7 research outputs found
Remote Stereoinduction in the Organocuprate-Mediated Allylic Alkylation of Allylic <i>gem</i>-Dichlorides: Highly Diastereoselective Synthesis of (<i>Z</i>)āChloroalkene Dipeptide Isosteres
Highly diastereoselective synthesis
of (<i>Z</i>)-chloroalkene
dipeptide isosteres has been achieved by 1,4-asymmetric induction
in the organocuprate-mediated allylic alkylation adjacent to the chiral
center of allylic <i>gem</i>-dichlorides. The reaction proceeds
with a variety of heterocuprates prepared from CuCN and various organometallic
reagents. It allows rapid construction of valuable architectures of l,d-type and l,l-type (<i>Z</i>)-chloroalkene dipeptide isosteres from the corresponding (<i>E</i>)- and (<i>Z</i>)-allylic <i>gem</i>-dichlorides in high yields, with excellent (<i>Z</i>)-selectivity
and diastereoselectivity
Stereoselective Formation of Trisubstituted (<i>Z</i>)āChloroalkenes Adjacent to a Tertiary Carbon Stereogenic Center by Organocuprate-Mediated Reduction/Alkylation
A robust and efficient method for the synthesis of trisubstituted (<i>Z</i>)-chloroalkenes is described. A one-pot reaction of Ī³,Ī³-dichloro-Ī±,Ī²-enoyl sultams involving organocuprate-mediated reduction/asymmetric alkylation affords Ī±-chiral (<i>Z</i>)-chloroalkene derivatives in moderate to high yields with excellent diastereoselectivity, and allylic alkylation of internal allylic <i>gem</i>-dichlorides is also demonstrated. This study provides the first examples of the use of allylic <i>gem</i>-dichlorides adjacent to the chiral center for novel 1,4-asymmetric induction
Tuning the Catalyst Reactivity of Imidazolylidene Catalysts through Substituent Effects on the <i>N</i>āAryl Groups
A series of imidazolium salts with
various <i>N</i>-aryl
groups were synthesized, and their catalytic activities were evaluated
to investigate the contribution of the <i>N</i>-aryl groups
to the catalytic activity in the synthesis of Ī³-butyrolactone
through an a<sup>3</sup>ād<sup>3</sup>-umpolung addition. Imidazolylidenes
with 2,6-diethylphenyl groups were effective catalysts, and several
mechanistic studies, including a deuterium kinetic isotope effect
study, revealed that both steric and kinetic effects were responsible
for the enhanced catalytic activity
Utilization of the Heavy Atom Effect for the Development of a Photosensitive 8āAzacoumarin-Type Photolabile Protecting Group
A remarkable improvement
of the photochemical properties of coumarin-type
photolabile protecting groups was achieved by iodine substitution.
The newly identified 7-hydroxy-6-iodo-8-azacoumarin (8-aza-Ihc)-caged
acetate showed excellent photolytic efficiency, significantly higher
than that of the corresponding bromine-containing coumarin- and azacoumarin-type
caging groups. The results provide a solid approach to improving the
photosensitivity of photolabile protecting groups
Isostere-Based Design of 8āAzacoumarin-Type Photolabile Protecting Groups: A Hydrophilicity-Increasing Strategy for Coumarin-4-ylmethyls
Described
is the development of 8-azacoumarin-4-ylmethyl groups
as aqueous photolabile protecting groups. A key feature of the strategy
is the isosteric replacement of the C7āC8 enol double bond
of the Bhc derivative with an amide bond, resulting in conversion
of the chromophore from coumarin to 8-azacoumarin. This strategy makes
dramatically enhanced water solubility and facile photocleavage possible
Synthesis and Characterization of Quantum Dot Nanoparticles Bound to the Plant Volatile Precursor of Hydroxy-apo-10ā²-carotenal
This study is focused on the synthesis
and characterization of
hydroxy-apo-10ā²-carotenal/quantum dot (QD) conjugates aiming
at the <i>in vivo</i> visualization of Ī²-ionone, a
carotenoid-derived volatile compound known for its important contribution
to the flavor and aroma of many fruits, vegetables, and plants. The
synthesis of nanoparticles bound to plant volatile precursors was
achieved via coupling reaction of the QD to C<sub>27</sub>-aldehyde
which was prepared from Ī±-ionone via 12 steps in 2.4% overall
yield. The formation of the QD-conjugate was confirmed by measuring
its fluorescence spectrum to observe the occurrence of fluorescence
resonance energy transfer
Cell-Permeable Stapled Peptides Based on HIVā1 Integrase Inhibitors Derived from HIVā1 Gene Products
HIV-1
integrase (IN) is an enzyme which is indispensable for the stable
infection of host cells because it catalyzes the insertion of viral
DNA into the genome and thus is an attractive target for the development
of anti-HIV agents. Earlier, we found Vpr-derived peptides with inhibitory
activity against HIV-1 IN. These Vpr-derived peptides are originally
located in an Ī±-helical region of the parent Vpr protein. Addition
of an octa-arginyl group to the inhibitory peptides caused significant
inhibition against HIV replication associated with an increase in
cell permeability but also relatively high cytotoxicity. In the current
study, stapled peptides, a new class of stabilized Ī±-helical
peptidomimetics were adopted to enhance the cell permeability of the
above lead peptides. A series of stapled peptides, which have a hydrocarbon
link formed by a ruthenium-catalyzed ring-closing metathesis reaction
between successive turns of Ī±-helix, were designed, synthesized,
and evaluated for biological activity. In cell-based assays some of
the stapled peptides showed potent anti-HIV activity comparable with
that of the original octa-arginine-containing peptide (<b>2</b>) but with lower cytotoxicity. Fluorescent imaging experiments revealed
that these stapled peptides are significantly cell permeable, and
CD analysis showed they form Ī±-helical structures, whereas the
unstapled congeners form Ī²-sheet structures. The application
of this stapling strategy to Vpr-derived IN inhibitory peptides led
to a remarkable increase in their potency in cells and a significant
reduction of their cytotoxicity