Article
Chemistry, Multidisciplinary
Caroline Dorsch, Christoph Schneider
Summary: We describe a catalytic asymmetric cyclization of 1-aryl terpenols to produce enantiomerically enriched Delta(9)-cis-tetrahydrocannabinoid scaffolds in a one-step process. Powerful chiral catalysts, strongly acidic imidodiphosphorimidates (IDPis), were identified to give the products in good yields and excellent enantioselectivity. After MOM-deprotection, some naturally occurring cannabimimetics such as (-)-cis-Delta(9)-tetrahydrocannabinol and (-)-perrottetinene, as well as some unnatural analogues, were accessible through a simple 3-step biomimetic sequence.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Qi-Wei Lang, Xiang -Yang Qian, Xiu-Lin He, Hui Geng, Jian-Feng Zheng, Pei-Qiang Huang
Summary: A flexible asymmetric approach for the synthesis of 2,5-disubstituted cis-decahydroquinolines (DHQs) ring system from glutaraldehyde and methyl (E)-5-nitropent-4-enoate is reported. The enantioselective organocatalytic domino Michael/Henry reaction, subsequent one-pot, four-step transformation, and one-pot amide reductive alkylation method are the key steps responsible for the stereoselective syntheses of the target compounds.
Article
Chemistry, Applied
Achille Antenucci, Giovanni Ghigo, Davide Cassetta, Marco Alcibiade, Stefano Dughera
Summary: Chiral phosphoric acids (CPAs) and their salts have been widely used as privileged catalysts in asymmetric transformations. Previous efficient CPAs have relied on C-2 symmetry and axial chirality, with the only exception being TADDOL derivatives. In this study, we have designed and synthesized C-2 symmetric cycloglycerophosphates (cGPAs), which were applied in the addition of trimethylsilyl cyanide (TMSCN) to aldehydes and ketones. The corresponding cyanohydrins were obtained with yields between 77% and 99% and enantiomeric excesses between 84.2% and 99.5%, in 27 examples. A DFT computational model was also used to rationalize the reaction mechanism and stereochemical outcome.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Review
Chemistry, Medicinal
Everton M. da Silva, Herika D. A. Vidal, Arlene G. Correa
Summary: Researchers are constantly looking for new compounds with antiviral activity and facing challenges in synthesizing these compounds, especially those with stereogenic centers. Organocatalytic methods play a crucial role in improving synthetic route efficiency and sustainability for important commercially antiviral chiral drugs.
Article
Chemistry, Multidisciplinary
Fei Li, Jing-Lan Kan, Bing-Jian Yao, Yu-Bin Dong
Summary: A general and efficient organocatalytic asymmetric polymerization approach has been developed for the synthesis of chiral covalent organic frameworks (CCOFs). Using a chiral 2-methylpyrrolidine catalyst, a series of chiral beta-ketoenamine-CCOFs were directly constructed from prochiral aldehyde- and primary amine-monomers. The obtained CCOFs can be further metalated and used as highly efficient catalysts.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Organic
Ying Zhou, Yan Zhang, Canghai Yu, Xin Yue, Feng Jiang, Wengang Guo
Summary: This study discovered a method that utilizes high energy intermediates to construct valuable chiral products. By catalytic asymmetric protonation of in situ generated ammonium ylide using chiral Bronsted acid under visible-light irradiation, the desired α-amino esters were obtained with moderate to high enantioselectivity and yield. This method not only demonstrates the compatibility of chiral phosphoric acid catalysis with free carbene insertion reactions, but also indicates the significance of arylamine's pKa value in tuning the enantioselectivity of the reaction.
TETRAHEDRON LETTERS
(2023)
Article
Chemistry, Organic
Feng Jiang, Tengfei Meng, Ying Zhou, Zhenying Xiong, Yupei Zhao, Wengang Guo
Summary: We report an enantio- and diastereodivergent synthesis of enantioenriched fluorenes with broad substrate scope and high enantioselectivity (up to 99% ee) under low catalyst loading (0.1 mol %). The success of this method lies in the pseudo-diastereodivergent desymmetrization of stereoisomers of meso-epoxides enabled by the same organocatalyst. Furthermore, some of the chiral fluorenes obtained exhibit high fluorescence quantum yields (up to 76.6%), as evidenced by photophysical properties studies.
Article
Chemistry, Multidisciplinary
Remi Andres, Fenggang Sun, Qian Wang, Jieping Zhu
Summary: An asymmetric Pictet-Spengler reaction of alpha-ketoesters was developed, achieving high yields and ee values. The reaction mechanism was proposed to involve deprotonation of the pentahydro-beta-carbolinium ion as the rate- and enantioselectivity-determining step. This methodology was successfully applied in the enantioselective total synthesis of (+)-alstratine A, and the remeasurement of its [a](D) value revealed a correction in the initial report.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Alberto Marban-Gonzalez, Gaspar Maravilla-Moreno, Josue Vazquez-Chavez, Marcos Hernandez-Rodriguez, Rodrigo Said Razo-Hernandez, Mario Ordonez, Jose Luis Viveros-Ceballos
Summary: A versatile intermediate for further stereocontrolled transformations to access enantiopure cis-fused octahydroisoindolones was synthesized through kinetically controlled cyclocondensation of stereoisomeric and ring-chain tautomeric mixture of (+/-)-hydroxylactone 1 and 0.5 equiv of (R)-phenylglycinol. An extension of this methodology was successfully applied to the synthesis of the 5,6-dihydroxy derivative.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Review
Chemistry, Multidisciplinary
Long Min, Li-Ping Zhong, Chuang-Chuang Li
Summary: Steroids continue to play a significant role in organic chemistry, medicinal chemistry, and drug discovery. However, the synthesis of unusual rearranged steroids, particularly abeo-steroids with a medium-sized ring, remains a challenge. This Account summarizes the laboratory's efforts in the total synthesis of abeo-steroids using cycloaddition strategies, highlighting the efficiency and versatility of each strategy in constructing structurally complex abeo-steroid cores. The findings provide valuable insights for advancing the total synthesis of abeo- and related steroids.
ACCOUNTS OF CHEMICAL RESEARCH
(2023)
Article
Chemistry, Applied
Tao Wang, Bo Huang, You-Qing Wang
Summary: Using chiral phosphoric acids as organocatalysts, a formal asymmetric (4+2) cycloaddition of 3-methylene isoindolinone and in situ-generated ortho-quinone methide substrates is achieved. This reaction allows the construction of spiro chroman-isoindolinones containing spiro-N,O-heterocycles with high enantioselectivity, with a broad substrate scope.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Applied
Enrico Marcantonio, Claudio Curti, Lucia Battistini, Andrea Sartori, Luana Cardinale, Giorgio Pelosi, Franca Zanardi
Summary: The remote enolization strategy, strategic exploitation of noncovalent bifunctional organocatalysis, and efficient stereoselective trapping of dienolate intermediates with nitroolefins led to the successful synthesis of functionalized, chiral carbocycle-fused uracils with three contiguous stereocenters in one step, showing good levels of enantioselectivity and complete diastereocontrol. Furthermore, the enantiopure products could be obtained via simple one-cycle recrystallizations and the scaffolds could be further functionalized without losing their chiral integrity.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Review
Biochemistry & Molecular Biology
Arianna Quintavalla, Davide Carboni, Marco Lombardo
Summary: In 1971, a new asymmetric intramolecular aldol reaction catalyzed by the natural amino acid proline was discovered independently by chemists from Hoffmann-La Roche and Schering AG. This reaction later became known as the Hajos-Parrish-Eder-Sauer-Wiechert reaction. In 2000, it was found that L-proline could also catalyze intermolecular aldol reactions with significant enantioselectivities, and in the same year, imidazolidinones derived from natural amino acids were found to efficiently catalyze asymmetric Diels-Alder cycloadditions, marking the birth of modern asymmetric organocatalysis. In 2005, the use of diarylprolinol silyl ethers for the asymmetric functionalization of aldehydes was proposed, further advancing the field of asymmetric organocatalysis.
Article
Chemistry, Multidisciplinary
Dong-Xing Zhu, Jian-Guo Liu, Ming-Hua Xu
Summary: A one-pot reaction has been developed for the stereodivergent synthesis of diverse 2,3-disubstituted dihydrobenzofurans under mild conditions with high yields and stereoselectivity. By appropriate permutations of two chiral catalysts, a wide range of chiral products can be accessed, demonstrating the ability of two chiral catalysts to independently control two contiguous stereogenic centers.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Donglei Wang, Ying-Bo Shao, Yunrong Chen, Xiao-Song Xue, Xiaoyu Yang
Summary: An efficient method for the asymmetric synthesis of planar-chiral macrocycles (paracyclophanes) has been developed using chiral phosphoric acid catalysis for enantioselective electrophilic aromatic aminations with azodicarboxylates. This method allows for the synthesis of a wide range of chiral macrocycles with varying ring sizes and functional groups, achieving high yields and enantioselectivities. The mechanism and origins of the stereoselectivities of these reactions were investigated through experimental studies and computational calculations. Preliminary utilization of the planar-chiral macrocycle as a chiral organocatalyst demonstrated the potential applications of these novel chiral skeletons.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Physical
Chunhui Liu, Ben Bradshaw, Feliu Maseras, Josep Bonjoch, Maria Besora
Article
Plant Sciences
Caroline Bosch, Ben Bradshaw, Josep Bonjoch
JOURNAL OF NATURAL PRODUCTS
(2019)
Article
Chemistry, Organic
Sergi Jansana, Faiza Diaba, Josep Bonjoch
Article
Chemistry, Organic
Mar Saladrigas, Josep Bonjoch, Ben Bradshaw
Review
Chemistry, Organic
Josep Bonjoch, Faiza Diaba
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2020)
Article
Chemistry, Organic
Mar Saladrigas, Jordi Puig, Josep Bonjoch, Ben Bradshaw
Article
Chemistry, Organic
Claudia Marques, Faiza Diaba, Enrique Gomez-Bengoa, Josep Bonjoch
Summary: A synthetic approach to functionalized ABC-tricyclic framework of calyciphilline A-type alkaloids is reported, which involves radical cyclization and stereocontrolled aldol cyclization. The resulting compound serves as a building block for this class of alkaloids, and the synthesis of azatricyclic compound I constitutes a formal synthesis of himalensine A.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Luis Bustos, Carlos Echiburu-Chau, Alejandro Castro-Alvarez, Ben Bradshaw, Mario J. Simirgiotis, Marco Mellado, Claudio Parra, Mauricio Cuellar
Summary: This study determined the cytotoxicity of eleven chalcones synthesized from two acetophenones and investigated their possible mechanisms. Two chalcones showed significant inhibitory effects and are potential candidates for further research and development.
Article
Chemistry, Organic
Laura G. Rodriguez, Ana Delgado, Carlos J. Ciudad, Veronique Noe, Josep Bonjoch, Ben Bradshaw
Summary: A two-step reaction was developed to synthesize a ring system found in natural products. The reaction was explored with eight substituted nitrobenzenes, achieving yields of up to 87%. One of the benzazocine compounds, 4h, exhibited high cytotoxicity and was active against eight cancer cell lines.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Maximiliano Martinez-Cifuentes, Emmanuel Soto-Tapia, Camila Linares-Pipon, Ben Bradshaw, Paulina Valenzuela-Hormazabal, David Ramirez, Patricio Munoz-Torres, Claudio Parra
Summary: This study proposes the design of beta-keto esters as antibacterial compounds. By synthesizing eight beta-keto ester analogues and conducting computational analysis, compound 8 was found to have the most promising potential. In vitro antimicrobial screening showed that compounds 6 and 8 exhibited the most promising activity against the panel of bacteria studied.
Article
Chemistry, Organic
Claudia Marques, Faiza Diaba, Jaume Roca, Josep Bonjoch
Summary: The 5-endo-trig radical cyclization of N-benzyl-N-[(2-substituted)cycloalkenyl] trichloroacetamides using Bu3SnH and AIBN provides access to 3a-methyl- and 3a-methoxycarbonyl enelactams. Diastereoselective enolate alkylation of these enelactams leads to the synthesis of a set of 3-substituted derivatives, which can be further reduced to generate polyfunctionalized cis-octahydroindoles containing three consecutive stereocenters at C-3, C-3a, and C-7a. These building blocks can also be synthesized through an initial reductive radical cyclization using (carbo-substituted)dichloroacetamides.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
