4 research outputs found
Activation of Epoxides by a Cooperative Iron–Thiolate Catalyst: Intermediacy of Ferrous Alkoxides in Catalytic Hydroboration
This
paper describes a cooperative iron–thiolate catalyst
Cp*FeÂ(1,2-Ph<sub>2</sub>PC<sub>6</sub>H<sub>4</sub>S)Â(NCMe) (Cp*<sup>–</sup> = C<sub>5</sub>Me<sub>5</sub><sup>–</sup>,
[<b>1</b>(NCMe)]) for regioselective hydroboration of aryl epoxide
by pinacolborane (HBpin). The critical catalytic step involves the
direct addition of epoxide to the catalyst rather than activation
of the B–H bond of HBpin. Through iron–thiolate cooperation,
[<b>1</b>(NCMe)] opens the aryl epoxide rings affording ferrous–alkoxide
compounds. Notably, the ferrous–alkoxide intermediate (<b>4</b>) was structurally characterized after its isolation from
the reaction of [<b>1</b>(NCMe)] with <i>trans</i>-2,3-diphenyloxirane. The more Lewis acidic hydroboranes such as
H<sub>3</sub>B·THF and 9-BBN (BBN = boraÂbicycloÂnonane)
can also be captured by [<b>1</b>(NCMe)]. The resulting iron–borane
adducts [<b>1</b>HÂ(BH<sub>2</sub>)] and [<b>1</b>HÂ(BBN)]
feature an agnostic Fe···B–H interaction. DFT
calculations indicate that the addition of HBpin across the iron–thiolate
sites is endergonic by 12.9 kcal/mol, whereas it is exergonic by 20.2
kcal/mol with BH<sub>3</sub> and 4.6 kcal/mol with 9-BBN. Combining
the experimental data with theoretical studies, a mechanism of the
substrate activation by [<b>1</b>(NCMe)], followed by HBpin
addition, is proposed for the catalysis
Glycyl Radical Enzymes Catalyzing the Dehydration of Two Isomers of <i>N</i>‑Methyl-4-hydroxyproline
The
various isomers of hydroxyproline (HP) are widely
distributed
in nature, serving as key components of structural proteins, while
their quaternized betaine derivatives function as osmoprotectants
in many organisms. Aerobic bacteria degrade HPs through a variety
of well-studied mechanisms. Recent studies show that certain anaerobic
bacteria degrade HPs through distinct mechanisms, involving the O2-sensitive glycyl radical enzymes (GREs) t4L-HP dehydratase
(HypD) and t4D-HP C–N lyase (HplG). Here, we report the discovery
of two more GREs, N-methyl c4L-HP dehydratase (HpyG)
and N-methyl c4D-HP dehydratase (HpzG), which catalyze
radical-mediated dehydration of the two N-methyl-c4HP
enantiomers, while also displaying significant activities toward their
unmethylated substrates. Both GREs are associated with homologues
of pyrroline-5-carboxylate reductase, which catalyze reduction of
their products N-methyl-pyrroline-5-carboxylate to
form N-methyl-proline. Crystal structures of HpyG
and HpzG in complex with their substrates revealed active site architectures
distinct from that of HypD and provided insights into the mechanism
of enantioselective radical-mediated dehydration. Our research further
expands the repertoire of diverse chemical mechanisms involved in
the bacterial metabolism of highly prevalent HP isomers and derivatives
in the anaerobic biosphere
Glycyl Radical Enzymes Catalyzing the Dehydration of Two Isomers of <i>N</i>‑Methyl-4-hydroxyproline
The
various isomers of hydroxyproline (HP) are widely
distributed
in nature, serving as key components of structural proteins, while
their quaternized betaine derivatives function as osmoprotectants
in many organisms. Aerobic bacteria degrade HPs through a variety
of well-studied mechanisms. Recent studies show that certain anaerobic
bacteria degrade HPs through distinct mechanisms, involving the O2-sensitive glycyl radical enzymes (GREs) t4L-HP dehydratase
(HypD) and t4D-HP C–N lyase (HplG). Here, we report the discovery
of two more GREs, N-methyl c4L-HP dehydratase (HpyG)
and N-methyl c4D-HP dehydratase (HpzG), which catalyze
radical-mediated dehydration of the two N-methyl-c4HP
enantiomers, while also displaying significant activities toward their
unmethylated substrates. Both GREs are associated with homologues
of pyrroline-5-carboxylate reductase, which catalyze reduction of
their products N-methyl-pyrroline-5-carboxylate to
form N-methyl-proline. Crystal structures of HpyG
and HpzG in complex with their substrates revealed active site architectures
distinct from that of HypD and provided insights into the mechanism
of enantioselective radical-mediated dehydration. Our research further
expands the repertoire of diverse chemical mechanisms involved in
the bacterial metabolism of highly prevalent HP isomers and derivatives
in the anaerobic biosphere
Glycyl Radical Enzymes Catalyzing the Dehydration of Two Isomers of <i>N</i>‑Methyl-4-hydroxyproline
The
various isomers of hydroxyproline (HP) are widely
distributed
in nature, serving as key components of structural proteins, while
their quaternized betaine derivatives function as osmoprotectants
in many organisms. Aerobic bacteria degrade HPs through a variety
of well-studied mechanisms. Recent studies show that certain anaerobic
bacteria degrade HPs through distinct mechanisms, involving the O2-sensitive glycyl radical enzymes (GREs) t4L-HP dehydratase
(HypD) and t4D-HP C–N lyase (HplG). Here, we report the discovery
of two more GREs, N-methyl c4L-HP dehydratase (HpyG)
and N-methyl c4D-HP dehydratase (HpzG), which catalyze
radical-mediated dehydration of the two N-methyl-c4HP
enantiomers, while also displaying significant activities toward their
unmethylated substrates. Both GREs are associated with homologues
of pyrroline-5-carboxylate reductase, which catalyze reduction of
their products N-methyl-pyrroline-5-carboxylate to
form N-methyl-proline. Crystal structures of HpyG
and HpzG in complex with their substrates revealed active site architectures
distinct from that of HypD and provided insights into the mechanism
of enantioselective radical-mediated dehydration. Our research further
expands the repertoire of diverse chemical mechanisms involved in
the bacterial metabolism of highly prevalent HP isomers and derivatives
in the anaerobic biosphere