Copper‐Catalyzed Semi‐Reduction of Alkynes

Cox, Nick; Dang, Hester; Whittaker, Aaron M.; Lalić, Gojko

doi:10.1002/0471264229.os093.28

Cited by 2 publications

(1 citation statement)

References 33 publications

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“…Alkyne 2 (10.6 g, 49.9 mmol) was reduced according to protocols adapted from Cox et al Crude material was purified by silica gel chromatography (hexanes/EtOAc, 0 → 30%) to afford alkene 3 (9.97 g, 46.5 mmol, 93%) as a clear, viscous oil. The flash column chromatography removed ca.…”

Section: Methodsmentioning

confidence: 99%

High-Affinity Alkynyl Bisubstrate Inhibitors of Nicotinamide N-Methyltransferase (NNMT)

et al. 2019

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Nicotinamide N-methyltransferase (NNMT) is a metabolic enzyme responsible for the methylation of nicotinamide (NAM) using cofactor S-adenosylmethionine (SAM). NNMT overexpression has been linked to diabetes, obesity, and a variety of cancers. Successful development of potent and selective NNMT inhibitors could further reveal the role of NNMT in various diseases, potentially enabling new treatments for metabolic disorders and several cancers. In this work, structure-based rational design led to the development of potent and selective alkynyl bisubstrate inhibitors of NNMT. The reported nicotinamide-SAM conjugate (named NS1) features an alkyne as a key design element that closely mimics the linear, 180°transition state geometry found in the NNMT-catalyzed SAM → NAM methyl transfer reaction. NS1 was synthesized as a single enantiomer and diastereomer in 14 steps and found to be a high-affinity, subnanomolar NNMTinhibitor. An X-ray co-crystal structure and structure-activity relationship (SAR) study revealed the unique ability of an alkynyl linker to span the methyl transfer tunnel of NNMT with ideal shape complementarity.

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Section: Methodsmentioning

confidence: 99%

High-Affinity Alkynyl Bisubstrate Inhibitors of Nicotinamide N-Methyltransferase (NNMT)

et al. 2019

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Diboron-Assisted Copper-Catalyzed Z-Selective Semihydrogenation of Alkynes Using Ethanol as a Hydrogen Donor

et al. 2019

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We herein describe a B2Pin2-assisted copper-catalyzed semihydrogenation of alkynes. A variety of alkenes were obtained in good to excellent yields with Z-selectivity under mild reaction conditions. Mechanistic studies indicated that a transfer hydrogenation process was involved and ethanol acted as both a solvent and a hydrogen donor in this reaction. The present protocol enabled convenient synthesis of deuterium-substituted Z-alkenes such as Z-Combretastain A4-d 2 in a high deuteration ratio by using readily available ethanol-d 1 as the deuterium source.

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Copper‐Catalyzed Semi‐Reduction of Alkynes

Cited by 2 publications

References 33 publications

High-Affinity Alkynyl Bisubstrate Inhibitors of Nicotinamide N-Methyltransferase (NNMT)

High-Affinity Alkynyl Bisubstrate Inhibitors of Nicotinamide N-Methyltransferase (NNMT)

Diboron-Assisted Copper-Catalyzed Z-Selective Semihydrogenation of Alkynes Using Ethanol as a Hydrogen Donor

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