Enamine Chemistry. XXVII. Reduction of Enaminones, Enaminothiones and Thioamides by LiAlH4 and NaBH4.

Irreversible Inactivation of Lactate Racemase by Sodium Borohydride Reveals Reactivity of the Nickel–Pincer Nucleotide Cofactor

“…Another noticeable change in the MS spectra of the NaBH 4 -treated enzyme is the appearance of a feature corresponding to the apoenzyme (47 393 Da, Δ−452 Da) for which the signal intensity relative to the major species increased as higher concentrations of NaBH 4 were applied (Figure a). It was reported that NaBH 4 treatment may lead to thioamide bond cleavage or sulfur loss in small molecules . Accordingly, it is conceivable that the thioamide bond linking the NPN cofactor to the lysine residue (K184) was partially disrupted by NaBH 4 treatment, leaving a portion of the enzyme in the apoenzyme state.…”

“…It was reported that NaBH 4 treatment may lead to thioamide bond cleavage or sulfur loss in small molecules. 21 Accordingly, it is conceivable that the thioamide bond linking the NPN cofactor to the lysine residue (K184) was partially disrupted by NaBH 4 treatment, leaving a portion of the enzyme in the apoenzyme state. The reaction of the thioamide bond with hydride may also explain the formation of another minor species with a variable mass in the range of 47 752.5−47 755.5 Da (Δ−92.5 to −89.5 Da); this species may represent the loss of a sulfur atom from the Ni-free major species with additional elimination of an uncertain number of hydrogen atoms (in the range of 1−5, depending on the NaBH 4 concentration).…”

Irreversible inactivation of lactate racemase by sodium borohydride reveals reactivity of the nickel-pincer nucleotide cofactor

“…It was reported that NaBH 4 treatment may lead to thioamide bond cleavage or sulfur loss in small molecules. 12 Accordingly, it is conceivable that the thioamide bond linking the NPN cofactor to the lysine residue (K184) was partially disrupted by NaBH 4 treatment, leaving a portion of the enzyme in the apoenzyme state. The reaction of the thioamide bond with hydride may also explain the formation of another minor species with a variable mass in the range of 47752.5-47755.5 Da (Δ -92.5∼-89.5 Da); this species may represent the loss of a sulfur atom from the Ni-free major species with additional elimination of an uncertain number of hydrogen atoms (in the range of 1-5, depending on the NaBH 4 concentration).…”

“…The reaction of the thioamide bond with hydride may also explain the formation of another minor species with a variable mass in the range of 47752.5-47755.5 Da (Δ -92.5∼-89.5 Da); this species may represent the loss of a sulfur atom from the Ni-free major species with additional elimination of an uncertain number of hydrogen atoms (in the range of 1-5, depending on the NaBH 4 concentration). 12 A scheme depicting these reactions involving the thioamide bond is shown in Figure S3 . Because the signals associated with the apoprotein and the species missing a sulfur atom were much smaller than that of the major Ni-free species, the reactions leading to thioamide bond cleavage and sulfur loss are unlikely to be responsible for LarA Lp inactivation.…”

Stereoselective Synthesis of Nitrogen-Containing Compounds from Enamines

“…To extend the methodology to electrophiles other than imines, we next focused on the reaction of isocyanates. Although the reported method employed N -alkyl or aryl isocyanates, we chose N -tosyl isocyanate ( 8 ) as an analogue of N -sulfonylimines 1 and 6 . First, the sequential ene-type reaction/reduction of 8 with enamine 2a was investigated (eq ).…”