereoselective reduction of C-2′ and C-3′-keto ribofuranoside derivatives to the corresponding arabino- and xylofuranosides in greater than 95% diastereomeric excess is reported. The stereo-directed substitution with an azido group as well as the synthesis of prodrugs cytarabine and vidarabine are also described. The reported strategy offers superior diastereoselectivity, shorter reaction times, and obviates cooling required with comparable protocols involving achiral reductants.
Synthesis and antibacterial activity of 5′-tetrachlorophthalimido and 5′-azido 5′-deoxyribonucleosides
Van Ostrand, Robert,Jacobsen, Casey,Delahunty, Alicia,Stringer, Carley,Noorbehesht, Ryan,Ahmed, Haidi,Awad, Ahmed M.
, p. 181 - 197 (2017/02/15)
Reported is an efficient synthesis of adenyl and uridyl 5′-tetrachlorophthalimido-5′-deoxyribonucleosides, and guanylyl 5′-azido-5′-deoxyribonucleosides, which are useful in solid-phase synthesis of phosphoramidate and ribonucleic guanidine oligonucleotides. Replacement of 5′-hydroxyl with tetrachlorophthalimido group was performed via Mitsunobu reaction for adenosine and uridine. An alternative method was applied for guanosine which replaced the 5′-hydroxyl with an azido group. The resulting compounds were converted to 5′-amino-5′-deoxyribonucleosides for oligonucleotide synthesis. Synthetic intermediates were tested as antimicrobials against six bacterial strains. All analogs containing the 2′,3′-O-isopropylidine protecting group demonstrated antibacterial activity against Neisseria meningitidis, and among those analogs with 5′-tetrachlorophthalimido and 5′-azido demonstrated increased antibacterial effect.
Synthesis of Dimeric ADP-Ribose and Its Structure with Human Poly(ADP-ribose) Glycohydrolase
Lambrecht, Michael J.,Brichacek, Matthew,Barkauskaite, Eva,Ariza, Antonio,Ahel, Ivan,Hergenrother, Paul J.
, p. 3558 - 3564 (2015/03/30)
Poly(ADP-ribosyl)ation is a common post-translational modification that mediates a wide variety of cellular processes including DNA damage repair, chromatin regulation, transcription, and apoptosis. The difficulty associated with accessing poly(ADP-ribose) (PAR) in a homogeneous form has been an impediment to understanding the interactions of PAR with poly(ADP-ribose) glycohydrolase (PARG) and other binding proteins. Here we describe the chemical synthesis of the ADP-ribose dimer, and we use this compound to obtain the first human PARG substrate-enzyme cocrystal structure. Chemical synthesis of PAR is an attractive alternative to traditional enzymatic synthesis and fractionation, allowing access to products such as dimeric ADP-ribose, which has been detected but never isolated from natural sources. Additionally, we describe the synthesis of an alkynylated dimer and demonstrate that this compound can be used to synthesize PAR probes including biotin and fluorophore-labeled compounds. The fluorescently labeled ADP-ribose dimer was then utilized in a general fluorescence polarization-based PAR-protein binding assay. Finally, we use intermediates of our synthesis to access various PAR fragments, and evaluation of these compounds as substrates for PARG reveals the minimal features for substrate recognition and enzymatic cleavage. Homogeneous PAR oligomers and unnatural variants produced from chemical synthesis will allow for further detailed structural and biochemical studies on the interaction of PAR with its many protein binding partners. (Chemical Equation Presented).
The PdCl2/R3SiH system for the silylation of nucleosides
Ferreri,Costantino,Romeo,Chatgilialoglu
, p. 1197 - 1200 (2007/10/03)
Convenient syntheses of TIPDS-Cl2 and TBDMS-Br from the corresponding hydrides were obtained by using catalytic PdCl2 and CCl4 or CH2Br2, respectively. These systems can be successfully applied in tandem procedures for improved silylation of nucleosides.
