RESUMO
Given the importance and beneficial characteristics of decorated azetidines in medicinal chemistry, efficient strategies for their synthesis are highly sought after. Herein, we report a facile synthesis of the elusive all-carbon quaternary-center-bearing azetidines. By adopting a well-orchestrated polar-radical relay strategy, ring strain release of bench-stable benzoylated 1-azabicyclo[1.1.0]butane (ABB) can be harnessed for nickel-catalyzed Suzuki Csp2-Csp3 cross-coupling with commercially available boronic acids in broad scope (>50 examples), excellent functional group tolerance, and gram-scale utility. Preliminary mechanistic studies provided insights into the underlying mechanism, wherein the ring opening of ABB with a catalytic quantity of bromide accounts for the conversion of ABB into a redox-active azetidine, which subsequently engages in the cross-coupling reaction through a radical pathway. The synergistic bromide and nickel catalysis could intriguingly be derived from a single nickel source (NiBr2). Application of the method to modify natural products, biologically relevant molecules, and pharmaceuticals has been successfully achieved as well as the synthesis of melanocortin-1 receptor (MC-1R) agonist and vesicular acetylcholine transporter (VAChT) inhibitor analogues through bioisosteric replacements of piperidine with azetidine moieties, highlighting the potential of the method in drug optimization studies. Aside from the synthesis of azetidines, we demonstrate the ancillary utility of our nickel catalytic system toward the restricted Suzuki cross-coupling of tertiary alkyl bromides with aryl boronic acids to construct all-carbon quaternary centers.
RESUMO
INTRODUCTION: The traditional procedure for the management of bilateral ureteral stones is staged ureteroscopic lithotripsy (URS). However, in recent years particularly, some urologists advocate same-session bilateral URS on the ground of success rates and minimal morbidity. This systematic review is to evaluate the efficacy and safety of same-session bilateral ureteroscopy for the treatment of ureteral calculi. MATERIALS AND METHODS: We conducted a bibliographic search using MEDLINE (1980 to August 2015) and EMBASE (1980 to August 2015). Review articles and abstract data were excluded and only studies in English reporting on outcomes of bilateral URS were included in this meta-analysis. Two reviewers independently assessed the quality of each included studies and extracted data. STATA 12.0 was used for meta-analysis. RESULTS: In 11 studies, 431 patients were reportedly treated with bilateral URS. Most of the stone sizes were not larger than 20 mm. The mean stone-free rate is 96% for the distal ureter, 85% for the middle ureter, and 72% for the proximal ureter. The mean operative time ranged from 45 to 100 minutes with an average hospital stay from 2 to 4 days. The overall complications rates were 17%, with the incidence of postoperative fever 4%, postoperative pain 20%, and gross hematuria 4%. Other complications, including urosepsis, urinary tract infection, small mucosal laceration, stone migration, and ureteral perforation, accounted for 6% of overall complications. CONCLUSIONS: This meta-analysis found that bilateral same-session ureteroscopy could achieve a high overall stone-free rate. There might be a relatively higher complication incidence, but most of the complications are minor. For selected cases, bilateral URS could be safe and effective.
