The impact of the steric and electronic factors in both the para-substituted benzaldimine and 2,2-diarylglycine components on the regioselectivity and enantioselectivity of the palladium-catalyzed decarboxylative allylation of allyl 2,2-diarylglycinate aryl imines was explored. These studies revealed that using 2,2-di(2-methoxyphenyl)glycine as the amino acid linchpin allowed for the exclusive synthesis of the desired homoallylic benzophenone imine regioisomers, independent of the nature of the imine moiety, in typically high yields. The resulting enantiomeric ratios, however, are slightly decreased in comparison to the transformations involving the corresponding allyl 2,2-diphenylglycinate imines, but this is more than balanced out by the increases in yield and regioselectivity. Overall, these studies suggest a general strategy for the highly regioselective functionalization of 2-azaallyl anions.
Adenosine
is important for local neuromodulation, and rapid adenosine
signaling can occur spontaneously or after mechanical stimulation,
but little is known about how adenosine is formed in the extracellular
space for those stimulations. Here, we studied mechanically stimulated
and spontaneous adenosine to determine if rapid adenosine is formed
by extracellular breakdown of adenosine triphosphate (ATP) using mice
globally deficient in extracellular breakdown enzymes, either CD39
(nucleoside triphosphate diphosphohydrolase 1, NTPDase1) or CD73 (ecto-5′-nucleotidase).
CD39 knockout (KO) mice have a lower frequency of spontaneous adenosine
events than wild-type (WT, C57BL/6). Surprisingly, CD73KO mice demonstrate
sex differences in spontaneous adenosine; males maintain similar event
frequencies as WT, but females have significantly fewer events and
lower concentrations. Examining the mRNA expression of other enzymes
that metabolize ATP revealed tissue nonspecific alkaline phosphatase
(TNAP) was upregulated in male CD73KO mice, but not secreted prostatic
acid phosphatase (PAP) or transmembrane PAP. Thus, TNAP upregulation
compensates for CD73 loss in males but not in females. These sex differences
highlight that spontaneous adenosine is formed by metabolism of extracellular
ATP by many enzymes. For mechanically stimulated adenosine, CD39KO
or CD73KO did not change stimulation frequency, concentration, or t
1/2. Thus, the mechanism of formation for mechanically
stimulated adenosine is likely direct release of adenosine, different
than spontaneous adenosine. Understanding these different mechanisms
of rapid adenosine formation will help to develop pharmacological
treatments that differentially target modes of rapid adenosine signaling,
and all treatments should be studied in both sexes, given possible
differences in extracellular ATP degradation.
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