5963-22-4Relevant academic research and scientific papers
Type II flavin-containing monooxygenases: A new class of biocatalysts that harbors baeyer-villiger monooxygenases with a relaxed coenzyme specificity
Riebel, Anette,Fink, Michael J.,Mihovilovic, Marko D.,Fraaije, Marco W.
, p. 1112 - 1117 (2014/05/06)
Within a newly identified set of flavin-containing monooxygenases (FMOs) from Rhodococcus jostii RHA1, we have identified three monooxygenases (FMO-E, FMO-F, and FMO-G) that are effective in catalyzing Baeyer-Villiger oxidations. These type II FMOs display relaxed coenzyme specificity by accepting both NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) and NADH (reduced form of nicotinamide adenine dinucleotide), as a coenzyme, which is a novel and attractive feature among biocatalysts capable of conducting Baeyer-Villiger oxidations. We purified FMO-E and determined that the Michaelis constants for both coenzymes were in the micromolar range, whereas the activity was highest for NADH. By using the stopped-flow technique, formation of a peroxyflavin-enzyme intermediate was observed, which indicated that type II FMOs follow a catalytic mechanism similar to that of other class B flavoprotein monooxygenases. A set of cyclobutanones and cyclohexanones were used to probe the regio- and enantioselectivity of all three recombinant monooxygenases. The biocatalysts readily accepted small cyclic ketones, which enabled the conversion of previously poorly accepted substrates by other monooxygenases (especially norcamphor), and exhibited excellent and unique regio- and enantioselectivities. Sequence analysis revealed that type II FMOs that act as Baeyer-Villiger monooxygenases contain a unique N-terminal domain. Sequence conservation in this protein domain can be used to identify new NADH-dependent Baeyer-Villiger monooxygenases, which would facilitate future biocatalyst discovery efforts. New kid on the block: Members of a newly recognized group of sequence-related flavin-containing monooxygenases can perform Baeyer-Villiger oxidations. Their coenzyme indifference and unique specificity make them attractive biocatalysts.
Metal-catalysed Enantiospecific Aerobic Oxidation of Cyclobutanones
Bolm, Carsten,Schlingloff, Gunther
, p. 1247 - 1248 (2007/10/02)
The metal-catalysed aerobic oxidation of substituted racemic cyclobutanones provides optically active lactones with enantioselectivities of up to 95percent e.e.
Rearrangements in the acid-catalyzed formation of lactones from 2-hydroxynorbornane-2-acetic acid derivatives and related compounds
Yates, Peter,Kaldas, Magdy
, p. 2491 - 2501 (2007/10/02)
A mixture of the epimeric ethyl 2-hydroxynorbornane-2-acetates (1) on treatment with concentrated sulfuric acid is converted in turn to the lactones of exo-2-hydroxynorbornane-1-acetic acid (4), endo-6-hydroxynorbornane-endo-2-acetic acid (5), and exo-3-hydroxynorbornane-exo-2-acetic acid (6).With trifluoroacetic acid or 50percent sulfuric acid, 1 gives 4, but this does not react further.In concentrated sulfuric acid the parent acids of 1 (7) and (E)- and (Z)-(norborn-2-ylidene)acetic acids (8 and 9) and their ethyl esters (10 and 11) give 6 as the infinity product.A mixture of 5-norbornene-endo- and exo-2-acetic acid (30 and 31) on treatment with 50percent sulfuric acid gives 4, 5, 6, and exo-2-hydroxynorbornane-syn-7-acetic acid lactone (33).Routes are proposed for the formation of the lactones that involve protonation and carbocation formation followed by rearrangement via Wagner-Meerwein, endo-6,2-hydride, and exo-3,2-hydride shifts in decreasing order of preference.It is postulated that the usual inhibition of the rearrangement of tertiary to secondary norbornyl carbocations is not operative when the third substituent is a carboxymethyl group or its derivatives because of the electron-withdrawing properties of such groups relative to simple alkyl groups.A preliminary study has shown that exo-5-acetyloxy-endo-2-hydroxynorbornane-exo-2-acetic acid (35) with 50percent sulfuric acid gives four products that are considered to be the γ-lactones of endo-5-acetyloxy- and endo-5-hydroxynorbornane-1-acetic acid (38 and 39) and exo-2-acetyloxy-1-hydroxy- and 1,2-dihydroxynorbornane-syn-7-acetic acid (40 and 41).Protonation of either the hydroxyl or acetyloxyl group is postulated, giving two carbocations that undergo rearrangements as in the case of 1, together with 3,2-hydroxyl shifts.The structures of the lactones are assigned on the basis of spectroscopy, reactivity, and analogy.The reactions of the lactones, which lead to a variety of hydroxy- and oxonorbornaneacetic acids, illustrate their synthetic potential.
CARBOLACTONIZATION OF OLEFINS UNDER MILD CONDITIONS BY CYANOACETIC AND MALONIC ACIDS PROMOTED BY MANGANESE (III) ACETATE
Corey, E. J.,Gross, Andrew W.
, p. 4291 - 4294 (2007/10/02)
A variety of olefins can be converted to γ-lactones with good efficiency by intermolecular carbolactonization using cyanoacetic acid or malonic acid derivatives in the presence of Mn(III) at 23 deg C.
Manganese(III)-Mediated γ-Lactone Annulation
Fristad, William E.,Peterson, John R.
, p. 10 - 18 (2007/10/02)
The annulation of a γ-lactone ring onto an alkene by manganese(III) acetate oxidation of acetic acid was investigated.The regioselectivity of addition to unsymmetrically substituted alkenes is reported along with the stereoselectivity of addition to various acyclic and cyclic alkenes.Alkenes with ionization potentials above 8.2 eV were found to react in good yield.The role of acetic anhydride in these reactions was studied, and it was shown to be oxidized faster than acetic acid and also led to different products.The fate of oxidized acetic acid or anhydridein the absence of suitable acceptor molecule has also been quantitatively identified.The relationship of enolizability, or C-H acidity, of the carboxylic acid being oxidized was established quantitatively.
