New drug approvals for 2020: Synthesis and clinical applications.

53 New drugs including 38 chemical entities and 15 biologics were approved by the U.S. Food and Drug Administration during 2020. Among the marketed drugs, 34 new small molecule drugs and 4 new diagnostic agents with privileged structures and novel clinical applications represent as promising leads for the development of new drugs with the similar indications and improved therapeutic efficacy. This review is mainly focused on the clinical applications and synthetic methods of 34 small-molecule drugs newly approved by the FDA in 2020.

Copper(ii)-catalyzed and acid-promoted highly regioselective oxidation of tautomerizable C(sp3)-H bonds adjacent to 3,4-dihydroisoquinolines using air (O2) as a clean oxidant.

A mild, efficient and eco-friendly method for the oxidation of 1-Bn-DHIQs to 1-Bz-DHIQs without concomitant excessive oxidation of 1-Bz-DHIQs to 1-Bz-IQs is very important for the syntheses of 1-Bz-DHIQ alkaloids and analogues. In this article, we developed a novel Cu(ii)-catalyzed and acid-promoted highly regioselective oxidation of tautomerizable C(sp3)-H bonds adjacent to the C-1 positions of various 1-Bn-DHIQs. It was observed that when 0.2 equiv. of Cu(OAc)2·2H2O was used as the catalyst, 3.0 equiv. of AcOH was used as the additive and air (O2) was used as a clean oxidant, various 1-Bn-DHIQs could be efficiently oxidized to corresponding 1-Bz-DHIQs at 25 °C in DMSO. Especially, almost no concomitant excessive oxidation of 1-Bz-DHIQs to 1-Bz-IQs was observed during the above reaction. In addition, this method was successfully applied in the first total synthesis of the alkaloid canelillinoxine.

Novel Stereoselective Syntheses of (+)-Streptol and (-)-1-epi-Streptol Starting from Naturally Abundant (-)-Shikimic Acid.

Novel highly stereoselective syntheses of (+)-streptol and (-)-1-epi-streptol starting from naturally abundant (-)-shikimic acid were described in this article. (-)-Shikimic acid was first converted to the common key intermediate by 11 steps in 40% yield. It was then converted to (+)-streptol by three steps in 72% yield, and it was also converted to (-)-1-epi-streptol by one step in 90% yield. In summary, (+)-streptol and (-)-1-epi-streptol were synthesized from (-)-shikimic acid by 14 and 12 steps in 29 and 36% overall yields, respectively.

Efficient and Highly Stereoselective Syntheses of (+)-proto-Quercitol and (-)-gala-Quercitol Starting from the Naturally Abundant (-)-Shikimic Acid.

Efficient and highly stereoselective syntheses of (+)-proto-quercitol and (-)-gala-quercitol starting from the naturally abundant (-)-shikimic acid were described in this article. (-)-Shikimic acid was first converted to the key intermediate by eight steps in 53% yield. It was then converted to (+)-proto-quercitol by three steps in 78% yield and was also converted to (-)-gala-quercitol by five steps in 63% yield. In summary, (+)-proto-quercitol and (-)-gala-quercitol were synthesized from (-)-shikimic acid by 11 and 13 steps in 41 and 33% overall yields, respectively.

Laparoscopic cholecystectomy for acute cholecystitis: early or delayed?: Evidence from a systematic review of discordant meta-analyses.

The laparoscopic cholecystectomy (LC) is an important approach of treating acute cholecystitis and the timing of performing this given treatment is associated with clinical outcomes. Although several meta-analyses have been done to investigate the optimal timing of implementing this treatment, the conflicting findings from these meta-analyses still confuse decision-making. And thus, we performed this systematic review to assess discordant meta-analyses and generate conclusive findings to facilitate informed decision-making in clinical context eventually. We electronically searched the PubMed, Cochrane Library, and EMBASE to include meta-analysis comparing early (within 7 days of the onset of symptoms) with delayed LC (at least 1 week after initial conservative treatment) for acute cholecystitis through August 2015. Two independent investigators completed all tasks including scanning and appraising eligibility, abstracting essential information using prespecified extraction form, assessing methodological quality using Oxford Levels of Evidence and Assessment of Multiple Systematic Reviews (AMSTAR) tool, and assessing the reporting quality using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), as well as implementing Jadad algorithm in each step for the whole process. A heterogeneity degree of ≤50% is accepted. Seven eligible meta-analyses were included eventually. Only one was Level I of evidence and remaining studies were Level II of evidence. The AMSTAR scores varied from 8 to 11 with a median of 9. The PRISMA scores varied from 19 to 26. The most heterogeneity level fell into the desired criteria. After implementing Jadad algorithm, 2 meta-analyses with more eligible RCTs were selected based on search strategies and implication of selection. The best available evidence indicated a nonsignificant difference in mortality, bile duct injury, bile leakage, overall complications, and conversion to open surgery, but a significant reduction in wound infection, hospitalization, and operation duration and improvement of the quality of life when compared early LC with delayed LC. However, number of work days lost, hospital costs, and patient satisfaction are warranted to be assessed further. With the best available evidence, we recommend early LC to be as the standard treatment option in treating acute cholecystitis.