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The organocatalytic synthesis of densely substituted mono- and bis-γ-lactams involving the Mukaiyama Mannich addition of 2,5-bis­(trimethyl­silyloxy)­furan to imines is described. Use of a ditoluene­sulfonylimide catalyst produces γ-lactams from monoaddition, whereas a more acidic catalyst (triflic acid) produces fused bis-lactams from double addition. Optimized organocatalytic conditions allow for the selective synthesis of either desired core as well as the one-pot, multicomponent assembly of the trisubstituted monolactams from aldehydes, amines, and bis-trimethylsilyloxyfuran. An examination of chiral acids found these organocatalysts to be highly active and diastereoselective in the monoaddition reaction, albeit with no enantioselectivity.

The treatment of 2-(2-vinylphenyl)acetaldehydes or 3-(2-vinylphenyl)propanals with BF3·Et2O results in an intramolecular Prins reaction affording intermediary benzyl carbenium ions, which are then trapped by a variety of electron-rich aromatics via Friedel–Crafts alkylation. This cascade Prins/Friedel–Crafts cyclization protocol paves an expedient path to medicinally useful 4-aryltetralin-2-ol and 5-aryltetrahydro-5H-benzo[7]annulen-7-ol derivatives.

In the presence of boron trifluoride, a variety of alkynyl sulfides and alkynyl sulfoxides undergo tandem cross-coupling/[3,3]-sulfonium rearrangement followed by 5-exo-dig heterocyclization. The strategy provides concise access to novel tetrasubstituted furans in good to high yields with 100% atom-economy efficiency. Further derivatization of the resultant furans was feasible by utilizing the incorporated alkylthio groups.

A new synthesis of dihydromotuporamine C (dhMotC), a synthetic analogue of cytotoxic marine alkaloid, has been achieved from inexpensive starting materials. The first stage was the preparation of cyclodecanone by sequential [2+2]‐cycloaddition of N‐(1‐cycloocten‐1‐yl)pyrrolidine with methyl propiolate and electrocyclic ring‐opening, followed by basic hydrolysis. Beckmann rearrangement of cyclodecanone oxime and several step manipulations afforded the pivotal intermediate of the N‐benzylated 11‐membered cyclic α‐vinylamine. The final synthesis of dihydromotuporamine C involved tandem nucleophilic addition with ethynyl p‐tolyl sulfone and 3‐azonia‐Cope rearrangement to form the 15‐membered aza‐macrocycle and reductive amination to install the appended spermidine‐like moiety.

BackgroundPolycystic ovary syndrome (PCOS), the most common heterogeneous reproductive disease afflicting women of childbearing age, has been recognized as a chronic inflammatory disease recently. Most PCOS patients have hyperandrogenism, indicating a poor prognosis and poor pregnancy outcomes. The molecular mechanism underlying PCOS development is still unknown. In the present study, we investigated the gene expression profiling characteristics of PCOS with hyperandrogenism (HA) or without hyperandrogenism (NHA) and identified immune-related factors that correlated with embryo implantation failure.MethodsPCOS and recurrent implantation failure (RIF) microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. ClueGO software was used to perform enrichment analysis of differentially expressed genes (DEGs) in PCOS with varying androgen levels. The Weighted Co-Expression Network Analysis (WGCNA) was used to identify co-expressed modules and shared gene signatures between HA PCOS and RIF. Moreover, the upregulated DEGs of HA PCOS and RIF were intersected with shared gene signatures screening by WGCNA to excavate further key prognostic biomarkers related to implantation failure of HA PCOS. The selected biomarker was verified by qRT-PCR.ResultsA total of 271 DEGs were found in HA PCOS granulosa cell samples, and 720 DEGs were found in NHA PCOS. According to CuleGO enrichment analysis, DEGs in HA PCOS are enriched in immune activation and inflammatory response. In contrast, DEGs in NHA PCOS are enriched in mesenchymal cell development and extracellular space. Using WGCNA analysis, we discovered 26 shared gene signatures between HA PCOS and RIF, which were involved in corticosteroid metabolism, bone maturation and immune regulation. DAPK2 was furtherly screened out and verified to be closely related with the development of HA PCOS, acting as an independent predictor biomarker of the embryo implantation failure. DAPK2 expression was negatively correlated to the embryo implantation rate (r=-0.474, P=0.003). The immune infiltration results suggested that upregulated DAPK2 expression was closely related with NK cell infiltration and macrophage M2, playing an essential role in the pathogenesis of implantation failure in HA PCOS.ConclusionOur research revealed the expression profiling of PCOS with different androgen levels and identified DAPK2 as a critical prognostic biomarker for implantation failure in PCOS.

A tandem Prins/Friedel-Crafts cascade strategy has been developed for the synthesis of hexahydro-2Hbenzo[g]chromene derivatives. Under action of equimolecular amount of BF 3 etherate, δ,ε-unsaturated alcohols and arylacetaldehydes are coupled to form oxocarbenium ion intermediates, which are captured by the alkene moiety through a favored six-membered transition state. The Prins-cyclization resultant tertiary carbenium ions undergo consecutive intra-molecular Friedel-Crafts cyclization to create the tricyclic products. This process enables a tandem formation of three new chemical bonds in one single operation with high yields and stereoselectivity in most cases. When cyclic substituents are involved, a variety of spiro derivatives could also be synthesized successfully, which further proved the robustness of this methodology.

Various fractures and holes in the natural rock mass affected the mechanical properties of the rock mass and the safety construction of engineering. In this study, we investigated the mechanical properties of a single fracture-hole rock specimen using particle flow code 2D (PFC2D) numerical simulation software and through laboratory tests. We analysed the failure behaviours and mechanical properties of the rock specimen with a single fracture-hole specimen under different fracture angles. The failure modes of single fractured rock samples with different fracture angles were revealed. The fracture propagation and stress evolution of the rock specimen with a single fracture-hole under different fracture angles were investigated. The experimental results shown that the peak strength, peak strain, elastic modulus, initial fracture stress, and damage stress of the single fracture-hole rock specimen with different fracture angles were significantly less than those of the intact rock specimen. Moreover, fracture hole defects accelerated the generation of fractures and promote the failure of the rock specimen. The failure modes were divided into Y, inverted Y, and V types. Before the rock specimen fractures, the stress concentration area was mainly distributed at both ends of the fracture. The stress concentration area at both ends of the fracture gradually decreased, and the stress concentration area near the hole gradually increased as the fracture angle increased. By experiments, the acoustic emission of the model had gone through three stages: initial, steady growth, and rapid decline. The size of the inclination angle affected the number of acoustic emission hits and the generation of acoustic emission signals. Failure behaviours of the rock specimen with a single fracture-hole were systematically investigated, which could promoted the development of fracture rock mechanics and improved the understanding of instability failure mechanism in rock engineering, such as nuclear wasted treatment engineering and deep underground engineering.