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Organocatalysis is the use of non-stoichiometric amounts of low-molecular-weight organic molecules made up of C, H, N, O, S, and P to accelerate stereoselective chemical transformations. Despite having a long history, the use of small organic molecules as chiral catalysts in enantioselective synthesis has only recently intrigued scientists interest. However, in synthetic and medicinal chemistry, there has been a resurgence of interest in performing asymmetric synthesis of a variety of important targets by utilizing an organocatalytic approach as a leading reaction. The development of an asymmetric protocol for the synthesis of enantioenriched molecules of therapeutic relevance is crucial in the development of new drug candidates. Modern asymmetric catalysis is based on three pillars: (i) biocatalysts (i.e., enzymes), (ii) transition metal catalysis, and (iii) organocatalysis. Among these catalytic systems, organocatalysis has become the most flourishing field within the field of a catalytic regime that offers many significant benefits to synthetic and medicinal chemists. In contrast to many metal-based catalytic models, most organocatalysts have a high tolerance capability for air and moisture, easy availability, easy handling, non-toxic and enantiomeric purity, etc. They are often derived from natural resources of high enantiomeric virtue with the desired stereocentre or easily synthesized in the laboratory in some simple synthetic operations. This perspective aims to draw readers' attention to the power of asymmetric organocatalysis in assembling glycosyl donors and acceptors in the synthesis of biologically significant stereodefined O-glycosides. Glycosylation is a fundamental chemical transformation and is ubiquitous in both nature and chemical laboratories. In nature, the glycosylation processes are carried out by enzyme catalysis. We were interested in portraying the recent impressive progress achieved by the scientific community in the field of chemical glycosylation, specifically O-glycosylation. Poly-functionalized sugar moieties offer many opportunities to discover new drug candidates in which the modification of aglycone through the glycosylation process is a key reaction. [ABSTRACT FROM AUTHOR]

Bone fracture is a severe health concern; therefore, understanding the causes of bone fracture are crucial. This paper investigates the microstructure and fracture behaviour of cadaveric cortical bone of two different groups (Young, n= 6; Aged, n=7). The microstructure is obtained from µ-CT images, and the material parameters are measured with nanoindentation. Fracture behaviour in transverse and longitudinal orientations is investigated experimentally and numerically. The results show that the Haversian canal (HC) size increases and the osteon wall thickness (OWT) decreases significantly in the aged group, whereas a nonsignificant difference is found in tissue properties. The crack initiation (J ic) and crack growth (J grow) toughness of the aged group are found to be significantly lower (p<0.01) than the young group in the transverse orientation; however, for the longitudinal orientation, only the value of J ic in the aged group is found significantly lower. Further, a 4-phase XFEM (based on micro-CT image) model is developed to investigate the crack propagation behaviour in both orientations. For the transverse orientation, results show that in the aged group, the crack initially follows the cementline and then penetrates the osteon, whereas, in the young group, it propagates along the cementline. These results are in agreement with experimental results where the decrease in J grow is more significant than the J ic in the aged group. This study suggests that ageing leads to a larger HC and reduced OWT, which weakens the crack deflection ability and causes fragility fracture. Further, the XFEM results indicate that the presence of a small microcrack in the vicinity of a major crack tip causes an increase in the critical stress intensity factor. [ABSTRACT FROM AUTHOR]

A novel, one-pot, three-component coupling (3-CCR) reaction of aromatic aldehydes, β-naphthol, and 6-amino-1,3-dimethyl uracil in a deep eutectic solvent (DES) has been developed as a highly efficient and selective method for the expedient synthesis of the densely functionalized 8,10-dimethyl-12-phenyl-8,12-dihydro-9H-benzo[5,6]chromeno[2,3-d]pyrimidine-9,11(10H)-dione framework in synthetically pleasing yield. The devised protocol adeptly harnesses the versatility of DESs, resulting in a straightforward, cost-effective, resilient, and environmentally sustainable synthetic approach. The resulting cascade adduct exhibits noteworthy antiproliferative activity against a variety of cancer cell lines, thereby showing promise as a potential anticancer drug candidate for breast and hepatocellular carcinoma with moderate to good IC50 values. The most potent compounds in the synthesized library, 4m and 4l, exhibit highly potent cytotoxicity against HepG2 and MCF7 cancer cell lines, with notable IC50 values of 46.39 and 28.21 μM, respectively. The present findings are corroborated by computational and molecular docking studies. The density functional theory (DFT) calculations underscore the pivotal role of the naphthyl ring in orchestrating the success of this intricate domino process in delivering the anticipated scaffolds in reasonable yields. [ABSTRACT FROM AUTHOR]

• This study investigates the effect of type 2 diabetes on time dependent properties of trabecular bone using stress relaxation and dynamic mechanical analysis under compression loading. • Correlation of viscoelastic properties with microstructural parameters and biochemical properties are established. • Type 2 diabetes causes degradation storage modulus and initial stress as compared non type 2 diabetes. • The viscoelastic properties are independent of type 2 diabetes. • Amount of stress relaxed during the hold period is related to its mineral and matrix content. Type 2 diabetes (T2D) is a well-known disease that impaired bone mechanical properties and increases the risk of fragility fracture. The bone tissue is a viscoelastic material that means the loading rate determines its mechanical properties. This study investigates the impact of T2D on the viscoelastic properties of human bone and its association with microstructure and biochemical properties. Viscoelasticity is an important mechanical property of bone and for this the interaction of individual constituents of bone plays an important role. The viscoelastic nature of bone can be affected by aging and diseases, which can further influence its deformation and damage behavior. The present study investigated the effects of T2D on the viscoelastic behavior of trabecular bone. The femoral heads of T2D (n = 26) and non-T2D (n = 40) individuals with hip fragility fractures were collected for this investigation. Following the micro-CT scanning of all bone samples, the stress relaxation and dynamic mechanical analysis (DMA) tests were performed to quantify the viscoelasticity of bone. Further, a correlation analysis was performed to investigate the effects of alteration in bone microstructural and biochemical parameters on viscoelasticity. The stress relaxation and frequency sweep responses of T2D and non-T2D trabecular bone specimens were not found significantly different. However, the storage modulus, initial stiffness, and initial stress were found lower in T2D bone. The significant correlation of percentage stress relaxed is obtained between the mineral content (r = - 0.52, p-value = 0.003), organic content (r = 0.40, p-value = 0.02), and mineral-to-matrix ratio (r = - 0.43, p-value = 0.009). Further, storage and loss modulus were correlated with bone volume fraction (BV/TV) for both groups. The stress relaxation and frequency sweep characteristics were not found significantly connected with the other chemical, structural, or clinical parameters. This study suggests that T2D does not affect the time-dependent response of human femoral trabecular bone. The viscoelastic properties are positively correlated with organic content and negatively correlated with mineral content. [ABSTRACT FROM AUTHOR]

The asymmetric reactions of imines continued to attract the attention of the scientific community for decades. However, the stereoselective reactions of N-phosphonyl/phosphoryl imines remained less explored as compared to other N-substituted imines. The chiral auxiliary-based asymmetric-induction strategy with N-phosphonyl imines could effectively generate enantio- and diastereomeric amine, α,β-diamine, and other products through various reactions. On the other hand, the asymmetric approach for the generation of chirality through the utilization of optically active ligands, along with metal catalysts, could be successfully implemented on N-phosphonyl/phosphoryl imines to access numerous synthetically challenging chiral amine scaffolds. The current review critically summarizes and reveals the literature precedence of more than a decade to highlight the major achievements existing to date that can display a clear picture of advancement as well drawbacks in this area. [ABSTRACT FROM AUTHOR]

Abstract: Intramolecular Diels–Alder reaction of trienones embedded in a sugar derivative with or without Me substituents on the diene part has been investigated for synthesis of hydrindanes with angular oxygen functionality. One of these adducts has been transformed to a functionalized bicyclic skeleton present in galiellalactone. [Copyright &y& Elsevier]

Abstract: An efficient stereoselective approach to the construction of a hydrindane derivative having a bridged lactone is described toward the synthesis of the sesquiterpenes of the seco-prezizaane family. The key step involves RO-RCM of a norbornene derivative. [Copyright &y& Elsevier]

A general approach for the synthesis of fused cyclic systems containing medium-sized rings (7-9) has been developed. The key steps involve a diastereoface-selective Diels-Alder reaction of the dienophiles 4a-d attached to a furanosugar with cyclopentadiene and ring opening (ROM)-ring closing metathesis (RCM) of the resulting norbornene derivatives 10a-d and lla-d. Diels-Alder reaction of the dienophiles 4a-d with cyclopentadiene in the absence of a catalyst produced 10a-d as the major product arising through addition of the diene to the unhindered Si-face. The most interesting and new aspect of the Diels-Alder reaction of these dienophiles is the accessibility of the Re-face that was blocked by the alkenyl chains under Lewis acid catalysis producing the diastereoisomers 11a-d exclusively. The reversal of facial selectivity from an uncatalyzed reaction to a catalyzed one is unprecedented. The observed stereochemical dichotomy is attributed to rotation of the enone moiety along the a bond linking the sugar moiety during formation of the chelate 13. This makes the Re-face of the enone moiety in 4a-d unhindered. Diels-Alder reaction of the carbocyclic analogue 15 under Lewis acid catalysis produced a 1:1 mixture of the adducts 16 and 17 confirming the participation of sugar ring oxygen in chelate formation. Finally ROM-RCM of 10a-d and 11a-d with Grubbs' catalyst afforded the cis-syn-cis and cis-anti-cis bicyclo-annulated sugars 21a-d and 23a-d, respectively, containing 7-9 membered rings. [ABSTRACT FROM AUTHOR]

Type-2 diabetic (T2D) and osteoporosis (OP) suffered patients are more prone to fragile fracture though the nature of alteration in areal bone mineral density (aBMD) in these two cases are completely different. Therefore, it becomes crucial to compare the effect of T2D and OP on alteration in mechanical and structural properties of femoral trabecular bone. This study investigated the effect of T2D, OP, and osteopenia on bone structural and mechanical properties using micro-CT, nanoindentation and compression test. Further, a nanoscale finite element model (FEM) was developed to predict the cause of alteration in mechanical properties. Finally, a damage-based FEM was proposed to predict the pathological related alteration of bone's mechanical response. The obtained results demonstrated that the T2D group had lower volume fraction (−18.25%, p = 0.023), young's modulus (−23.47%, p = 0.124), apparent modulus (−37.15%, p = 0.02), and toughness (−40%, p = 0.001) than the osteoporosis group. The damage-based FE results were found in good agreement with the compression experiment results for all three pathological conditions. Also, nanoscale FEM results demonstrated that the elastic and failure properties of mineralised collagen fibril decreases with increase in crystal size. This study reveals that T2D patients are more prone to fragile fracture in comparison to OP and osteopenia patients. Also, the proposed damage-based FEM can help to predict the risk of fragility fracture for different pathological conditions. [ABSTRACT FROM AUTHOR]

Abstract: A novel Cu(I)-catalyzed photochemical reaction of diethyl ether with vicinal diols and their ketals is reported. The most remarkable feature is the transformation of 1,2-diols and their ketals to acetals of acetaldehyde under totally neutral condition without using acetaldehyde. [Copyright &y& Elsevier]

Type 2 diabetes mellitus (T2DM) adversely affects the normal functioning, intrinsic material properties, and structural integrity of many tissues, including bone. It is well known that the clinical utility of areal bone mineral density (aBMD) is limited to assess bone strength in individuals with T2DM. Therefore, there is a need to explore new diagnostic techniques that can better assist and improve the accuracy of assessment of bone tissue quality. The present study investigated the link between bone and fingernail material/compositional properties in type 2 diabetes mellitus (T2DM). For that, femoral head and fingernail samples were obtained from twenty-five adult female patients (with/without T2DM) with fragility femoral neck fractures undergoing hemi/total hip arthroplasty. Cylindrical cores of trabecular bone were subjected to micro-CT, and lower bone volume fraction was observed in the diabetic group than the non-diabetic group due to fewer and thinner trabeculae in individuals with T2DM. The material and compositional properties of bone/fingernail were estimated using nanoindentation and Fourier Transform Infrared Spectroscopy, respectively. Both bone/fingernails in T2DM had lower reduced modulus (Er), hardness (H), lower Amide I and Amide II area ratio (protein content), higher sugar-to-matrix ratio, and relatively high carboxymethyl-lysine (CML) content compared with non-diabetic patients. Sugar-to-matrix ratio and relative CML content were strongly and positively correlated with HbA1c for both bone/fingernail. There was a positive correlation between bone and fingernail glycation content. Our findings provide evidence that the degradation pattern of bone and fingernail properties go hand-in-hand in individuals with T2DM. Hence, the fingernail compositional/material properties might serve as a non-invasive surrogate marker of bone quality in T2DM; however, further large-scale studies need to be undertaken. [ABSTRACT FROM AUTHOR]

In order to design a painless and mechanically durable micro syringe-needle system for biomedical applications, the study of insect stingers is of interest because of their elegant structures and functionalities. In the present work, the structure, mechanical properties and the mechanical behavior during insertion of wasp and honeybee stingers have been investigated. The non-invasive imaging tool, micro-computed tomography has been employed to reveal the 3D-structures of wasp and honeybee stingers. A quasi-static nanoindentation instrument was used to measure the nanomechanical properties. Both wasp and honeybee stingers have graded mechanical properties, decreasing along their longitudinal direction starting from the base. The computed tomography images and the measured material properties from nanoindentation were fed into a computational framework to determine the mechanical behavior of the stingers during penetration. The computation results predicted the penetration angle of +10° for the wasp stinger and −6° for the honeybee stinger, which mimics the practical insertion mechanism of both stingers. Based on this understanding, a wasp and honeybee stringer inspired micro syringe-needle design has also been proposed. [ABSTRACT FROM AUTHOR]

The article presents a chemical reaction formula for intramolecular diels- alder route to angularly oxygenated hydrindanes, synthesis of the functionalized bicyclic skeleton present in galiellalactone.

A novel 8-hydroxy quinoline-derived amide receptor, in conjunction with its Cu (II) and Zn (II) complexes, has been strategically developed to function as remarkably efficient fluorescent receptors with a distinct capability for anion sensing. The comprehensive characterization of the synthesized compounds were achieved through UV-Vis, IR, NMR, and HRMS spectroscopic techniques. Among the Cu (II) and Zn (II) complexes, the latter exhibits superior selectivity for anions, specifically dihydrogen phosphate and hydrogen sulfate, as their tetrabutylammonium salts in a 9:1 acetonitrile-water (v/v) mixture. The Cu (II) complex demonstrates enhanced anion binding compared to the amide ligand, albeit with reduced selectivity. Furthermore, the affinity was evaluated using the Benesi-Hildebrand plot. The binding constants and Limit of Detection (LOD) for both complexes were precisely quantified. The Job plot illustrates a clear 1:1 binding interaction between the metal complexes and the guest anions. Significantly, both metal-complex receptors display a broad spectrum of antibacterial activity, against both gram-positive and gram-negative bacteria. It is worth highlighting that the Zn (II) complexed receptor outperforms the Cu (II) complexed receptor, as evidenced by its considerably lower Minimum Inhibitory Concentration (MIC) value against both bacterial strains. [ABSTRACT FROM AUTHOR]

Differential surface anisotropy of different crystals of the same API can have a significant impact on their pharmaceutical performance. The present work investigated the impact of differential surface anisotropy of two plate-shaped crystals of aspirin (form I) on their hygroscopicity, stability and compaction behavior. These crystals differed in their predominant facets (100) and (001) and were coded as AE-100 & E-001. (100) facets exposed polar carbonyl groups which provided hydrophilicity to the facets. In contrast, (001) facets possessed hydrophobicity as they exposed non-polar aryl and methyl groups. Both the samples showed different degradation behavior, at various stability conditions (i.e. 40 °C/75%RH, 30 °C/90%RH and 30 °C/60%RH) and different time intervals. Polar groups of aspirin have been reported to be prone to hydrolysis due to which AE-100 was less stable than E-001. Dynamic vapor sorption (DVS) analysis at different simulated stability conditions also supported this observation, wherein AE-100 showed higher moisture sorption than E-001. Both the samples having similar particle size, shape, surface area and hardness value, showed differences in their compactibility. However, milling narrowed down the predominance of facets and both the milled samples showed similar stability and compaction behavior. This study was also supported by surface free energy determination, molecular modeling and face indexation of unmilled and milled samples. [ABSTRACT FROM AUTHOR]