Large Scale Synthesis of an Ampakine-type Active Pharmaceutical Ingredient Based on a Telescoped Regioselective Double Amidation Reaction

Hardouin, Christophe; Pin, Frederic; Giffard, Jean-François; Hervouet, Yvon; Hublet, Julie; Janvier, Solenn; Penloup, Christine; Picard, Julien; Pinault, Nathalie; Schiavi, Bruno; Zhang, Peng; Zhao, Weiwei; Zhu, Xueyan

doi:10.1021/acs.oprd.9b00241

Cited by 5 publications

(2 citation statements)

References 26 publications

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“…Facile Pinnick oxidation allowed us to explore cyclization strategies, which required extensive optimization due to the buildup of strain resulting from electron repulsion between nonbonding orbitals on the three oxygen atoms that line the northern border (see X-ray of 9 for dihedral angles). The use of ClCH 2 Br was ultimately successful, while alternative procedures that relied on CH 2 Br 2 , FCH 2 I, formaldehyde, or trioxane/Brønsted or Lewis acids all failed. Radical C–H bromination occurred smoothly to deliver 9 on gram-scale.…”

mentioning

confidence: 99%

Iron-Catalyzed Hydrobenzylation: Stereoselective Synthesis of (−)-Eugenial C

Gan,

Kotesova,

Castanedo

et al. 2023

J. Am. Chem. Soc.

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Metal-hydride hydrogen atom transfer (MHAT) has emerged as a useful tool to form quaternary carbons from alkenes via hydrofunctionalization. Methods to date that cross-couple alkenes with sp3 partners rely on heterobimetallic catalysis to merge the two cycles. Here, we report an iron-only cross-coupling via putative MHAT/SH2 steps that solves a key stereochemical problem in the synthesis of meroterpenoid eugenial C and obviates the need for nickel. The concise synthesis benefits from a conformationally locked o,o′-disubstituted benzyl bromide and a locally sourced chiral pool terpene coupling partner.

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confidence: 99%

Iron-Catalyzed Hydrobenzylation: Stereoselective Synthesis of (−)-Eugenial C

Gan,

Kotesova,

Castanedo

et al. 2023

J. Am. Chem. Soc.

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“…Finally, we comment on the conditions proposed by the software, especially on the usability of certain reagents at large scales. The reader will, no doubt, recognize many conditions used widely on industrial scales – for instance, the use of H 2 /Pd 19 , 20 in pathways 5 , 6 , 10 , 14 , and 15 or PTC 21 in pathways 5 , 6 , 7 , 9 , 15 , and 23 . On the other hand, the uses of reagents such as TEMPO, n -BuLi or LAH merit further discussion.…”

Section: Resultsmentioning

confidence: 99%

Computer-generated “synthetic contingency” plans at times of logistics and supply problems: scenarios for hydroxychloroquine and remdesivir

et al. 2020

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Practical and Selective Syntheses of S‐Acyl and N‐Acyl Glutathiones with N‐Acyl Imidazoles in Water

Retini,

Sisti,

Olivieri

et al. 2024

Eur J Org Chem

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A selective, mild, convenient, and green protocol for the preparation of S‐acyl and N‐acyl glutathiones is described involving the chemical modification of glutathione (GSH) with N‐acyl imidazoles at room temperature in water. The syntheses of S‐acyl glutathiones were achieved in very high yields using 1 equiv of an N‐acyl imidazole in water at room temperature, without the need of a base. Double acylation of GSH with various N‐acyl imidazoles in weakly basic aqueous media in the presence of N‐hydroxysuccinimide (HOSu) as the activating reagent followed by selective deprotection of the S‐acyl group with aqueous ammonia at room temperature gave high yields of N‐acyl glutathiones. Moreover, the reaction could accommodate a diverse range of carboxylic acids such as (hetero)benzoic acids, phenylacetic acids, aliphatic acids from short‐chain fatty acids (including acetic acid), long‐chain polyunsaturated fatty acids, secondary or tertiary amino acids, and carboxylic acids containing clickable functional groups, fluorescent probes, or drugs.

show abstract

Large Scale Synthesis of an Ampakine-type Active Pharmaceutical Ingredient Based on a Telescoped Regioselective Double Amidation Reaction

Cited by 5 publications

References 26 publications

Iron-Catalyzed Hydrobenzylation: Stereoselective Synthesis of (−)-Eugenial C

Iron-Catalyzed Hydrobenzylation: Stereoselective Synthesis of (−)-Eugenial C

Computer-generated “synthetic contingency” plans at times of logistics and supply problems: scenarios for hydroxychloroquine and remdesivir

Practical and Selective Syntheses of S‐Acyl and N‐Acyl Glutathiones with N‐Acyl Imidazoles in Water

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