5 research outputs found
Rapid Biomolecular Trifluoromethylation Using Cationic Aromatic Sulfonate Esters as Visible-Light-Triggered Radical Photocages
Described here is a photodecaging approach to radical
trifluoromethylation
of biomolecules. This was accomplished by designing a quinolinium
sulfonate ester that, upon absorption of visible light, achieves decaging
via photolysis of the sulfonate ester to ultimately liberate free
trifluoromethyl radicals that are trapped by π-nucleophiles
in biomolecules. This photodecaging process enables protein and protein-interaction
mapping experiments using trifluoromethyl radicals that require only
1 s reaction times and low photocage concentrations. In these experiments,
aromatic side chains are labeled in an environmentally dependent fashion,
with selectivity observed for tryptophan (Trp), followed by histidine
(His) and tyrosine (Tyr). Scalable peptide trifluoromethylation through
photodecaging is also demonstrated, where bespoke peptides harboring
trifluoromethyl groups at tryptophan residues can be synthesized with
5–7 min reaction times and good yields
Enantioselective Synthesis of Cyclobutanes via Sequential Rh-catalyzed Bicyclobutanation/Cu-catalyzed Homoconjugate Addition
Enantiomerically
enriched cyclobutanes are constructed by a three-component process
in which <i>t</i>-butyl (<i>E</i>)-2-diazo-5-arylpent-4-enoates
are treated with Rh<sub>2</sub>(<i>S</i>-NTTL)<sub>4</sub> to provide enantiomerically enriched bicyclobutanes, which can subsequently
engage in homoconjugate addition/enolate trapping sequence to give
densely functionalized cyclobutanes with high diastereoselectivity.
This three-component, two-catalyst procedure can be carried out in
a single flask. Rh<sub>2</sub>(<i>S</i>-NTTL)<sub>4</sub>-catalyzed reaction of <i>t</i>-butyl (<i>Z</i>)-2-diazo-5-phenylpent-4-enoate gives the Büchner cyclization
product in excellent enantioselectivity
Enantioselective Synthesis of Cyclobutanes via Sequential Rh-catalyzed Bicyclobutanation/Cu-catalyzed Homoconjugate Addition
Enantiomerically
enriched cyclobutanes are constructed by a three-component process
in which <i>t</i>-butyl (<i>E</i>)-2-diazo-5-arylpent-4-enoates
are treated with Rh<sub>2</sub>(<i>S</i>-NTTL)<sub>4</sub> to provide enantiomerically enriched bicyclobutanes, which can subsequently
engage in homoconjugate addition/enolate trapping sequence to give
densely functionalized cyclobutanes with high diastereoselectivity.
This three-component, two-catalyst procedure can be carried out in
a single flask. Rh<sub>2</sub>(<i>S</i>-NTTL)<sub>4</sub>-catalyzed reaction of <i>t</i>-butyl (<i>Z</i>)-2-diazo-5-phenylpent-4-enoate gives the Büchner cyclization
product in excellent enantioselectivity
Enantioselective Synthesis of Cyclobutanes via Sequential Rh-catalyzed Bicyclobutanation/Cu-catalyzed Homoconjugate Addition
Enantiomerically
enriched cyclobutanes are constructed by a three-component process
in which <i>t</i>-butyl (<i>E</i>)-2-diazo-5-arylpent-4-enoates
are treated with Rh<sub>2</sub>(<i>S</i>-NTTL)<sub>4</sub> to provide enantiomerically enriched bicyclobutanes, which can subsequently
engage in homoconjugate addition/enolate trapping sequence to give
densely functionalized cyclobutanes with high diastereoselectivity.
This three-component, two-catalyst procedure can be carried out in
a single flask. Rh<sub>2</sub>(<i>S</i>-NTTL)<sub>4</sub>-catalyzed reaction of <i>t</i>-butyl (<i>Z</i>)-2-diazo-5-phenylpent-4-enoate gives the Büchner cyclization
product in excellent enantioselectivity
Genetically Encoded Tetrazine Amino Acid Directs Rapid Site-Specific <i>in Vivo</i> Bioorthogonal Ligation with <i>trans</i>-Cyclooctenes
Bioorthogonal ligation methods with improved reaction
rates and
less obtrusive components are needed for site-specifically labeling
proteins without catalysts. Currently no general method exists for <i>in vivo</i> site-specific labeling of proteins that combines
fast reaction rate with stable, nontoxic, and chemoselective reagents.
To overcome these limitations, we have developed a tetrazine-containing
amino acid, <b>1</b>, that is stable inside living cells. We
have site-specifically genetically encoded this unique amino acid
in response to an amber codon allowing a single <b>1</b> to
be placed at any location in a protein. We have demonstrated that
protein containing <b>1</b> can be ligated to a conformationally
strained <i>trans</i>-cyclooctene <i>in vitro</i> and <i>in vivo</i> with reaction rates significantly faster
than most commonly used labeling methods