10 research outputs found
The lithiationāborylation reaction:in situ IR spectroscopy studies & automation on a batch platform
Studies on the lithiation, borylation, and 1,2āmetalate rearrangement of Oācycloalkyl 2,4,6ātriisopropylbenzoates
Investigation of the Deprotonative Generation and Borylation of Diamine-Ligated Ī±-Lithiated Carbamates and Benzoates by in situ IR spectroscopy
Diamine-mediated
Ī±-deprotonation of <i>O</i>-alkyl
carbamates or benzoates with alkyllithium reagents, trapping of the
carbanion with organoboron compounds, and 1,2-metalate rearrangement
of the resulting boronate complex are the primary steps by which organoboron
compounds can be stereoselectively homologated. Although the final
step can be easily monitored by <sup>11</sup>B NMR spectroscopy, the
first two steps, which are typically carried out at cryogenic temperatures,
are less well understood owing to the requirement for specialized
analytical techniques. Investigation of these steps by in situ IR
spectroscopy has provided invaluable data for optimizing the homologation
reactions of organoboron compounds. Although the deprotonation of
benzoates in noncoordinating solvents is faster than that in ethereal
solvents, the deprotonation of carbamates shows the opposite trend,
a difference that has its origin in the propensity of carbamates to
form inactive parasitic complexes with the diamine-ligated alkyllithium
reagent. Borylation of bulky diamine-ligated lithiated species in
toluene is extremely slow, owing to the requirement for initial complexation
of the oxygen atoms of the diol ligand on boron with the lithium ion
prior to boronālithium exchange. However, ethereal solvent,
or very small amounts of THF, facilitate precomplexation through initial
displacement of the bulky diamines coordinated to the lithium ion.
Comparison of the carbonyl stretching frequencies of boronates derived
from pinacol boronic esters with those derived from trialkylboranes
suggests that the displaced lithium ion is residing on the pinacol
oxygen atoms and the benzoate/carbamate carbonyl group, respectively,
explaining, at least in part, the faster 1,2-metalate rearrangements
of boronates derived from the trialkylboranes
Synthesis and biological evaluation of (E)-4-hydroxy-3-methylbut2-enyl phosphate (HMBP) aryloxy triester phosphoramidate Prdrugs as activators of VĪ³9/VĪ“2 T-cells immune response
The aryloxy triester phosphoramidate prodrug approach has been used with success in drug discovery. Herein, we describe the first application of this prodrug technology to the monophosphate derivative of the phosphoantigen HMBPP and one of its analogues. Some of these prodrugs exhibited specific and potent activation of VĪ³9/VĪ“2 T-cells, which were then able to lyse bladder cancer cells in vitro. This work highlights the promise of this prodrug technology in the discovery of novel immunotherapeutics
Stereospecific Conversion of Boronic Esters into Enones using Methoxyallene:Ā Application in the Total Synthesis of 10āDeoxymethynolide
Synthesis and Biological Evaluation of (E)4-Hydroxy-3-methylbut-2-enyl Phosphate (HMBP) Aryloxy Triester Phosphoramidate Prodrugs as Activators of V9/V2 TCell Immune Responses
Synthesis and Biological Evaluation of (<i>E</i>)ā4-Hydroxy-3-methylbut-2-enyl Phosphate (HMBP) Aryloxy Triester Phosphoramidate Prodrugs as Activators of VĪ³9/VĪ“2 TāCell Immune Responses
The aryloxy triester
phosphoramidate prodrug approach has been
used with success in drug discovery. Herein, we describe the first
application of this prodrug technology to the monophosphate derivative
of the phosphoantigen HMBPP and one of its analogues. Some of these
prodrugs exhibited specific and potent activation of VĪ³9/VĪ“2
T-cells, which were then able to lyse bladder cancer cells in vitro.
This work highlights the promise of this prodrug technology in the
discovery of novel immunotherapeutics
Synthesis and Biological Evaluation of (<i>E</i>)ā4-Hydroxy-3-methylbut-2-enyl Phosphate (HMBP) Aryloxy Triester Phosphoramidate Prodrugs as Activators of VĪ³9/VĪ“2 TāCell Immune Responses
The aryloxy triester
phosphoramidate prodrug approach has been
used with success in drug discovery. Herein, we describe the first
application of this prodrug technology to the monophosphate derivative
of the phosphoantigen HMBPP and one of its analogues. Some of these
prodrugs exhibited specific and potent activation of VĪ³9/VĪ“2
T-cells, which were then able to lyse bladder cancer cells in vitro.
This work highlights the promise of this prodrug technology in the
discovery of novel immunotherapeutics