1,210 results match your criteria expedient synthesis

AgOTf/I-Mediated Cyclization/Cross-Coupling/Isomerization of Enynones with Phosphorus Ylides: An Expedient Route to Stereoselective Synthesis of ()-2-Alkenylfurans.

J Org Chem 2021 Sep 16. Epub 2021 Sep 16.

Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education of China), Hunan Normal University, Changsha 410081, China.

Ag(I)-catalyzed cascade reactions involving enynone cyclization and cross-coupling with phosphorus ylides have been achieved for the first time. Subsequent treatment of the reaction mixture with I afforded the corresponding ()-α-alkenylfurans in 73-95% yields with excellent stereoselectively. A reasonable mechanism has been proposed. Read More

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September 2021

Total syntheses and antiproliferative activities of prenostodione and its analogues.

Org Biomol Chem 2021 Sep 14. Epub 2021 Sep 14.

Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, Coyoacán, Ciudad de México, 04510, Mexico.

A high-yielding total synthesis of the indole alkaloid prenostodione was completed in 4 steps and 44% overall yield from 1-indole-3-carboxylic acid. The expedient syntheses of prenostodiones containing distinct substituents at the position of the phenyl frame underscored the scope of this methodology. The cytotoxic activities of the -butyl esters of prenostodione analogues were tested using six tumor cell lines. Read More

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September 2021

Syntheses of 1H-Indoles, Quinolines, and 6-Membered Aromatic N-Heterocycle-Fused Scaffolds via Palladium(II)-Catalyzed Aerobic Dehydrogenation under Alkoxide-Free Conditions.

Chem Asian J 2021 Sep 7. Epub 2021 Sep 7.

College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea.

Aromatic N-heterocycle-fused scaffolds such as indoles and quinolines are important core structures found in various bioactive natural products and synthetic compounds. Recently, various dehydrogenation methods with the help of alkoxides, known to significantly promote dihydro- or tetrahydro-heterocycles to be oxidized, were developed for the heterocycle synthesis. However, these approaches are sometimes unsuitable due to resulting undesired side reactions such as reductive dehalogenation. Read More

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September 2021

DNA-encoded chemistry technology yields expedient access to SARS-CoV-2 M inhibitors.

Proc Natl Acad Sci U S A 2021 09;118(36)

Center for Drug Discovery, Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX 77030;

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed more than 4 million humans globally, but there is no bona fide Food and Drug Administration-approved drug-like molecule to impede the COVID-19 pandemic. The sluggish pace of traditional therapeutic discovery is poorly suited to producing targeted treatments against rapidly evolving viruses. Here, we used an affinity-based screen of 4 billion DNA-encoded molecules en masse to identify a potent class of virus-specific inhibitors of the SARS-CoV-2 main protease (M) without extensive and time-consuming medicinal chemistry. Read More

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September 2021

Visible-Light-Induced Dearomatization of Indoles/Pyrroles with Vinylcyclopropanes: Expedient Synthesis of Structurally Diverse Polycyclic Indolines/Pyrrolines.

J Am Chem Soc 2021 Aug 16;143(33):13441-13449. Epub 2021 Aug 16.

State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032, China.

Visible-light-induced cycloaddition reactions initiated via energy-transfer processes have recently evolved as powerful methods for the construction of strained cyclic molecules that are not easily accessed using known ground-state synthetic methods. Particularly, the reactions initiated by the excitation of aromatic rings provide an alternative solution to the direct transformations of aromatic feedstocks under the scheme of dearomatization. Vinylcyclopropanes (VCPs) are well-known reagents in radical clock experiments, working as a probe to detect transient radical intermediates. Read More

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Nickel-Catalyzed Selective Decarbonylation of α-Amino Acid Thioester: Aminomethylation of Mercaptans.

J Org Chem 2021 Sep 16;86(17):12148-12157. Epub 2021 Aug 16.

College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.

The nickel-catalyzed aminomethylation of mercaptans has been disclosed that offers efficient and expedient access to synthesize α-aminosulfides. The intramolecular fragment coupling shows excellent chemoselectivity. This transformation shows good functional-group compatibility, tolerates a wide range of electron-withdrawing, electron-neutral, and electron-donating substituents in this process, and can serve as a powerful synthetic tool for the synthesis of α-aminosulfides at a gram scale. Read More

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September 2021

Cationic Cycloheptatrienyl Cyclopentadienyl Manganese Sandwich Complexes: Tromancenium Explored with High-Power LED Photosynthesis.

Organometallics 2021 Aug 27;40(15):2736-2749. Epub 2021 Jul 27.

Institute of General, Inorganic and Theoretical Chemistry, Center for Chemistry and Biomedicine, University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria.

In this contribution, we revisit the neglected and forgotten cationic, air-stable, 18-valence electron, heteroleptic sandwich complex (cycloheptatrienyl)(cyclopentadienyl)manganese, which was reported independently by Fischer and by Pauson about 50 years ago. Using advanced high-power LED photochemical synthesis, an expedient rapid access to the parent complex and to functionalized derivatives with alkyl, carboxymethyl, bromo, and amino substituents was developed. A thorough study of these "tromancenium" salts by a range of spectroscopic techniques (H/C/Mn-NMR, IR, UV-vis, HRMS, XRD, XPS, EPR), cyclic voltammetry (CV), and quantum chemical calculations (DFT) shows that these manganese sandwich complexes are unique metallocenes with quite different chemical and physical properties in comparison to those of isoelectronic cobaltocenium salts or (cycloheptatrienyl)(cyclopentadienyl) sandwich complexes of the early transition metals. Read More

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Autotandem Catalysis: Inexpensive and Green Access to Functionalized Ketones by Intermolecular Iron-Catalyzed Amidoalkynylation/Hydration Cascade Reaction via N-Acyliminium Ion Chemistry.

Chemistry 2021 Aug 3. Epub 2021 Aug 3.

Universite du Havre, URCOM, 25, Rue Philippe Lebon, BP 540, 76058, Le Havre, FRANCE.

Iron-based catalysts were applied in cascade-type reactions for the synthesis of different carbonyl compounds. The reactions proceeded by a new iron-catalyzed cascade of alkynylation/hydration by using both the σ- and π-Lewis acid properties of iron salts. The alkynylation reactions of several endo and exocyclic acetoxylactams were achieved with three different catalysts including FeCl 3 . Read More

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Mild Intermolecular Synthesis of a Cyclopropane-Containing Tricyclic Skeleton: Unusual Reactivity of Isobenzopyryliums.

Angew Chem Int Ed Engl 2021 09 31;60(39):21272-21276. Epub 2021 Aug 31.

Jiangsu Key Laboratory of Advanced Catalytic Materials & Technology, School of Petrochemical Engineering, Changzhou University, Changzhou, China.

Cyclopropanes embedded in a polycyclic bridged architecture are a versatile structural motif, but such complex frameworks often impose substantial synthetic challenges. Herein we introduce a new approach for the expedient access to such spring-loaded strained systems via an exceptionally mild intermolecular convergent process between the readily available isobenzopyryliums and vinyl boronic acids. Different from the typical conventional approaches, our protocol does not involve the highly active carbenoid intermediates or strong conditions in order to overcome the disfavored kinetic and thermodynamic problems. Read More

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September 2021

CpTiCl-Mediated Reductive Cyclization: Total Synthesis of Pestalotiolactone A, Myrotheciumone A, and Scabrol A.

J Org Chem 2021 Sep 1;86(17):11812-11821. Epub 2021 Aug 1.

Department of Organic Chemistry, Indian Institute of Science, Bengaluru 560012, India.

The first stereoselective total syntheses of fungal secondary metabolites monoterpenoid (+)-pestalotiolactone A, meroterpenoid (-)-myrotheciumone A, and iridoid lactone (+)-scabrol A have been accomplished in an expedient unified approach starting from d-(+)-malic acid employing an epoxide opening-radical cyclization protocol initiated by CpTi(III)Cl as a key step to assemble the core bicyclic lactone moieties of these molecules with complete diastereoselective control. Finally, the deoxygenation and methylation delivered the target natural products. Read More

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September 2021

One-Step Synthesis of Photoaffinity Probes for Live-Cell MS-Based Proteomics.

Chemistry 2021 Jul 30. Epub 2021 Jul 30.

GlaxoSmithKline R&D, Gunnels Wood Road, Stevenage, SG1 2NY, UK.

We present a one-step Ugi reaction protocol for the expedient synthesis of photoaffinity probes for live-cell MS-based proteomics. The reaction couples an amine affinity function with commonly used photoreactive groups, and a variety of handle functionalities. Using this technology, a series of pan-BET (BET: bromodomain and extra-terminal domain) selective bromodomain photoaffinity probes were obtained by parallel synthesis. Read More

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An expedient route to tricyanovinylindoles and indolylmaleimides from o-alkynylanilines utilising DMSO as a one-carbon synthon.

Org Biomol Chem 2021 Aug 27;19(31):6847-6857. Epub 2021 Jul 27.

Department of Chemistry, Indian Institute of Technology Guwahati, 781039, Assam, India.

A Pd(ii)/Cu(ii) catalysed domino synthesis of tricyanovinylindoles has been achieved using DMSO as a one-carbon synthon. The reaction proceeds via the construction of 2-aryl-3-formyl indole followed by sequential addition of malononitrile and a CN resulting in two C-C, one C[double bond, length as m-dash]C and one C-N bonds in the final product. Furthermore, post-synthetic modification results in the unprecedented formation of 4-cyano-3-indolylmaleimides. Read More

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Sequential C-H activation enabled expedient delivery of polyfunctional arenes.

Chem Commun (Camb) 2021 Aug;57(65):8075-8078

School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, China.

Modular construction of polyfunctional arenes from abundant feedstocks stands as an unremitting pursue in synthetic chemistry, accelerating the discovery of drugs and materials. Herein, using the multiple C-H activation strategy with versatile imidate esters, the expedient delivery of molecular libraries of densely functionalized sulfur-containing arenes was achieved, which enabled the concise construction of biologically active molecules, such as Bipenamol. Read More

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Engineering analysis of multienzyme cascade reactions for 3'-sialyllactose synthesis.

Biotechnol Bioeng 2021 Jul 21. Epub 2021 Jul 21.

Austrian Centre of Industrial Biotechnology, Graz, Austria.

Sialo-oligosaccharides are important products of emerging biotechnology for complex carbohydrates as nutritional ingredients. Cascade bio-catalysis is central to the development of sialo-oligosaccharide production systems, based on isolated enzymes or whole cells. Multienzyme transformations have been established for sialo-oligosaccharide synthesis from expedient substrates, but systematic engineering analysis for the optimization of such transformations is lacking. Read More

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Solvent-Dependent Cyclization of 2-Alkynylanilines and ClCFCOONa for the Divergent Assembly of -(Quinolin-2-yl)amides and Quinolin-2(1)-ones.

Org Lett 2021 Aug 14;23(15):5599-5604. Epub 2021 Jul 14.

Institute of Next Generation Matter Transformation, College of Materials Science & Engineering, Huaqiao University, 668 Jimei Boulevard, Xiamen, Fujian 361021, People's Republic of China.

Herein, we present an expedient Cu-catalyzed [5 + 1] cyclization of 2-alkynylanilines and ClCFCOONa to divergent construction of -(quinolin-2-yl)amides and quinolin-2(1)-ones by regulating the reaction solvents. Notably, nitrile acts as a solvent and performs the Ritter reactions. ClCFCOONa is used as a C1 synthon in this transformation, which also represents the first example for utilization of ClCFCOONa as an efficient desiliconization reagent. Read More

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Synthesis of Cardiotonic Steroids Oleandrigenin and Rhodexin B.

J Org Chem 2021 Aug 13;86(15):10249-10262. Epub 2021 Jul 13.

Chemistry Department, University of Michigan, 930 N. University Avenue, Ann Arbor, Michigan 48109, United States.

This article describes a concise synthesis of cardiotonic steroids oleandrigenin () and its subsequent elaboration into the natural product rhodexin B () from the readily available intermediate () that could be derived from the commercially available steroids testosterone or DHEA three-step sequences. These studies feature an expedient installation of the β16-oxidation based on β14-hydroxyl-directed epoxidation and subsequent epoxide rearrangement. The following singlet oxygen oxidation of the C17 furan moiety provides access to oleandrigenin () in 12 steps (LLS) and a 3. Read More

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Diastereoselective, Multicomponent Synthesis of Pyrrolopyrazinoquinazolinones via a Tandem Quinazolinone Rearrangement/Intramolecular Ring Closure of Tautomeric ()-Benzamidines.

Org Lett 2021 Aug 12;23(15):5799-5803. Epub 2021 Jul 12.

Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, Wisconsin 53706, United States.

An expedient route to enantiopure, diastereomeric pyrrolopyrazinoquinazolinones was developed following the discovery of a domino quinazolinone rearrangement-intramolecular cyclization of N-H benzamidines. A Ugi-Mumm-Staudinger sequence employing an optically pure proline derivative gave quinazolinones that, upon -Boc deprotection, rearranged to tautomeric -benzamidines. Subsequent spontaneous cyclization afforded 15 diastereomeric pyrazinoquinazolinone pairs in up to 83% overall yield and 89:11 d. Read More

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Cascade intramolecular Prins/Friedel-Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5-benzo[7]annulen-7-ols.

Beilstein J Org Chem 2021 22;17:1481-1489. Epub 2021 Jun 22.

Department of Chemistry, Fudan University, 2005 Songhu Road, Shanghai 200438, P. R. China.

The treatment of 2-(2-vinylphenyl)acetaldehydes or 3-(2-vinylphenyl)propanals with BF·EtO 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-5-benzo[7]annulen-7-ol derivatives. Read More

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Selective C-F Bond Allylation of Trifluoromethylalkenes.

Angew Chem Int Ed Engl 2021 Sep 28;60(37):20237-20242. Epub 2021 Jul 28.

Technical Institute of Fluorochemistry (TIF), Institute of Advanced Synthesis (IAS), School of Chemistry and Molecular Engineering, Nanjing Tech University, 30 South Puzhu Road, Nanjing, 211816, P. R. China.

Selective C-F bond functionalization of CF group represents an appealing strategy for the incorporation of pharmaceutically privileged difluoromethylene moiety. Despite the recent significant advancement attained in the functionalization of Ar-CF molecules, prescriptions amenable for alkenyl-CF congeners remain sufficiently inadequate. Herein, we report a strategically novel protocol for the C-F bond elaboration of trifluoromethylalkene derivatives. Read More

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September 2021

An improved method for the incorporation of fluoromethyl ketones into solid phase peptide synthesis techniques.

RSC Adv 2021 Jun 8;11(33):20457-20464. Epub 2021 Jun 8.

Peptide Chemistry STP, The Francis Crick Institute 1 Midland Road London NW1 1AT UK +44 (0)203 796 2359.

An improved and expedient technique for the synthesis of peptidyl-fluoromethyl ketones is described. The methodology is based on prior coupling of an aspartate fluoromethyl ketone to a linker and mounting it onto resin-bound methylbenzhydrylamine hydrochloride. Subsequently, by utilising standard Fmoc peptide procedures, a number of short Z-protected peptides were synthesised and assessed as possible inhibitors of the main protease from SARS-CoV-2 (3CL). Read More

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Transition-Metal-Catalyzed Directing Group Assisted (Hetero)aryl C-H Functionalization: Construction of C-C/C-Heteroatom Bonds.

Chem Rec 2021 Jun 23. Epub 2021 Jun 23.

Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati, 781039.

Transition-metal-catalyzed C-H functionalization is one of the fascinating scientific fronts in organic synthesis for the formation of conjugated arenes and has emerged as a benchmark to revolutionize the synthetic enterprise since past decades. In this realm, chelation-guided functionalization of C-H bonds using an exogenous directing group has received considerable attention recently for the expedient regioselective construction of C-C and C-heteroatom bonds as an efficient and sustainable alternative. This article outlines our contribution towards a wide variety of transformations that have been achieved by the directed C-H functionalization through the fine tuning of catalytic systems. Read More

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Revisiting ageless antiques; synthesis, biological evaluation, docking simulation and mechanistic insights of 1,4-Dihydropyridines as anticancer agents.

Bioorg Chem 2021 Sep 4;114:105054. Epub 2021 Jun 4.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Tanta University, Postal code: 31527, Tanta, Egypt.

The historic DHP nucleus was serendipitously discovered by Arthur Hantzsch about 130 years ago and is still considered a hidden treasure for various pharmacological activities. Twenty-one DHP analogues were synthesized using the expedient one pot Hantzsch synthesis for screening as anticancer agents. Initially, the in vitro anti-proliferative single dose against a panel of 18 cancer cell lines showed that compounds 11b and 8f were the superlative candidates regarding their antitumor effect (GI% mean = 66. Read More

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September 2021

Expedient Synthesis of Bridged Bicyclic Nitrogen Scaffolds via Orthogonal Tandem Catalysis.

Angew Chem Int Ed Engl 2021 09 11;60(40):21988-21996. Epub 2021 Aug 11.

Organic Synthesis Division, Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, 2020, Antwerp, Belgium.

Bridged nitrogen bicyclic skeletons have been accessed via unprecedented site- and diastereoselective orthogonal tandem catalysis from readily accessible reactants in a step economic manner. Directed Pd-catalyzed γ-C(sp )-H olefination of aminocyclohexane with gem-dibromoalkenes, followed by a consecutive intramolecular Cu-catalyzed amidation of the 1-bromo-1-alkenylated product delivers the interesting normorphan skeleton. The tandem protocol can be applied on substituted aminocyclohexanes and aminoheterocycles, easily providing access to the corresponding substituted, aza- and oxa-analogues. Read More

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September 2021

Total synthesis of crotophorbolone.

Chem Sci 2020 Jun 19;11(27):7177-7181. Epub 2020 Jun 19.

Key Laboratory of Green Chemistry & Technology of Ministry of Education, College of Chemistry, Sichuan University 29 Wangjiang Rd. Chengdu Sichuan 610064 China

As a natural diterpenoid, crotophorbolone possesses a challenging ,-5/7/6 framework decorated with six contiguous stereogenic centers and is structurally and biogenetically related to tigliane-type diterpenoids with intriguing bioactivities such as phorbol and prostratin. Based on the convergent strategy, we completed an eighteen-step total synthesis of crotophorbolone starting from (-)-carvone and (+)-dimethyl-2,3--isopropylidene-l-tartrate. The key elements of the synthesis involve expedient installation of the six-membered ring and the five-membered ring with multiple functional groups at an early stage, cyclization of the seven-membered ring through alkenylation of the ketone between the five-membered ring and the six-membered ring, functional group-sensitive ring-closing metathesis and final selective introduction of hydroxyls at C and C. Read More

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Modular Synthesis of a Versatile Double-Allylation Reagent for Complex Diol Synthesis.

Angew Chem Int Ed Engl 2021 07 11;60(29):16027-16034. Epub 2021 Jun 11.

Department of Chemistry, Indiana University, 800 E. Kirkwood Ave., Bloomington, IN, 47401, USA.

Double-allylation reagents allow for the construction of highly complex molecules in an expedient fashion. We have developed an efficient, modular, and enantioselective approach towards accessing novel variants of these reagents through Cu/Pd-catalyzed alkenylboration of alkenylboron derivatives. Importantly, we demonstrate novel use of an allylBdan reagent directly in a stereocontrolled allylation without initial deprotection to the boronic ester. Read More

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Perimeter Coordinated Diastereomeric Rh(I) Complex of Helically Twisted Weakly Aromatic Hybrid Singly N-Confused β-β Fused Ferrocenoporphyrinoids.

J Org Chem 2021 Jun 7;86(12):8015-8026. Epub 2021 Jun 7.

School of Chemical Sciences, Indian Association for the Cultivation of Science, 2A/2B Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, India.

Expedient synthesis, spectroscopic, solid state structural proof, and theoretical study of helically twisted weakly aromatic hybrid singly N-confused ferrocenoporphyrinoids and the peripheral coordinated Rh(I) complex are reported. The X-ray crystal structure of the macrocycles reveals an ambiguously inverted pyrrole ring reinforcing regioselective β,β-linkage with the spatially adjacent N-confused -methyl pyrrole ring leading to endocyclic extension of macrocyclic π-conjugation via tricyclic [5.5. Read More

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Total synthesis of biseokeaniamides A-C and late-stage electrochemically-enabled peptide analogue synthesis.

Chem Sci 2020 Jul 30;11(39):10752-10758. Epub 2020 Jul 30.

Research School of Chemistry, Australian National University Canberra ACT 2601 Australia

The first total synthesis of cytotoxic cyanobacterial peptide natural products biseokeaniamides A-C is reported employing a robust solid-phase approach to peptide backbone construction followed by coupling of a key thiazole building block. To rapidly access natural product analogues, we have optimized an operationally simple electrochemical oxidative decarboxylation-nucleophilic addition pathway which exploits the reactivity of native C-terminal peptide carboxylates and abrogates the need for building block syntheses. Electrochemically-generated ,-acetal intermediates are engaged with electron-rich aromatics and organometallic reagents to forge modified amino acids and peptides. Read More

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A general prodrug nanohydrogel platform for reduction-triggered drug activation and treatment of taxane-resistant malignancies.

Acta Biomater 2021 08 1;130:409-422. Epub 2021 Jun 1.

The First Affiliated Hospital, School of Medicine, Zhejiang University; NHC Key Laboratory of Combined Multi-Organ Transplantation, Key Laboratory of Organ Transplantation, Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Zhejiang Province, Hangzhou 310003, PR China. Electronic address:

Chemotherapy has been widely used for treating the vast majority of cancer patients. Unfortunately, only a fraction of patients can respond to chemotherapies, but these patients still experience severe side effects. In this context, a wide range of nanotherapeutic platforms have been developed with the aim of improving treatment outcomes while reducing drug toxicities. Read More

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A Transient Directing Group Strategy Enables Enantioselective Multicomponent Organofluorine Synthesis.

J Am Chem Soc 2021 Jun 2;143(24):8962-8969. Epub 2021 Jun 2.

Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.

The vicinal fluorofunctionalization of alkenes represents an expedient strategy for converting feedstock olefins into valuable fluorinated molecules and as such has garnered significant attention from the synthetic community; however, current methods remain limited in terms of scope and selectivity. Here we report the site-selective palladium-catalyzed three-component coupling of alkenylbenzaldehydes, arylboronic acids, and -fluoro-2,4,6-trimethylpyridinium hexafluorophosphate facilitated by a transient directing group. The synthetically enabling methodology constructs vicinal stereocenters with excellent regio-, diastereo-, and enantioselectivities, forging products that map onto bioactive compounds. Read More

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Chemical Synthesis of Activity-Based E2-Ubiquitin Probes for the Structural Analysis of E3 Ligase-Catalyzed Transthiolation.

Angew Chem Int Ed Engl 2021 07 22;60(31):17171-17177. Epub 2021 Jun 22.

Tsinghua-Peking Center for Life Sciences, Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Center for Synthetic and Systems Biology, Department of Chemistry, Tsinghua University, Beijing, 100084, China.

Activity-based E2 conjugating enzyme (E2)-ubiquitin (Ub) probes have recently emerged as effective tools for studying the molecular mechanism of E3 ligase (E3)-catalyzed ubiquitination. However, the preparation of existing activity-based E2-Ub probes depends on recombination technology and bioconjugation chemistry, limiting their structural diversity. Herein we describe an expedient total chemical synthesis of an E2 enzyme variant through a hydrazide-based native chemical ligation, which enabled the construction of a structurally new activity-based E2-Ub probe to covalently capture the catalytic site of Cys-dependent E3s. Read More

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