Synthesis of 3,4,5-Trisubstituted 1,2,4-Triazoles via I2-Catalyzed Cycloaddition of Amidines with Hydrazones.

A general and practical method for the construction of various 3,4,5-trisubstituted 1,2,4-triazoles via I2-catalyzed cycloaddition of N-functionalized amidines with hydrazones is reported. This strategy features cheap and readily available catalyst and starting materials, broader substrate scope, and moderate-to-good yields. The mechanism study shows that the existence of hydrogen on the nitrogen of hydrazones is crucial for this transformation.

Cycloaddition of N-arylnitrones with donor-acceptor oxiranes via C-C bond cleavage to construct 1,5,2-dioxazinanes.

Highly functionalized 1,5,2-dioxazinanes could be smoothly produced via a Sc(OTf)3-catalyzed chemoselective [3 + 3] cycloaddition of various N-arylnitrones with a series of donor-acceptor oxiranes. This reaction involves in situ generation of 1,3-dipoles through Sc(OTf)3-catalyzed C-C bond cleavage of oxiranes and moderate to high yields were obtained for most substrates. This transformation features C-C bond cleavage of donor-acceptor oxiranes, accessible starting materials and mild reaction conditions.

Cu(OAc)2-catalyzed three-component cycloaddition of malonates, nitrosoarenes and alkenes: access to isoxazolidines.

The Cu(OAc)2-catalyzed one-pot three-component cycloaddition of malonates, nitrosoarenes and alkenes is described. A wide range of isoxazolidines could be obtained in moderate to excellent yields via this method. Mechanistic investigations indicated that the key step in this catalytic system is the straightforward formation of nitrone intermediates through the Cu(OAc)2-catalyzed reaction of malonates with nitrosoarenes.

A large-scale dataset for end-to-end table recognition in the wild.

Table recognition (TR) is one of the research hotspots in pattern recognition, which aims to extract information from tables in an image. Common table recognition tasks include table detection (TD), table structure recognition (TSR) and table content recognition (TCR). TD is to locate tables in the image, TCR recognizes text content, and TSR recognizes spatial & ontology (logical) structure. Currently, the end-to-end TR in real scenarios, accomplishing the three sub-tasks simultaneously, is yet an unexplored research area. One major factor that inhibits researchers is the lack of a benchmark dataset. To this end, we propose a new large-scale dataset named Table Recognition Set (TabRecSet) with diverse table forms sourcing from multiple scenarios in the wild, providing complete annotation dedicated to end-to-end TR research. It is the largest and first bi-lingual dataset for end-to-end TR, with 38.1 K tables in which 20.4 K are in English and 17.7 K are in Chinese. The samples have diverse forms, such as the border-complete and -incomplete table, regular and irregular table (rotated, distorted, etc.). The scenarios are multiple in the wild, varying from scanned to camera-taken images, documents to Excel tables, educational test papers to financial invoices. The annotations are complete, consisting of the table body spatial annotation, cell spatial & logical annotation and text content for TD, TSR and TCR, respectively. The spatial annotation utilizes the polygon instead of the bounding box or quadrilateral adopted by most datasets. The polygon spatial annotation is more suitable for irregular tables that are common in wild scenarios. Additionally, we propose a visualized and interactive annotation tool named TableMe to improve the efficiency and quality of table annotation.

Synthesis of orthogonal push-pull chromophores via click reaction of arylynamines.

Herein, we report a catalyst-free 'click' reaction: metal-free [2 + 2] cycloaddition-retro-electrocyclisation (CA-RE) of arylynamines with the sluggish acceptor tetracyanoquinodimethane (TCNQ) to provide orthogonal electron-push-pull light-harvesting small molecules: N-heterocyclic dicyanoquinodimethane-substituted methylene malononitriles. Ynamines are reactive alkynes and tend to induce over-reactions with the CA-RE adducts. The reactivity of arylynamines was balanced properly by ensuring the electron-density of the nitrogen atom was delocalised more over the aromatic rings than the triple bond.

mtTB: A Web-Based R/Shiny App for Pulmonary Tuberculosis Screening.

Pulmonary tuberculosis caused by Mycobacterium tuberculosis remains a global issue. However, the diagnosis of active pulmonary tuberculosis (TB) remains a challenge in the clinic. Small non-coding RNAs are potential diagnostic biomarkers for pulmonary tuberculosis. However, the current normalization methods are not stable and usually fail to reliably detect differentially expressed sncRNAs. To identify reliable biomarkers for pulmonary tuberculosis screening, we utilized the ratio-based method on the newly discovered mitochondria-derived small RNAs in human peripheral blood mononuclear cells. The prediction model of seven mtRNA biomarkers noteworthily enables the discrimination between pulmonary tuberculosis patients and controls in discovery (AUC = 0.906, 23 patients) and independent validation cohort (AUC = 0.968, 20 patients). Moreover, we present mtTB (https://tuberculosis.shinyapps.io/mtTB/), a novel R Graphical User Interface (GUI) that provides reliable biomarkers for the feasibility of blood-based screening, and produce a more accurate tool for pulmonary tuberculosis diagnosis in real clinical practice.

Total synthesis of (-)-brazilane via a lipase-catalyzed desymmetrisation reaction.

Herein, we described the asymmetric total synthesis of (-)-brazilane, an optically active natural product. The key steps of this synthetic approach are a lipase-catalyzed desymmetrisation reaction of a prochiral diol using vinyl acetate to prepare a chiral primary alcohol and a trifluoroacetic acid-catalyzed one pot intramolecular tandem Prins/Friedel-Crafts reaction used to construct the cis-fused chromane and indane framework.[Formula: see text].

Access to highly functionalized imidazolones bearing α-amino acid esters via KOH-promoted annulation of amidines, nitrosoarenes and malonic esters.

An efficient approach to obtain highly functionalized imidazolones bearing α-amino acid esters through KOH-mediated one-pot three-component annulation of amidines, nitrosoarenes and malonic esters is reported. This reaction features broad substrate scope, a cheap and readily available promoter, good to high yields for most substrates and mild reaction conditions. The mechanism study shows that the KOH-mediated formation of the imine intermediate via the reaction of nitrosoarenes with malonic esters is a key step.

Enantioselective Cascade Biocatalysis for Deracemization of Racemic ß-Amino Alcohols to Enantiopure (S)-ß-Amino Alcohols by Employing Cyclohexylamine Oxidase and ω-Transaminase.

Optically active ß-amino alcohols are very useful chiral intermediates frequently used in the preparation of pharmaceutically active substances. Here, a novel cyclohexylamine oxidase (ArCHAO) was identified from the genome sequence of Arthrobacter sp. TYUT010-15 with the R-stereoselective deamination activity of ß-amino alcohol. ArCHAO was cloned and successfully expressed in E. coli BL21, purified and characterized. Substrate-specific analysis revealed that ArCHAO has high activity (4.15 to 6.34 U mg-1 protein) and excellent enantioselectivity toward the tested ß-amino alcohols. By using purified ArCHAO, a wide range of racemic ß-amino alcohols were resolved, (S)-ß-amino alcohols were obtained in >99 % ee. Deracemization of racemic ß-amino alcohols was conducted by ArCHAO-catalyzed enantioselective deamination and transaminase-catalyzed enantioselective amination to afford (S)-ß-amino alcohols in excellent conversion (78-94 %) and enantiomeric excess (>99 %). Preparative-scale deracemization was carried out with 50 mM (6.859 g L-1 ) racemic 2-amino-2-phenylethanol, (S)-2-amino-2-phenylethanol was obtained in 75 % isolated yield and >99 % ee.

High throughput solid-phase screening of bacteria with cyclic amino alcohol deamination activity for enantioselective synthesis of chiral cyclic ß-amino alcohols.

OBJECTIVES: To screening of bacteria with cyclic amino alcohol deamination activity for enantioselective synthesis of chiral cyclic ß-amino alcohols. RESULTS: A new strain named Arthrobacter sp. TYUT010-15 with the (R)-selective deamination activity of cyclic ß-amino alcohol has been isolated from nature via a high throughput solid-phase screening method. The reaction conditions of TYUT010-15 were optimized. Using the resting cell of TYUT010-15 as the catalyst, kinetic resolution of trans-2-aminocyclopentanol, trans-2-aminocyclohexanol and cis-1-amino-2-indanol was carried out to afford (1S, 2S)-trans-2-aminocyclopentanol, (1S, 2S)-trans-2-aminocyclohexanol and (1R, 2S)-cis-1-amino-2-indanol in > 99% ee and 49.6-50% conversion. Four aromatic ß-amino alcohols and two amines were also resolved, (S)-ß-amino alcohols and (R)-amines were obtained in > 99% ee. Preparation experiment was conducted with 200 mM (23.2 g L-1) racemic trans-2-aminocyclohexanol, yielding the desired (1S, 2S)-trans-2-aminocyclohexanol in 40% isolated yield, > 99% ee and 5.8 g L-1 d-1 space time yields. CONCLUSIONS: This study provides a high throughput solid-phase method for screening of bacteria with cyclic amino alcohol deamination activity and a first example for practical preparation of chiral cyclic ß-amino alcohol by Arthrobacter sp. TYUT010-15.

The First Total Synthesis of (±)-Methyl Salvianolate A Using a Convergent Strategy.

Herein, a convergent, practicable and first total synthesis of the natural product, (±)-methyl salvianolate A, is reported. The key features of the approach are the use of a Horner⁻Wadsworth⁻Emmons reaction and the protection of multiple hydroxyls using silyl protecting groups. The employment of the readily removable silyl protecting groups allows the synthesis of (±)-methyl salvianolate A and its derivatives on a reasonably large scale.

Formal Synthesis of (+)-Phomactin A.

A concise formal synthesis of (+)-phomactin A has been achieved. The key features of this synthetic strategy involve a one-pot Prins/Conia-ene cyclization protocol for the construction of the highly functionalized 1-oxadeclin core (AB ring) and a late-stage direct γ-hydroxylation of enone for the installation of the C ring.

Catalytic Enantioselective Synthesis of 3,4-Polyfused Oxindoles with Quaternary All-Carbon Stereocenters: A Rh-Catalyzed C-C Activation Approach.

The first Rh-catalyzed enantioselective synthesis of a 3,4-polyfused oxindole ring system enabled by carboacylation of acrylic amides based on C-C activation is reported. This transformation provides a new entry to access 3,4-polyfused oxindoles bearing quaternary stereocenters. Tri- to pentacyclic 3,4-fused oxindoles were asymmetrically generated in good yields (up to 95%) with good to excellent enantioselectivity (88%-97% ee). Application in the first total synthesis of xylanigripones A was completed in 6 steps with a 14% overall yield.

Stereoselective total synthesis of (-)-(6S,2'R)-cryptocaryalactone.

We described a novel stereoselective total synthesis of (-)-(6S,2'R)-cryptocaryalactone, a natural product containing syn/anti-6,8-diol/5,6-dihydro-2H-pyran-2-one unit. The approach, which characterised a highly diastereoselective chelation-controlled Mukaiyama aldol reaction of a benzyl-protected aldehyde and a Yamaguchi lactonisation of a δ-hydroxy-trans-α,ß-unsaturated carboxylic acid, is an alternative synthetic strategy towards cryptocaryalactones.

Asymmetric Total Synthesis of Ieodomycin B.

Ieodomycin B, which shows in vitro antimicrobial activity, was isolated from a marine Bacillus species. A novel asymmetric total synthetic approach to ieodomycin B using commercially available geraniol was achieved. The approach involves the generation of 1,3-trans-dihydroxyl at C-3 and C-5 positions via a Crimmins-modified Evans aldol reaction and a chelation-controlled Mukaiyama aldol reaction of a p-methoxybenzyl-protected aldehyde, as well as the generation of a lactone ring in a deprotection-lactonization one-pot reaction.

Enantioselective Synthesis of the ABC-Tricyclic Core of Phomactin A by a γ-Hydroxylation Strategy.

An enantioselective synthesis of the ABC-tricyclic furanochroman core of phomactin A has been accomplished by a γ-hydroxylation approach. The C ring was established by γ-hydroxylation of an α-enone. The regioselectivity was optimized by using a strong base with an oxophilic cation (t-BuLi) and a bulky oxygen donor (Davis reagent), which afforded the γ-hydroxylation product selectively in 63% yield.

Construction of the tricyclic furanochroman skeleton of phomactin A via the Prins/Conia-ene cascade cyclization approach.

A substrate-controlled asymmetric Prins/Conia-ene cascade cyclization has been developed with In(OTf)(3) in CH(3)CN from 0 to 70 °C. These conditions afforded very good yields of the 1-oxadecalin product in one pot and effectively suppressed the racemization of the 1-oxadecalin product with almost no enantiomeric excess (ee) loss. This cascade cyclization has been successfully employed for the construction of the highly functionalized 1-oxadecalin unit of phomactin A with an acyclic ß-keto ester and an alkynal as the substrates via a one-pot operation (66% yield, single diastereomer). The 1-oxadecalin moiety has been readily converted to the tricyclic furanochroman skeleton of phomactin A via the epoxidation/dealkoxycarbonylation protocol under very mild conditions with 52% yield in three steps.