Aliphatic C−C Bond Cleavage in α‐Hydroxy Ketones by a Dioxygen‐Derived Nucleophilic Iron–Oxygen Oxidant

Abstract

A nucleophilic iron-oxygen oxidant, formed in situ in the reaction between an iron(II)-benzilate complex and O , oxidatively cleaves the aliphatic C-C bonds of α-hydroxy ketones. In the cleavage reaction, α-hydroxy ketones without any α-C-H bond afford a 1:1 mixture of carboxylic acid and ketone. Isotope labeling studies established that one of the oxygen atoms from dioxygen is incorporated into the carboxylic acid product. Furthermore, the iron(II) complex cleaves an aliphatic C-C bond of 17-α-hydroxyprogesterone affording androstenedione and acetic acid. The O -dependent aliphatic C-C bond cleavage of α-hydroxy ketones containing no α-C-H bond bears similarity to the lyase activity of the heme enzyme, cytochrome P450 17A1 (CYP17A1).

Unraveling the Crucial Role of Single Active Water Molecule in the Oxidative Cleavage of Aliphatic C–C Bond of 2,4′-Dihydroxyacetophenone Catalyzed by 2,4′-Dihydroxyacetophenone Dioxygenase Enzyme: A Quantum Mechanics/Molecular Mechanics Investigation

“…The transformation of (1) to (1A) is predicted to be stabilized by 27.7 kcal/mol on the septet spin surface. Our calculations clearly suggested that the binding of 2,4′-DHAP to the Fe 2+ center is preferred in the anionic form compared to the neutral form which is consistent with the results obtained from the biomimetic studies by Paine’s group. − In (1A), Fe is still not bound with the dioxygen (Fe–O a : ∼ 6 Å). After resolving the coordination preference of 2,4′-DHAP, we moved our attention to the binding of dioxygen to the active metal center.…”

“…4HAP, , and they reported that in the active site of DAD an iron center is directly coordinated to three histidine residues (His76, His78, and His114), and in the close vicinity of the active structure there exists one tyrosine (Tyr93) and one glutamate (Glu108) residue. However, because of the lack of strong experimental evidence, information regarding the actual oxidation state of the catalytic iron center was vague until extensive experimental studies were carried out by Paine and co-workers on the biomimetic models of DAD. − An oxidation state of +2 of iron was first suggested by Paria et al . which was further affirmed through refinement in crystal structure determination at a higher resolution in 2015 .…”

An enzyme-mimic single Fe-N 3 atom catalyst for the oxidative synthesis of nitriles via C─C bond cleavage strategy

“…S16) (41). Then, the C─C bond cleavage of phenylglyoxylic acid (8) produces benzaldehyde ( 9) and simultaneously released CO 2 (42). Last, the ammoxidation of benzaldehyde produced benzonitrile (11).…”

Sesquiterpenes with new carbon skeletons from the basidiomycete Phlebia tremellosa

“…Cytochrome P450 17A1 (CYP17A1) is an example of an enzyme that can cleave α-hydroxy ketones devoid of α-C-H bonds. CYP17A1 is a heme enzyme that catalyzes the cleavage of the C-17 to C-20 bond in 17α-hydroxypregnenolone during the biosynthesis of dehydroepiandrosterone via the ferric peroxo-hemiacetal intermediate [21,22]. Metalloenzymes similar to CYP17A1 seem to be involved even in the biosynthesis of 1.…”