Article
Chemistry, Organic
Julia O. Strelnikova, Alexander N. Koronatov, Nikolai Rostovskii, Alexander F. Khlebnikov, Olesya Khoroshilova, Mariya A. Kryukova, Mikhail S. Novikov
Summary: The domino reaction catalyzed by Rh-2(Piv)(4) leads to the formation of N-sulfonylated (Z)-2-(2-aminovinyl)imidazoles, providing a direct and flexible access to the desired compounds.
Article
Chemistry, Organic
Yi-Min Fan, Josemon George, Jiao Yu J. Wang, Michael G. Gardiner, Michelle L. Coote, Michael S. Sherburn
Summary: Through the study, it was found that imines can participate in intermolecular formal [4 + 2] cycloadditions with dendralenes, forming hexahydro- and octahydro-isoquinoline structures. After optimizing the conditions, the formal aza-Diels-Alder reaction proceeds with high regio- and stereoselectivity.
Article
Chemistry, Organic
Rafael G. Uceda, Esther Roldan-Molina, Jorge A. R. Navarro, J. Enrique Oltra
Summary: This study explores the use of electron-deficient dienes as substrates in the aza Diels-Alder reaction, showing that the amide group significantly influences the yield of the reaction products.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Stephen M. Bierschenk, Judy Y. Pan, Nicholas S. Settineri, Ulrike Warzok, Robert G. Bergman, Kenneth N. Raymond, F. Dean Toste
Summary: A highly enantioselective aza-Darzens reaction catalyzed by an enantiopure supramolecular host has been discovered. Changes in enantioselectivity were observed by substituting the external chiral amide in the catalysts, and these changes were correlated to the flexibility of the supramolecular host scaffold as measured by guest exchange kinetics. By substituting the gallium(III)based host with one based on indium(III), the most flexible and selective catalyst was developed.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Organic
Shuheng Xu, Linwei Zeng, Sunliang Cui
Summary: The Diels-Alder (DA) reaction and hetero-Diels-Alder (HDA) reaction are powerful methods for constructing carbocycles and heterocycles. This study presents an integrated building block that combines both DA and HDA reactions, utilizing triazenyl dienes to undergo the DA reaction and the newly released alkene moiety and triazene to engage in the HDA reaction.
Article
Chemistry, Organic
Elisa Brambilla, Sara Leoni, Giorgio Abbiati, Valentina Pirovano, Elisabetta Rossi
Summary: Spiroindolenines were used as cyclic imine substrates in formal aza-Diels-Alder reactions with Danishefsky's diene or silyloxy-substituted electron-rich dienes, leading to the synthesis of tetrahydropyrido[1,2-a]spiroindolinones under mild conditions in the presence of ytterbium triflate as a Lewis acidic catalyst, with good yields. The reaction results in the preparation of a small library of a new class of conformational constrained heterocyclic derivatives that easily undergo selective and efficient manipulations.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Physical
Victor Laina-Martin, Jorge Humbrias-Martin, Ruben Mas-Balleste, Jose A. Fernandez-Salas, Jose Aleman
Summary: A highly efficient enantioselective inverse-electron-demand aza-Diels-Alder reaction has been developed, allowing the synthesis of benzofuran-fused 2-piperidinol derivatives with three contiguous stereocenters in a highly selective manner. Density functional theory calculations support the reaction mechanism and reveal the mode of action of the hydrogen-bond donor.
Article
Chemistry, Multidisciplinary
Qun Zhao, Yao Li, Qing-Xia Zhang, Jin-Pei Cheng, Xin Li
Summary: The highly enantioselective aza-Diels-Alder reaction of 2-aryl-3H-indol-3-ones with unactivated dienes using a B(C6F5)(3)/chiral phosphoric acid catalyst system under mild conditions offers rapid access to a broad scope of tetrahydropyridine derivatives with excellent outcomes. The reaction is efficient, with maintained enantioselectivity even at lower catalyst loadings of 0.1 mol %. DFT calculations provide convincing evidence for the interpretation of stereoselection.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Guanghao Huang, Cyrille Kouklovsky, Aurelien de la Torre
Summary: The first enantioselective total synthesis of (+)-lucidumone is described, involving key steps such as an enantioselective inverse-electron-demand Diels-Alder cycloaddition and C-O bond formation. The synthesis is scalable and produced over one gram of natural product in one batch.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Organic
Aurapat Ngamnithiporn, Padon Chuentragool, Poonsakdi Ploypradith, Somsak Ruchirawat
Summary: This article reports the development of a novel three-component aza-Diels-Alder reaction, employing sultines, aldehydes, and amines as substrates. By using Cu(OTf)(2) as a Lewis acid catalyst and the in situ generation of imines, a wide range of polysubstituted tetrahydro-isoquinoline derivatives can be easily prepared from readily available precursors. The synthetic utility of these products is demonstrated through various product transformations, including the synthesis of tricyclic N-heterocycles.
ASIAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Wei-Ling Jiang, Bin Huang, Meng-Xiang Wu, Ye-Kai Zhu, Xiao-Li Zhao, Xueliang Shi, Hai-Bo Yang
Summary: The preparation of stable MOFs with organic radicals is challenging due to the reactivity of most organic radicals. A novel MOF containing phenazine radical cations was successfully synthesized using a post-synthetic modification strategy. The resulting MOF demonstrated high catalytic activity in aza-Diels-Alder reactions and excellent stability and recyclability, suggesting the potential of the developed strategy for preparing radical-based MOFs for heterogeneous catalysis in organic synthesis.
CHEMISTRY-AN ASIAN JOURNAL
(2021)
Article
Chemistry, Organic
Pengfei Jia, Zhiqian Lin, Shenmeng Yan, Jiao Liang, Cankun Luo, Ruizhi Lai, Li Hai, Zhongzhen Yang, Yong Wu
Summary: This study reports a new synthetic method for the one-step synthesis of Oxo-bridged dibenzoazocines via ruthenium-catalyzed [4 + 3]-cycloannulation of aza-ortho-quinone methides with carbonyl ylides at room temperature. The method exhibits exclusive diastereoselectivity, excellent yield, mild reaction conditions, and broad substrate scope. The product can be prepared on a gram scale and further functionalized into diverse substituted dihydroisobenzofuran derivatives and a dibenzoazocine scaffold.
Article
Chemistry, Organic
Ryota Mori, Minenari Asakura, Yukinori Kobayashi, Hiromu Mashimo, Makoto Roppongi, Satoshi Ito
Summary: In this study, we report the synthesis and absorption properties of pi-conjugated asymmetric aza-BODIPYs by nitrosation and retro-Diels-Alder reaction, as well as the first-time synthesis of aza-BODIPY fused with [2.3]naphtho and [2.3]anthra structures, and pi-conjugated aza-O-chelate BODIPY using this method.
TETRAHEDRON LETTERS
(2022)
Article
Chemistry, Organic
Li Pang, Shu-Jun Fang, Pei-Sen Zou, Wang Wang, Jun-Cheng Su, Xiao-Qing Liu, Cheng-Xue Pan, Dong-Liang Mo, Gui-Fa Su
Summary: We report a transition-metal free [4 + 4] cycloaddition reaction between 2-alkynyl quinazolines and aza-ortho-quinone methides (ao-QMs) generated from 2-(bromomethyl)anilines, leading to the synthesis of various [1,5]diazocino[2,1-b]quinazolinones in good to excellent yields under mild reaction conditions and short reaction time. Furthermore, a [1,5]diazocino[2,1-b]quinazolinone derived from estrone was easily prepared in 30% total yield over five steps, and showed significant inhibition of nitric oxide generation in LPS-stimulated RAW264.7 cells. This method offers advantages such as broad substrate scope, gram-scale preparation, and simple purification operation without flash column chromatography.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Multidisciplinary
Masao Ohashi, Dan Tan, Jiayan Lu, Cooper S. Jamieson, Daiki Kanayama, Jiahai Zhou, K. N. Houk, Yi Tang
Summary: The synthesis of cis-decalin structures using [4 + 2] cycloaddition with high stereoselectivity is challenging. In this study, we investigated the biosynthetic pathway of the fungal natural product fischerin (1) and identified a novel pericyclase, FinI, which catalyzes this reaction. The cocrystal structure of FinI, a predicted O-methyltransferase, with the product and SAM provides valuable insights into the natural formation of cis-decalin.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Organic
Yousra Hamdane, Pradeep S. Chauhan, Suresh Vutla, Mukandila Mulumba, Huy Ong, William D. Lubell
Summary: Fifteen N-aminoimidazolone (Nai) dipeptides with different 5-position side-chain groups were synthesized through regioselective proline-catalyzed reactions and acid-mediated dehydration. Introducing 5-aryl-Nai dipeptides into CD36 receptor peptide ligands provided insights into the conformation responsible for binding affinity and anti-inflammatory activity.
Article
Cell Biology
Marie-France Dorion, Mukandila Mulumba, Shuya Kasai, Ken Itoh, William D. Lubell, Huy Ong
Summary: This study reveals that the CD36 ligand MPE-001 protects RPE cells from oxidative stress by promoting autophagy. MPE-001 reduced oxidative stress and cell apoptosis induced by NaIO3, restored autophagic flux, and this protective effect was associated with an increase in mature autophagosomes.
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
(2021)
Article
Chemistry, Multidisciplinary
Xingjuan Zhao, Shirley Campbell, Patrick Z. El-Khoury, Yuechen Jia, Gregory Q. Wallace, Audrey Claing, C. Geraldine Bazuin, Jean-Francois Masson
Summary: In this study, surface-enhanced Raman scattering (SERS)-active nanofibers covered with 4-mercaptopyridine (4-Mpy)-modified gold nanoparticles were constructed to detect Hg2+ and Ag+. The relative intensity of characteristic Raman peaks was used to quantify metal ion concentration, greatly increasing reproducibility. The nanosensors demonstrated good sensitivity, high reproducibility, and excellent selectivity, allowing for detection of metal ions at subcellular levels.
Article
Chemistry, Medicinal
Ragnhild G. Ohm, Mukandila Mulumba, Ramesh M. Chingle, Ahsanullah, Jinqiang Zhang, Sylvain Chemtob, Huy Ong, William D. Lubell
Summary: Expanding cyclic peptide diversity through A(3)-macrocyclization and introducing new components has shown the importance of triple bonds and residues like N-epsilon-allyl lysine in high CD36 binding affinity, aiding in the development of ideal CD36 modulators to curb macrophage-driven inflammation.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Anh Minh Thao Nguyen, Skye Brettell, Noelie Douanne, Claudia Duquette, Audrey Corbeil, Emanuella F. Fajardo, Martin Olivier, Christopher Fernandez-Prada, William D. Lubell
Summary: The study demonstrated that derivatives with a single methyl group in N-methylated lipopeptides exhibit higher activity against various strains of leishmaniasis protozoan and have relatively high potency against resistant strains. Additionally, the systematic study of the effects of methylation and turn geometry on anti-parasitic activity revealed the importance of an extended conformer about the central residues and conformational mobility by tertiary amide isomerization and turn geometry at the extremities of the active peptides.
Article
Chemistry, Organic
Ramakotaiah Mulamreddy, Xin Hou, Sylvain Chemtob, William D. Lubell
Summary: The synthesis of 6-hydroxymethyl indolizidin-2-one amino acids from L-serine involves 10 steps, including intramolecular ring opening and lactam formation. X-ray analyses showed ideal peptide geometry, and the analogue exhibited inhibitory activity on myometrial contractility within a prostaglandin-F-2 alpha receptor modulator.
Article
Multidisciplinary Sciences
Jenna Giubilaro, Doris A. Schuetz, Tomasz M. Stepniewski, Yoon Namkung, Etienne Khoury, Monica Lara-Marquez, Shirley Campbell, Alexandre Beautrait, Sylvain Armando, Olivier Radresa, Jean Duchaine, Nathalie Lamarche-Vane, Audrey Claing, Jana Selent, Michel Bouvier, Anne Marinier, Stephane A. Laporte
Summary: A novel dual Ras and ARF6 inhibitor named Rasarfin was identified in a high-throughput screen for receptor trafficking inhibitors. Rasarfin blocks agonist-mediated internalization of GPCRs, inhibits ERK1/2 signaling, MAPK and Akt signaling, and prevents cancer cell proliferation. The unique binding modality of Rasarfin within the SOS-binding domain of Ras was revealed through in silico modeling and in vitro studies, indicating its potential for inhibiting oncogenic cellular responses.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Ramakotaiah Mulamreddy, William D. Lubell
Summary: This paper reports the synthesis of 5- and 7-hydroxy indolizidin-2-one N-(Boc)amino acids from L-serine, and discusses their potential in peptide mimicry.
Article
Multidisciplinary Sciences
Emilie Fiola-Masson, Julie Artigalas, Shirley Campbell, Audrey Claing
Summary: A study found that PDGF and Ang II can activate the GTPase ARF6 to regulate invasive capacities of vascular smooth muscle cells. PDGF activates ARF6 through the MAPK/ERK1/2, PI3K/AKT and PAK pathways, while Ang II only activates ARF6 through the MAPK/ERK1/2 and PAK pathways. Activation of ARF6 leads to activation of MMP14 and decreased release of MMP2.
SCIENTIFIC REPORTS
(2022)
Editorial Material
Biochemistry & Molecular Biology
William D. Lubell
Article
Biochemistry & Molecular Biology
Ramesh M. Chingle, Masahiko Imai, Sarah Altman, Daisuke Saito, Noriko Takahashi, Terrence R. Burke
Summary: Retinoic acid binds to retinoic acid receptors to regulate gene expression and has important functions such as cell proliferation and differentiation. A new p-dodecylaminophenol derivative, without side effects or toxicity and effective against a wide range of cancers, has been developed. Introducing the carboxylic acid motif found in retinoids potentially enhances the anti-proliferative effects.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Xiaozheng Wei, Sitan Diarra, Antoine Douchez, Juliana C. Cunico Dallagnol, Terence E. Hebert, David Chatenet, William D. Lubell
Summary: The study of Urotensin II receptor (UT) modulators can help us understand the roles of the endogenous cyclic peptide ligands urotensin II (UII) and urotensin II-related peptide (URP) in disease etiology. By designing and synthesizing a series of compounds, selective modulators of hUII and URP activities were discovered, which can affect biological processes such as vasoconstriction.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Anh Minh Thao Nguyen, Moran Shalev-Benami, Chloe Rosa-Teijeiro, Ana Victoria Ibarra-Meneses, Ada Yonath, Anat Bashan, Charles L. Jaffe, Martin Olivier, Christopher Fernandez-Prada, William D. Lubell
Summary: A strategy for preparing potent anisomycin derivatives with reduced host toxicity has been revealed by assessing structure-activity relationships for anti-protozoan activity. Different modifications of the alcohol, amine, and aromatic functional groups have been studied, and it was found that introducing substituents at the para-phenol moiety of anisomycin can maintain the anti-protozoan potency without significant loss of activity against the host.
Article
Chemistry, Organic
Zhihong Luo, Lei Xu, Xiaomin Tang, Xuejun Zhao, Tong He, William D. Lubell, Jinqiang Zhang
Summary: In this study, novel all-hydrocarbon cross-linked aza-stapled peptides were designed and synthesized for the first time. These peptides exhibited increased anti-tumor activity, binding affinities, and cell membrane permeability compared to their linear counterparts.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Chemistry, Organic
David Hymel, Kohei Tsuji, Robert A. Grant, Ramesh M. Chingle, Dominique L. Kunciw, Michael B. Yaffe, Terrence R. Burke
Summary: This study focuses on the design and synthesis of macrocyclic peptide mimetics targeting the Plk1 PBD, utilizing a new glutamic acid analog to enhance affinity and access hidden cryptic pockets. The introduction of this new amino acid analog enables additional hydrogen-bonding interactions and the first example of high affinity ligands accessing the cryptic pocket without relying on histidine residues. These concepts may be beneficial for further research on Plk1 PBD and other PPI targets.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
