4 research outputs found
Recommended from our members
Synthesis of ( S)-3-Amino-4-(difluoromethylenyl)-cyclopent-1-ene-1-carboxylic Acid (OV329), a Potent Inactivator of Îł-Aminobutyric Acid Aminotransferase
( S)-3-Amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic acid (OV329, 1) is being developed for the treatment of epilepsy and addiction. The previous 14-step synthesis of OV329 was low yielding, involved an unselective α-elimination to form the cyclopentene, required the use of tert-butyllithium, and produced toxic selenium byproducts in the penultimate step. A new synthesis, which avoids the aforementioned issues, was carried out on large scale, reducing the step count from 14 to 9 steps and increasing the overall yield from 3.7% to 8.1%
Syntheses of Arnottin I and Arnottin II
Short
total syntheses of arnottin I and II were accomplished in
5 and 6 steps, respectively. A sesamol-benzyne cycloaddition with
a 3-furyl-benzoate followed by regiospecific lactonization provided
rapid, large-scale access to the core of arnottin I. Saponification
of arnottin I and hypervalent iodide mediated spirocyclization provided
an efficient and direct preparation of racemic arnottin II
Regiodivergent Addition of Phenols to Allylic Oxides
The regiodivergent addition of substituted
phenols to allylic oxides
has been demonstrated using <i>C</i><sub>2</sub>-symmetric
palladium complexes. Complex phenol donors tyrosine, estradiol, and
griseofulvin follow the predictive model
From TgO/GABA-AT, GABA, and T-263 Mutant to Conception of Toxoplasma
Summary: Toxoplasma gondii causes morbidity, mortality, and disseminates widely via cat sexual stages. Here, we find T. gondii ornithine aminotransferase (OAT) is conserved across phyla. We solve TgO/GABA-AT structures with bound inactivators at 1.55 Å and identify an inactivator selective for TgO/GABA-AT over human OAT and GABA-AT. However, abrogating TgO/GABA-AT genetically does not diminish replication, virulence, cyst-formation, or eliminate cat’s oocyst shedding. Increased sporozoite/merozoite TgO/GABA-AT expression led to our study of a mutagenized clone with oocyst formation blocked, arresting after forming male and female gametes, with “Rosetta stone”-like mutations in genes expressed in merozoites. Mutations are similar to those in organisms from plants to mammals, causing defects in conception and zygote formation, affecting merozoite capacitation, pH/ionicity/sodium-GABA concentrations, drawing attention to cyclic AMP/PKA, and genes enhancing energy or substrate formation in TgO/GABA-AT-related-pathways. These candidates potentially influence merozoite’s capacity to make gametes that fuse to become zygotes, thereby contaminating environments and causing disease