Exo-Selective Diels-Alder Reactions.

The Diels-Alder reaction stands as one of the most pivotal transformations in organic chemistry. Its efficiency, marked by the formation of two carbon-carbon bonds and up to four new stereocenters in a single step, underscores its versatility and indispensability in synthesizing natural products and pharmaceuticals. The most significant stereoselectivity feature is the "endo rule". While this rule underpins the predictability of the stereochemical outcomes, it also underscores the challenges in achieving the opposite diastereoselectivity, making the exo-Diels-Alder reactions often considered outliers. This review delves into recent examples of exo-Diels-Alder reactions, shedding light on the factors inverting the intrinsic tendency. We explore the roles of steric, electrostatic, and orbital interactions, as well as thermodynamic equilibriums in influencing exo/endo selectivity. Furthermore, we illustrate strategies to manipulate these factors, employing approaches such as bulky substituents, s-cis conformations, transient structural constraints, and innovative control physics. Through these analyses, our aim is to provide a comprehensive understanding of how to predict and design exo-Diels-Alder reactions, paving the way for new diastereoselective catalyst systems and expanding the chemical scope of Diels-Alder reactions.

Total Synthesis of (+)-Haperforin G.

(+)-Haperforin G was synthesized in 20 steps from commercially available starting materials. A Co-catalyzed intramolecular Pauson-Khand reaction was used for stereoselective construction of cyclopentanone bearing an all-carbon quaternary stereogenic center at the bridge-head position. Light-initiated photocatalysis was used for convergent and asymmetric cross-coupling of the unstabilized C(sp3) radical with an enone. The developed chemistry paves the way to the synthesis of structurally diverse analogs of haperforin G (6).

Highly Stereoselective Diels-Alder Reactions Catalyzed by Diboronate Complexes.

A highly enantioselective catalytic system for exo-Diels-Alder reactions was developed based on the newly discovered bispyrrolidine diboronates (BPDB). Activated by various Lewis or Brønsted acids, BPDB can catalyze highly stereoselective asymmetric exo-Diels-Alder reactions of monocarbonyl-based dienophiles. When 1,2-dicarbonyl-based dienophiles are used, the catalyst can sterically distinguish between the two binding sites, which leads to highly regioselective asymmetric Diels-Alder reactions. BPDB can be prepared as crystalline solids on a large scale and are stable under ambient condition. Single-crystal X-ray analysis of the structure for acid-activated BPDB indicated that its activation involves cleavage of a labile B←N bond.

Asymmetric Total Synthesis of (-)-Spirochensilide A, Part 2: The Final Phase and Completion.

The final phase of the total synthesis of (-)-spirochensilide A is described. A tungsten-mediated cyclopropene-based Pauson-Khand reaction was developed to form the spiral CD ring system with desired stereochemistry at the C13 quaternary center. Other important steps enabling completion of this synthesis included an intermolecular aldol condensation to link the ABCD core with the EF fragment and a Cu-mediated 1,4-addition to stereoselectively install the C21 stereogenic center. The chemistry developed for this total synthesis of (-)-spirochensilide A (1) will aid the synthesis of polycyclic natural products bearing this unique spiral ring system.

Asymmetric Total Synthesis of (-)-Spirochensilide A, Part 1: Diastereoselective Synthesis of the ABCD Ring and Stereoselective Total Synthesis of 13(R)-Demethyl Spirochensilide A.

A concise and diastereoselective construction of the ABCD ring system of spirochensilide A is described. The key steps of this synthesis are a semipinacol rearrangement reaction to stereoselectively construct the AB ring system bearing two vicinal quaternary chiral centers and a Co-mediated Pauson-Khand reaction to form the spiro-based bicyclic CD ring system. This chemistry leads to the stereoselective synthesis of 13(R)-demethyl spirochensilide A, paving the way for the first asymmetric total synthesis of (-)-spirochensilide A.

Clinical features and prognostic factors of cervical villoglandular adenocarcinoma.

BACKGROUND: Villoglandular adenocarcinoma is a rare sub-type of cervical adenocarcinoma. OBJECTIVE: To analyze the clinicopathological features and evaluate the prognosis of patients with villoglandular adenocarcinoma of the cervix. METHODS: Patient characteristics, procedure, pathology, and surgical outcomes were retrospectively reviewed in patients with villoglandular adenocarcinoma between November 2006 and June 2019 from multiple centers in China. In order to explore the difference between villoglandular adenocarcinoma and routine adenocarcinoma, patients (FIGO 2009 stage IA1-IB2) who had complete data during the same time period were included. RESULTS: A total of 60 patients with villoglandular adenocarcinoma and 104 with standard adenocarcinoma were included. The median age of the patients with villoglandular adenocarcinoma was 42 years (range 27-68). The most common 2009 FIGO stage was IB1 in 39 (65%) patients with villoglandular adenocarcinoma. A total of 23 patients underwent laparoscopic surgery (two total hysterectomies, 21 radical hysterectomies) and the other 37 patients underwent laparotomy (three total hysterectomies, 34 radical hysterectomies). A total of 56 patients underwent lymphadenectomy and three (5.4%) had positive lymph nodes. Fifteen (25%) patients had one or both ovaries preserved. Seven patients were lost to follow-up. The median follow-up time for the entire group was 50.2 months (range 5.1-154.6). No deaths or recurrences occurred. Excluding six patients with FIGO 2009 stage II, the 5-year disease-free survival of the 47 patients with villoglandular adenocarcinoma with FIGO 2009 stage I for whom there was follow-up, was significantly higher than that of the 104 patients with standard cervical adenocarcinoma (100% vs 92.2%, log-rank p=0.039). However, the 5-year overall survival of the two groups did not differ (100% vs 95.7%, log-rank p=0.11). CONCLUSION: Villoglandular adenocarcinoma has a favorable prognosis. Further studies are needed to provide more details of treatment strategies and prognosis.

Asymmetric Total Synthesis of (-)-Spirochensilide A.

An asymmetric total synthesis of (-)-spirochensilide A has been achieved for the first time. The synthesis features a semipinacol rearrangement reaction to stereoselectively construct the two-vicinal quaternary chiral centers at C8 and C10, a tungsten-mediated cyclopropene-based Pauson-Khand reaction to install the C13 quaternary chiral center, and a furan-based oxidative cyclization to stereoselectively form the spiroketal motif.

Asymmetric Total Synthesis of Pre-schisanartanin C.

Pre-schisanartanin C belongs to the family of Schisandra nortriterpenoids with potent antihepatitis, antitumor, and anti-HIV activities. This paper presents the enantioselective total synthesis of pre-schisanartanin C (1). An important step in the total synthesis of 1 is gold-catalyzed intramolecular cyclopropanation of a 1,8-enyne substrate bearing a secondary ester group at the propargylic position to prepare a bicyclo[6.1.0]nonane core. Additional highlights include (i) an asymmetric Diels-Alder reaction to install the initial C5 stereogenic center of 1 and (ii) a sequential Pd-catalyzed Stille coupling, regio- and stereoselective Sharpless asymmetric dihydroxylation, and a subsequent intramolecular lactonization to construct the side chain of 1. The developed chemistry paves the way for the total syntheses of other family members bearing highly rigid bicyclo[6.1.0]nonane cores.

Total Synthesis of (+)-Haperforin G.

A concise chemical synthesis of (+)-haperforin G in 20 steps from commercially available starting materials is achieved with the integration of the Co-catalyzed intramolecular Pauson-Khand reaction for the stereoselective construction of cyclopentanone bearing an all-carbon quaternary stereogenic center at the bridge-head position and the light-initiated photocatalysis for convergent and asymmetric cross-coupling of the unstabilized C(sp3)-radical with an enone. The developed chemistry paves the way to synthesizing structurally diverse analogs of haperforin G (6).

Asymmetric Total Synthesis of Lancifodilactone G Acetate. 1. Diastereoselective Synthesis of CDEFGH Ring System.

The stereoselective construction of the CDEFGH ring system of lancifodilactone G is described. The key steps in this synthesis are (i) ring-closing metathesis for formation of the oxa-bridged eight-membered ring; (ii) an intramolecular Pauson-Khand reaction for construction of the sterically congested F ring; and (iii) sequential cross-metathesis, hydrogenation, and lactonization reactions for installation of the anomerically stabilized bis-spiro ketal fragment of lancifodilactone G.

Asymmetric Total Synthesis of Lancifodilactone G Acetate. 2. Final Phase and Completion of the Total Synthesis.

The asymmetric total synthesis of lancifodilactone G acetate was accomplished in 28 steps. The key steps in this synthesis include (i) an asymmetric Diels-Alder reaction for formation of the scaffold of the BC ring; (ii) an intramolecular ring-closing metathesis reaction for the formation of the trisubstituted cyclooctene using a Hoveyda-Grubbs II catalyst; (iii) an intramolecular Pauson-Khand reaction for construction of the sterically congested F ring; (iv) sequential cross-metathesis, hydrogenation, and lactonization reactions for installation of the anomerically stabilized bis-spiro ketal fragment of lancifodilactone G; and (v) a Dieckmann-type condensation reaction for installation of the A ring. The strategy and chemistry developed for the total synthesis will be useful in the synthesis of other natural products and complex molecules.

Asymmetric Total Synthesis of Lancifodilactone G Acetate.

Asymmetric total synthesis of structurally intriguing and highly oxygenated lancifodilactone G acetate (7) has been achieved for the first time in 28 steps from a cheap commodity chemical, 2-(triisopropylsiloxy)-1,3-butadiene.

Intramolecular cyclization of diarylmethanols and α,ß-unsaturated amides promoted by KOt-Bu/DMF: a metal-free approach towards 3,4-disubstituted quinolinones.

A facile synthesis of quinolinones through intramolecular addition of diarylmethanols to α,ß-unsaturated amides promoted by KOt-Bu/DMF is reported. A series of 3,4-disubstituted quinolinones were obtained in moderate to good yields. A reaction pathway via the ketyl radical is proposed.

Intramolecular addition of diarylmethanols to imines promoted by KOt-Bu/DMF: a new synthetic approach to indole derivatives.

KOt-Bu/DMF promoted intramolecular addition of diarylmethanols to imines was developed. A series of 2,3-disubstituted indoles was obtained in good yields. A reaction mechanism of radical cyclization and subsequent dehydration is proposed.

Asymmetric Total Synthesis of Propindilactone G.

A concise total synthesis of (+)-propindilactone G, a nortriterpenoid isolated from the stems of Schisandra propinqua var. propinqua, has been achieved for the first time. The key steps of the synthesis include an asymmetric Diels-Alder reaction, a Pauson-Khand reaction, a Pd-catalyzed reductive hydrogenolysis reaction, and an oxidative heterocoupling reaction. These reactions enabled the synthesis of (+)-propindilactone G in only 20 steps. As a consequence of our synthetic studies, the structure of (+)-propindilactone G has been revised.

Direct inter- and intramolecular addition of amides to arylalkenes promoted by KOt-Bu/DMF.

Direct addition of tetrahydroisoquinoline derived amides to arylalkenes has been achieved in the presence of KOt-Bu/DMF. Both intermolecular and intramolecular reactions could occur in good yields. α-Amido alkyl radicals are proposed to be generated under the reaction conditions. The reaction is efficient for the synthesis of seven-membered nitrogen heterocycles. A homoprotoberberine was prepared conveniently via this method.

The discovery of the rare genus Epimicta Foerster (Hymenoptera: Braconidae) in China, with a description of a new species.

Epimicta sulciscutum sp. nov. from Heilongjiang (North China) is described and illustrated. A key to species of the genus is provided.

Regioselective Hydroxylation of Flavonoids by Transition-Metal-Catalyzed C-H Bond Oxidation.

Regioselective synthesis of 5,6,7-trihydroxyl and 5,7,8-trihydroxyl flavones has been achieved via a transition-metal-catalyzed C-H oxidation as the key step using naturally enriched 5,7-dihydroxyl flavone. The developed chemistry was applied to the synthesis of the naturally occurring and biologically active flavonoids wogonin (2), oroxylin A (3), and their glycosylated derivatives (4 and 5) as potential carnitine palmitoyltransferase 1 activators.

Synthesis towards Phainanoid F: Photo-induced 6π-Electrocyclization for Constructing Contiguous All-Carbon Quaternary Centers.

In this paper, we report an efficient strategy for synthesizing the DEFGH rings of phainanoid F. The key to the construction of the 13,30-cyclodammarane skeleton of the molecule was a photo-induced 6π-electrocyclization and a homoallylic elimination. Notably, this is a rare example of using electrocyclization reaction to simultaneously construct two vicinal quaternary carbons in total synthesis. The strategy outlined here forms the basis of our total synthesis of Phainanoid F, and it could also serve as a generally applicable approach for synthesizing other natural products containing similar 13,30-cyclodammarane skeletons.

Recent Insights into Noncoding RNAs in Primary Ovarian Insufficiency: Focus on Mechanisms and Treatments.

CONTEXT: Primary ovarian insufficiency (POI) is a heterogeneous disease with an unknown underlying trigger or root cause. Recently many studies evaluated noncoding RNAs (ncRNAs), especially microRNAs (miRNAs), long noncoding RNA (lncRNAs), circular RNAs (circRNAs), and small interfering RNAs (siRNAs) for their associations with POI. EVIDENCE ACQUISITION: In this review, we outline the biogenesis of various ncRNAs relevant to POI and summarize the evidence for their roles in the regulation of disease occurrence and progression. Articles from 2003 to 2022 were selected for relevance, validity, and quality from results obtained in PubMed and Google Scholar using the following search terms: noncoding RNAs; primary ovarian insufficiency; premature ovarian failure; noncoding RNAs and primary ovarian insufficiency/premature ovarian failure; miRNAs and primary ovarian insufficiency/premature ovarian failure; lncRNAs and primary ovarian insufficiency/premature ovarian failure; siRNAs and primary ovarian insufficiency/premature ovarian failure; circRNAs and primary ovarian insufficiency/premature ovarian failure; pathophysiology; and potential treatment. All articles were independently screened for eligibility by the authors. EVIDENCE SYNTHESIS: This review summarizes the biological functions and synthesis of miRNAs, lncRNAs, siRNAs, and circRNAs in POI and discusses the findings of clinical and in vitro and in vivo studies. Although there is variability in the findings of individual studies, overall the available literature justifies the conclusion that dysregulated ncRNAs play significant roles in POI. CONCLUSION: The potential of ncRNAs in the treatment of POI requires further investigation, as ncRNAs derived from mesenchymal stem cell-secreted exosomes play pivotal roles and have considerable therapeutic potential in a multitude of diseases.