2 research outputs found
Experimental and Computational Gas Phase Acidities of Conjugate Acids of Triazolylidene Carbenes: Rationalizing Subtle Electronic Effects
In
recent years, triazolylidene carbenes have come to the forefront
as important organocatalysts for a wide range of reactions. The fundamental
properties of these species, however, remain largely unknown. Herein,
the gas phase acidities have been measured and calculated for a series
of triazolium cations (the conjugate acids of the triazolylidene carbenes)
that have not been heretofore examined in vacuo. The results are discussed
in the context of these species as catalysts. We find correlations
between the gas phase acidity and selectivity in two <i>Umpolung</i> reactions catalyzed by these species; such correlations are the
first of their kind. We are able to use these linear correlations
to improve reaction enantioselectivity. These results establish the
possibility of using these thermochemical properties to predict reactivity
in related transformations
Synthesis and Biological Evaluation of 1α,25-Dihydroxyvitamin D<sub>3</sub> Analogues with a Long Side Chain at C12 and Short C17 Side Chains
Structure-guided optimization was used to design new
analogues
of 1α,25-dihydroxyvitamin D<sub>3</sub> bearing the main side
chain at C12 and a shorter second hydroxylated chain at C17. The new
compounds <b>5a</b>–<b>c</b> were efficiently synthesized
from ketone <b>9</b> (which is readily accessible from the Inhoffen–Lythgoe
diol) with overall yields of 15%, 6%, and 3% for <b>5a</b>, <b>5b</b>, and <b>5c</b>, respectively. The triene system was
introduced by the Pd-catalyzed tandem cyclization–Suzuki coupling
method. The new analogues were assayed against human colon and breast
cancer cell lines and in mice. All new vitamin D<sub>3</sub> analogues
bound less strongly to the VDR than 1α,25-dihydroxyvitamin D<sub>3</sub> but had similar antiproliferative, pro-differentiating, and
transcriptional activity as the native hormone. In vivo, the three
analogues had markedly low calcemic effects