Adventures in Atropisomerism: Total Synthesis of a Complex Active Pharmaceutical Ingredient with Two Chirality Axes

Beutner, Gregory L.; Carrasquillo‐Flores, Ronald; Geng, Peng; Hsiao, Yi; Huang, Eric C.; Janey, Jacob M.; Katipally, Kishta; Kolotuchin, Sergei; Porte, Thomas La; Lee, Andrew; Lobben, Paul C.; Gonzalez, Federico Lora; Mack, Brendan; Mudryk, Boguslaw; Qiu, Yuping; Qian, Xinhua; Ramı́rez, Antonio; Razler, Thomas M.; Rosner, Thorsten; Shi, Zugui; Simmons, Eric M.; Stevens, Jason M.; Wang, Jianji; Wei, Carolyn S.; Wisniewski, Steven R.; Zhu, Ye

doi:10.1021/acs.orglett.8b01218

Cited by 52 publications

(37 citation statements)

References 43 publications

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“…Chirality has also become increasingly important in pharmaceutical science and industry on the design, discovery, and development of drugs for enhancing their potency and selectivity [5,6]. In this regard, asymmetric and catalytic synthesis of chiral compounds have been actively pursued for more than half a century to meet the needs of chemical and biomedical research [7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Among the numerous chiral biomolecules and their complexes, DNA has attracted special attention in the chemistry community because it shows multilayer paired chirality along with their double-or single-strand and i-Motif backbones (Figure 1(a)) [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Multilayer 3D Chirality and Its Synthetic Assembly

Liu

Yang

et al. 2019

Research

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3D chirality of sandwich type of organic molecules has been discovered. The key element of this chirality is characterized by three layers of structures that are arranged nearly in parallel fashion with one on top and one down from the center plane. Individual enantiomers of these molecules have been fully characterized by spectroscopies with their enantiomeric purity measured by chiral HPLC. The absolute configuration was unambiguously assigned by X-ray diffraction analysis. This is the first multilayer 3D chirality reported and is anticipated to lead to a new research area of asymmetric synthesis and catalysis and to have a broad impact on chemical, medicinal, and material sciences in future.

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Section: Introductionmentioning

confidence: 99%

Multilayer 3D Chirality and Its Synthetic Assembly

Liu

Yang

et al. 2019

Research

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“…Among them, 7m represents the part structure of the Bruton's tyrosine kinase (BTK) inhibitor, which is currently in phase 2 clinical trials for the treatment of rheumatoid arthritis. 18 Scheme 7 Scale-up reactions.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…To improve the efficiency of the reaction, various combinations of Ir and Ni catalysts were evaluated, however, no en-couraging results were obtained (entries [12][13][14][15][16]. The variation of the catalyst loading, changing the leaving groups to acetate or benzoate, and modifying the N-protecting group did not provide any better result (entries [17][18][19][20][21].…”

mentioning

confidence: 99%

C(sp3)–H Activation Enabled by (η3-Indolylmethyl)palladium Complexes: Synthesis of Monosubstituted Tetrahydrocarbazoles

Kumar¹,

Vivekanand²,

Singh³

et al. 2021

Synthesis

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The synthesis of monosubstituted tetrahydrocarbazoles is achieved via the palladium-catalyzed formal [4+2]-cycloaddition of 2-alkyl-3-indolylmethyl carbonates and monosubstituted olefins. The transformation demonstrates an unusual C(sp3)-H activation enabled by (η3-indolylmethyl)palladium complexes. The regioselectivity is found to be dependent on the nature of the substituent across the olefin component. Elaborate mechanistic studies are performed, and the synthetic utility of the products is also demonstrated.

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“…The most active compound 33 ultimately possesses a classical stereocenter and two stereodefined stereogenic axes. The latter has been subsequently prepared in an atroposelective and effective way , …”

Section: Atropisomerismmentioning

confidence: 99%

Stereochemistry and Recent Applications of Axially Chiral Organic Molecules

et al. 2020

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This minireview covers the literature of the last decade related to the stereochemistry of axially chiral molecules. The first section reviews the use of dynamic NMR and dynamic HPLC for the ranking of the steric size of common organic moieties. The second and third sections describe the recent advances in the preparation of new atropisomeric scaffolds, and in the asymmetric synthesis of stereogenic axes by means of atroposelective organocatalysis.

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Adventures in Atropisomerism: Total Synthesis of a Complex Active Pharmaceutical Ingredient with Two Chirality Axes

Abstract: A strategy to prepare compounds with multiple chirality axes, which has led to a concise total synthesis of compound 1A with complete stereocontrol, is reported.

Cited by 52 publications

References 43 publications

Multilayer 3D Chirality and Its Synthetic Assembly

Multilayer 3D Chirality and Its Synthetic Assembly

C(sp3)–H Activation Enabled by (η3-Indolylmethyl)palladium Complexes: Synthesis of Monosubstituted Tetrahydrocarbazoles

Stereochemistry and Recent Applications of Axially Chiral Organic Molecules

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