Browsing by Subject "Pyrazoles"
Now showing 1 - 2 of 2
- Results Per Page
- Sort Options
Item [3+2]-Cycloadditions of Azomethine Imines and Ynolates and Progress Towards a Radical Three-Component Cross-Coupling Reaction(2018-07-16) Winterton, Sarah Elizabeth; Chen, Chuo; Tambar, Uttam; De Brabander, Jef K.; Ready, Joseph M.This manuscript consists of three chapters. The first chapter describes a novel [3+2]-cycloaddition of azomethine imines and ynolates to construct bicyclic pyrazolidinones in high yields and diastereoselectivities. This methodology is the first example in which the azomethine imine acts as a chiral auxiliary to control the cycloaddition. Optically active azomethine imines yield bicyclic pyrazolidinones in high yields, and conditions for removal of the azomethine imine chiral auxiliary have been defined to yield optically active monocyclic pyrazolidinones in high yields and enantioselectivities. The second chapter consists of progress towards a novel [2+2]-annulation/fragmentation to construct cyclohexanones. Among all the methods to synthesize highly substituted cyclohexanols/cyclohexanones, there is no general, one-step enantioselective, intermolecular method to synthesize a highly substituted cyclohexanol/cyclohexanone with a quaternary center at C4. Therefore, we developed a synthesis of cyclohexanones via a formal [2+2]-annulation/fragmentation between a cyclobutanone containing an electron-withdrawing group and an electrophile. The second chapter describes attempts to render the reaction asymmetric, which proved to be difficult. Future ideas to improve yields and to render the reaction asymmetric are also described. The last chapter involves progress towards a novel three-component, enantioselective radical cross-coupling reaction to synthesize complex products in a single step. Current literature contains only scattered examples of three-component radical cross-coupling reactions, all of which have a severely limited substrate scope (e.g., only alkynes, one nucleophile, contains fluorine). Therefore, we envisioned a three-component radical cross-coupling reaction with a broad substrate scope encompassing multiple radical initiators and olefin acceptors. This method could provide access to products that are currently challenging to synthesize. Progress towards this three-component enantioselective reaction is presented in chapter three, as well as future ideas to improve enantioselectivity and yields.Item Effect of Perioperative Celecoxib on Patient Outcomes After Major Plastic Surgery Procedures(2008-12-23) Sun, Tiffany B.; White, Paul F.BACKGROUND: Controversy continues to surround the use of COX-2 inhibitors in the perioperative period. This randomized, double-blind, placebo-controlled study was designed to examine the hypothesis that administration of celecoxib preoperatively or postoperatively and for a total of 4 days after major plastic surgery would improve pain control and clinically-important patient outcomes. Another objective of the study was to determine if perioperative administration of celecoxib offered any advantages over postoperative administration alone. METHODS: One hundred and twenty healthy consenting patients undergoing major plastic surgery (e.g., breast augmentation, abdominoplasty procedures) utilizing a standardized general anesthetic technique were randomized to one of three treatment groups: (1) Control group (n=40) received two placebos orally before and after surgery, as well as one placebo BID for three days after surgery (2) Postoperative group (n=40) received two placebos before surgery and two celecoxib 200 mg po after surgery, followed by one celecoxib 200 mg po BID on POD #1, #2 and #3, and (3) Perioperative group (n=40) received two celecoxib 200 mg po 30-90 minutes before surgery and two placebos after surgery, followed by one celecoxib 200 mg po BID on POD #1, #2 and #3. Pain scores, the need for "rescue" analgesics, and side effects were recorded at specific time intervals in the postoperative period. Follow-up evaluations were performed at 24 h, 48 h, 72 h and 7 d after surgery to assess post-discharge pain, analgesic requirements, return of bowel function, resumption of normal daily activities, quality of recovery, and patients' satisfaction with their pain management. RESULTS: Compared to the Control group, the two celecoxib groups had similarly significant reductions in postoperative pain and need for opioid analgesics during the first three postoperative days (p<0.01). Patients recovered bowel function 1 d earlier and resumed normal activities 2 d earlier in the celecoxib groups. In addition, patient satisfaction with pain management and quality of recovery were significantly improved in the celecoxib (vs. control) groups (p<0.05). CONCLUSION: Celecoxib (400 mg po) administered on the day of surgery and for three days postoperatively is effective in improving postoperative pain management, as well as the speed and quality of recovery after major plastic surgery. However, perioperative administration offers no advantages over simply giving the drug after surgery.