An Intramolecular Schmidt Reaction of δ-Azido N-Acylbenzotriazoles.

A Lewis acid promoted intramolecular Schmidt reaction of N-acylbenzotriazoles with alkyl azides was designed and realized. The benzotriazole was not only employed as an efficient activator for initiating the Schmidt rearrangement but also used as a powerful terminator for the subsequent nucleophilic trapping of the isocyanate ion and/or N-acyliminium ion from the rearrangement. Thirteen δ-azido N-acylbenzotriazoles were investigated, and the conversion afforded the desired benzotriazole-1-carboxamides and lactams with good to excellent yields.

Rhodium-catalysed diastereo- and enantio-selective cyclopropanation of α-boryl styrenes.

A rhodium-catalyzed diastereo- and enantio-selective cyclopropanation of α-boryl styrenes with α-diazoarylacetates was established. Rh2(S-PTTL)4 (0.2 mol%) was found to be effective for the conversion, and 21 diastereopure cyclopropylboronates were prepared in high yields with excellent enantioselectivity (ee up to 99%).

Detection and characterization of anterior loop, accessory mental foramen, and lateral lingual foramen by using cone beam computed tomography.

STATEMENT OF PROBLEM: The presence of an anterior loop (AL), accessory mental foramen (AMF), or lateral lingual foramen (LLF) adds complexity to the mental foraminal region, and consequently, implant placement in this region can damage the nerves and blood vessels if the structures are not carefully identified. PURPOSE: The purpose of this retrospective study was to evaluate the characteristics of the AL, AMF, and LLF to provide recommendations for surgeons operating in the mandibular mental foraminal region. MATERIAL AND METHODS: Reconstructed cone beam computed tomography (CBCT) images in 306 Southern Chinese patients were retrospectively analyzed. The prevalence of the anterior loop was assessed, and the anterior loop length (ALL) was measured from the most anterior point of the mental foramen to the most mesial part of the anterior loop. The prevalence, location of the AMF as related to the mental foramen, and adjacent teeth were analyzed. Additionally, the distance from the mental foramen to AMF centers were measured. The prevalence, diameter, and location of the LLF were evaluated. The chi-square test was used for prevalence analysis (α=.05). RESULTS: Anterior loops were identified in 67.8% of the 612 hemimandibles, with a mean length of 3.3 ±1.2 mm, ranging from 1.2 to 7.3 mm. A total of 5.56% of the hemimandibles had an ALL ≥5 mm, and male patients had a statistically longer loop length (P=.006). The ALL on the right side was found to be statistically longer than that on the left side (P=.002). No statistically significant differences in the ALL were found among different age groups (P=.124). AMFs were observed in 10.5% of the patients, with most located in the posterosuperior position of the mental foramen. The mean distance between the center of the AMF and the mental foramen was 5.1 ±1.4 mm. LLFs presented in 69.9% of patients, with 74.0% located in the premolar region. The mean vertical diameter of the LLF was 0.9 ±0.3 mm, and the mean distance from LLF to the mandibular inferior border was 7.1 ±1.9 mm. CONCLUSIONS: This study revealed that ALs, AMFs, and LLFs occurred often in the Southern Chinese population. Identifying the presence of the AL, AMF, and LLF is important before surgery in the mental foraminal region.

Synthesis of Isoindoles from Intramolecular Condensation of Benzyl Azides with α-Aryldiazoesters.

Rh-catalyzed intramolecular condensation of the benzyl azides with α-aryldiazoesters was explored. The reaction proceeded through the nucleophilic attack of the organic azide onto a rhodium carbenoid, while releasing nitrogen gas, affording the α-imino esters as the primary product. Tautomerization of the imino esters efficiently gave 13 desired isoindoles with good to excellent yields.

Schmidt Reaction of ω-Azido Valeryl Chlorides Followed by Intermolecular Trapping of the Rearrangement Ions: Synthesis of Assoanine and Related Pyrrolophenanthridine Alkaloids.

The Schmidt reaction of ω-azido valeryl chlorides in the presence of an additional nucleophile was explored. The arenes, alcohols, and amines were demonstrated as the intermolecular trapping reagents for isocyanate ion and N-acyliminium ion from the Schmidt rearrangement, affording the corresponding products with moderate to excellent yields. Two 2-oxoindoles from the reaction were successfully converted into four natural alkaloids, namely, assoanine, anhydrolycorine, oxoassoanine, and anhydrolycorinone.

Tf2O-Promoted Intramolecular Schmidt Reaction of the ω-Azido Carboxylic Acids.

A designed Tf2O-promoted intramolecular Schmidt reaction of 2-substituted ω-azido carboxylic acids was demonstrated. Tf2O was used as an activation reagent for the carboxylic acid, and ω-azido anhydride was in situ generated, releasing a molecular TfOH, which acted as an acid promoter for the Schmidt process. A series of 2-substituted pyrrolidines was produced and acetylated for better purification. The strategy was also efficient for conversion of a 4-substituted ω-azido carboxylic acid to the tricyclic lactam.

Label-free based quantitative proteomic analysis identifies proteins involved in the testis maturation of Bactrocera dorsalis (Hendel).

Complex structural and biochemical processes take place in insect testis maturation, but the mechanisms by which functional proteins induce and regulate male fertility are unknown. Proteomics has been widely used to identify functional proteins involved in such complex physiological processes. In this study, we performed a label-free based quantitative proteomic analysis of developing testis of Bactrocera dorsalis with the aim of shedding light on spermatogenesis, sperm formation and also tissue development. A total of 1912 reliable proteins were identified, including 1589, 1705 and 1723 proteins in 1-, 5- and 9-d-old testis, respectively. Most of these proteins (76.68%) were identified by two to ten peptides, and the mean number of peptides was 7.46 with an average sequence coverage of 30.71%. Quantitative proteomic analysis showed that there were 141 and 111 proteins which were abundant in the 5- and 9-d-old testis, respectively. The Gene Ontology (GO) and Clusters of Orthologous Groups (COG) analyses showed that many of these proteins function in cellular and metabolic processes, including binding and catalytic activities in molecular function analysis, and energy production, cell division, and cell motility in COG analysis. Potential functional proteins, such as heat shock proteins, glutathione S-transferase, transferrin, metalloproteinase and energy metabolism-related proteins, were found to be abundant in the intermediate and sexual maturity stages of testis. The findings in this study help us to better understand the molecular mechanisms behind testis development and spermatogenesis, which is essential for manipulating male fertility for ecological regulation and potential control of this species.

Preparation of Optically Active cis-Cyclopropane Carboxylates: Cyclopropanation of α-Silyl Stryenes with Aryldiazoacetates and Desilylation of the Resulting Silyl Cyclopropanes.

Optically active cis-cyclopropane carboxylates are prepared via the Rh2(S-PTAD)4-catalyzed cyclopropanation of α-silyl styrenes with aryl diazoacetates followed by desilylation of the resulting silyl cyclopropane carboxylates. The conjugation of the aryl ring with C═C bond and π stacking are proposed for the stereoselectivity of cyclopropanation, and configuration inversion is observed with the desilylation process.

Asymmetric Intramolecular Desymmetrization of meso-α,α'-Diazido Alcohols with Aryldiazoacetates: Assembly of Chiral C3 Fragments with Three Continuous Stereocenters.

The chiral Cu-complex-catalyzed intramolecular interception of meso-α,α'-diazido alcohols with aryldiazoacetates is explored. Most of the enantioenriched α-imino esters with three continuous stereocenters are produced with good to excellent yield and enantioselectivity, and a chiral pocket model is proposed for rationalization of the asymmetric desymmetrization.

Proteomic analysis of Vibrio metschnikovii under cold stress using a quadrupole Orbitrap mass spectrometer.

Vibrio metschnikovii is a food-borne pathogen found in seafood worldwide. We studied the global proteome responses of V. metschnikovii under cold stress by nano-flow ultra-high-performance liquid chromatography coupled to a quadrupole Orbitrap mass spectrometer. A total of 2066 proteins were identified, among which 288 were significantly upregulated and 572 were downregulated. Functional categorization of these proteins revealed distinct differences between cold-stressed and control cells. Quantitative reverse transcription polymerase chain reaction analysis was also performed to determine the mRNA expression levels of seventeen cold stress-related genes. The results of this study should improve our understanding of the metabolic activities of cold-adapted bacteria and will facilitate a better systems-based understanding of V. metschnikovii.

Intramolecular Schmidt reaction of acyl chlorides with alkyl azides: preparation of pyrrolizine by intramolecular capture of intermediates with alkenes or alkynes.

The preparation of substituted pyrrolizines through the Schmidt reaction of acyl chlorides with alkyl azides has been realized. Intramolecular capture of the isocyanate ion and N-acyliminium ion intermediates from the Schmidt process with alkene or alkyne units was achieved, and the efficiency of the conversion with respect to ring construction and bond formation was demonstrated.

Proteomic analysis of rat plasma with experimental autoimmune uveitis based on label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Uveitis is a severe autoimmune eye disease that can cause intraocular inflammation even lead to severe vision loss, and the occurrence of uveitis can be closely associated with abnormal expression of proteins. However, the abnormally expressed proteins involved in uveitis are not well identified. Using liquid chromatography-tandem mass spectrometry technique, we examined the alterations in proteomic expression profiling in rat plasma specimens related to experimental autoimmune uveitis (EAU) versus normal samples. In addition, the experimental verification was further performed using enzyme-linked immunosorbent assay (ELISA) for abnormally expressed proteins in EAU rat plasma. The results indicate that 62 proteins were upregulated and 106 proteins were downregulated in plasma from EAU rats compared with those in saline-treated samples. In the meantime, we observed that the plasma level of complement component 3 in EAU rats was upregulated versus saline-treated rats (from 92.32µg/mL to 168.92µg/mL), whereas the level of interleukin-1 receptor accessory protein was downregulated (from 1120.97pg/mL to 798.39pg/mL), and these results were highly in agreement with those of mass spectrometry determination. Taken together, our results indicate that liquid chromatography-tandem mass spectrometry analysis possesses a good resolution for peptides in plasma, and the findings will provide the baseline plasma dataset for EAU rats and the relevant information can contribute to future studies on the understanding the mechanism of uveitis.

Versatile characterization of glycosylation modification in CTLA4-Ig fusion proteins by liquid chromatography-mass spectrometry.

CTLA4-Ig is a highly glycosylated therapeutic fusion protein that contains multiple N- and O-glycosylation sites. Glycosylation plays a vital role in protein solubility, stability, serum half-life, activity, and immunogenicity. For a CTLA4-Ig biosimilar development program, comparative analytical data, especially the glycosylation data, can influence decisions about the type and amount of animal and clinical data needed to establish biosimilarity. Because of the limited clinical experience with biosimilars before approval, a comprehensive level of knowledge about the biosimilar candidates is needed to achieve subsequent development. Liquid chromatography-mass spectrometry (LC-MS) is a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. In this report, an in-depth characterization of glycosylation of a candidate biosimilar was carried out using a systematic approach: N- and O-linked glycans were identified and electron-transfer dissociation was then used to pinpoint the 4 occupied O-glycosylation sites for the first time. As the results show, the approach provides a set of routine tools that combine accurate intact mass measurement, peptide mapping, and released glycan profiling. This approach can be used to comprehensively research a candidate biosimilar Fc-fusion protein and provides a basis for future studies addressing the similarity of CTLA4-Ig biosimilars.

Catalytic enantioselective desymmetrization of 1,3-diazido-2-propanol via intramolecular interception of alkyl azides with diazo(aryl)acetates.

The first catalytic enantioselective desymmetrization of 1,3-diazido-2-propanol via an intramolecular interception of alkyl azides by Cu-carbenoids has been realized. A wide range of 1,3-diazidoisopropyl diazo(aryl)acetates were converted to cyclic α-imino esters in the presence of bisoxazoline ligand (S,S)-Ph-Box with good to excellent yields, and the enantiomeric excess was up to 97%.

Preparation of enantioenriched γ-substituted lactones via asymmetric transfer hydrogenation of ß-azidocyclopropane carboxylates using the Ru-TsDPEN complex.

The asymmetric transfer hydrogenation of racemic ß-azidocyclopropane carboxylates has been explored. Ru-TsDPEN B is found to be a good catalyst for the formation of enantioenriched γ-lactones through a four-step sequence of azide reduction/cyclopropane ring cleavage/ketone transfer hydrogenation/lactonization, and the enantiomeric excess of the lactones was up to 94%.

Proteomics analysis of adult testis from Bombyx mori.

The development of the testis involves a large number of tissue-specific proteins, possibly because the sperms in it are the most divergent of all cell types. In this study, LC-MS/MS was employed to investigate the protein compositions of the adult testis of silkworm. A total of 14,431 peptides were identified in the adult testis of Bombyx mori, which were matched to 2292 proteins. Thirty-two HSPs constitute a group of most abundant proteins in the adult testis, suggesting that they are critical for the development, differentiation, and survival of germ cells. Other proteins in this analysis were also involved in testis-specific processes mainly including sperm motility, meiosis, germ cell development, and spermatogenesis. The data have been deposited to the ProteomeXchange with identifier PXD000909 (http://proteomecentral.proteomexchange.org/dataset/PXD000909).

Intramolecular Schmidt reaction of acyl chlorides with alkyl azides: capture of N-acyliminium ion intermediates with aromatic rings.

Intramolecular Schmidt reaction of acyl chlorides with alkyl azides through N-acyliminium ion intermediates is designed and realized. The intramolecular capture of the intermediates with aromatic rings affords several nitrogen-containing tricyclic skeletons. The important feature of the domino process is the efficiency in bond reorganization and ring formation.

Proteomics of larval hemolymph in Bombyx mori reveals various nutrient-storage and immunity-related proteins.

The silkworm, Bombyx mori, is an important economic insect for its production of silk. The larvae of many lepidopteran insects are major agricultural pests and often silkworm is explored as a model organism for other lepidopteran pest species. The hemolymph of caterpillars contains a lot of nutrient and immune components. In this study, we applied liquid chromatography-tandem mass spectrometry to gain a better understanding of the larval hemolymph proteomics in B. mori. We identified 752 proteins in hemolymph collected from day-4 fourth instar and day-7 fifth instar. Nearly half the identified proteins (49%) were predicted to function as binding proteins and 46% were predicted to have catalytic activities. Apolipophorins, storage proteins, and 30K proteins constituted the most abundant groups of nutrient-storage proteins. Of them, 30K proteins showed large differences between fourth instar larvae and fifth instar larvae. Besides nutrient-storage proteins, protease inhibitors are also expressed very highly in hemolymph. The analysis also revealed lots of immunity-related proteins, including recognition, signaling, effectors and other proteins, comprising multiple immunity pathways in hemolymph. Our data provide an exhaustive research of nutrient-storage proteins and immunity-related proteins in larval hemolymph, and will pave the way for future physiological and pathological studies of caterpillars.

Cyclohexanones by Rh-mediated intramolecular C-H insertion.

Some long chain α-aryl α-diazo ketones under Rh catalysis cyclize efficiently to the corresponding cyclohexanones. This is in marked contrast to the cyclizations of α-diazo ß-ketoesters, which consistently deliver cyclopentanone products.