Duncan C. Ellinwood

Rapid Development and First GMP Manufacture of AMPKγ3 Activator PF-07293893

Jocelyn L. Baer, Thomas A. Brandt, Adam R. Brown, John M. Curto et autres

We report the development and scale-up of a first-generation route to PF-07293893, an AMPKγ3 activator for the treatment of heart failure. The synthesis includes a metal-catalyzed C–N coupling, a telescoped N -Boc deprotection/amidation sequence, and a final recrystallization. Strategic process optimization addressed …

us (code pays fourni par la source)

Substrate Promiscuity of a Paralytic Shellfish Toxin Amidinotransferase

April L. Lukowski, Leena Mallik, Meagan E. Hinze, Brian M. Carlson et autres

Secondary metabolites are assembled by enzymes that often perform reactions with high selectivity and specificity. Many of these enzymes also tolerate variations in substrate structure, exhibiting promiscuity that enables various applications of a given biocatalyst. However, initial enzyme characterization studies frequently do …

us (code pays fourni par la source)

C–H Hydroxylation in Paralytic Shellfish Toxin Biosynthesis

April L. Lukowski, Duncan C. Ellinwood, Meagan E. Hinze, Ryan J. DeLuca et autres

The remarkable degree of synthetic selectivity found in Nature is exemplified by the biosynthesis of paralytic shellfish toxins such as saxitoxin. The polycyclic core shared by saxitoxin and its relatives is assembled and subsequently elaborated through the installation of hydroxyl groups with …

us, th (code pays fourni par la source)

Functionalized cyclopentanes via Sc(III)-catalyzed intramolecular enolate alkylation

Christopher C. McAtee, Duncan C. Ellinwood, Rory C. McAtee, Corinna S. Schindler

us (code pays fourni par la source)

Total synthesis of [13C]2‐, [13C]3‐, and [13C]5‐isotopomers of xanthohumol, the principal prenylflavonoid from hops

Duncan C. Ellinwood, Mohamed F. El‐Mansy, Layhna S. Plagmann, Jan Frederik Stevens et autres

Xanthohumol [(E)‐6′‐methoxy‐3′‐(3‐methylbuten‐2‐yl)‐2′,4′,4″‐trihydroxychalcone], he principal prenylated flavonoid from hops, has a complex bioactivity profile, and 13C‐labeled isotopomers of this compound are of potential use as molecular probes and as analytical standards to study metabolism and mode of action. 1,3‐[13C]2‐Xanthohumol was prepared by an …

us, Égypte (code pays fourni par la source)