An effective Cu-catalyzed
selective formal carboxylation of C–F
bonds with an atmospheric pressure of CO2 is reported.
A variety of gem-difluoroalkenes, gem-difluorodienes, and α-trifluoro-methyl alkenes show high reactivity
and selectivity for this ipso monocarboxylation.
Under mild conditions, diverse important α-fluoroacrylic acids
and α,α-difluorocarboxylates are obtained in good-to-high
yields. Moreover, this operationally simple protocol features good
functional group tolerance, is readily scalable, and the resulting
products are readily converted into bioactive α-fluorinated
carbonyl compounds, indicating potential application in biochemistry
and drug discovery. Mechanistic studies reveal that fluorinated boronate
esters might be vital intermediates in this transformation.
Carbon dioxide (CO ), a well-known greenhouse gas, is also a nontoxic, readily accessible, and renewable one-carbon (C1) source. However, owing to its thermodynamic stability and kinetic inertness, the efficient utilization of CO is challenging. Much effort has been devoted to achieving efficient and selective organic transformations of CO . Recently, the synthesis of important oxazolidin-2-ones from unsaturated amines by using CO has attracted much attention and been heavily studied. This Focus Review presents recent advances in this area by using homogenous catalysis. The cyclization of amines that contain alkynes, alkenes, and allenes with CO is discussed, and possible reaction mechanisms and applications of these transformations are also described.
β-Lactam
antibiotic resistance has become a critical global
health threat. One of the major reasons for drug resistance is the
expression of β-lactamases especially metallo-β-lactamases
such as New Delhi metallo-β-lactamase (NDM-1) by Gram-negative
bacteria. The fungal natural product aspergillomarasmine A (AMA) was
found to be a promising inhibitor of NDM-1 to potentiate currently
used β-lactam antibiotics to overcome drug resistance both in
vitro and in vivo. Although several chemical synthesis and chemoenzymatic
synthesis approaches to access AMA have been reported, the biosynthesis
of AMA was still elusive. Herein, we identified the key enzyme responsible
for the biosynthesis of AMA in Aspergillus oryzae. AMA synthase is a PLP-dependent cysteine synthase homologous protein
which utilizes O-acetyl-l-serine/O-phospho-l-serine and l-aspartic acid
as its substrates. Remarkably, this enzyme catalyzes two consecutive
C–N bond formations to produce AMA efficiently which may be
attributed to the spacious substrate-binding pocket. PLP is covalently
bound to Lys61 by an internal aldimine from the PLP re face, and the si face of PLP pyridine ring is accessible
to the substrates to promote the nucleophilic addition of amino acids
to the double bond of the external adiminine and ultimately to generate
chiral Cα with S configuration.
The catalytic mechanism was proposed based on molecular docking and
biochemical experiments. In addition, we have further investigated
the substrate scope of AMA synthase and identified a variant enzyme
which shows promising potential in producing structurally diverse
molecules containing the C–N bond.
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