Ir-Catalyzed Asymmetric Hydrogenation of -Fused Heteroarenes with High Nitrogen Density: An Access to Chiral 2,5-Disubstituted 5,6-Dihydropyrrolo[1,2-][1,2,4]triazolo[5,1-]pyrazines.

A highly enantioselective Ir-catalyzed asymmetric hydrogenation of 2,5-disubstituted pyrrolo[1,2-][1,2,4]triazolo[5,1-]pyrazines containing four nitrogen atoms has been first realized. Under additive-free conditions, a variety of chiral 2,5-disubstituted 5,6-dihydropyrrolo[1,2-][1,2,4]triazolo[5,1-]pyrazines can be afforded in high yields (86-98%) with excellent enantioselectivities of up to 99% ee. This method provides a straightforward strategy for the efficient synthesis of chiral multinitrogen polyheterocyclic compounds.

Iridium-Catalyzed Asymmetric Hydrogenation of Heteroaromatics with Multiple N Atoms via Substrate Activation: An Entry to 4,5,6,7-Tetrahydropyrazolo[1,5-]pyrimidine-3-carbonitrile Core of a Potent BTK Inhibitor.

The chiral 4,5,6,7-tetrahydropyrazolo[1,5-]pyrimidine is the key core skeleton of potent Bruton's tyrosine kinase (BTK) inhibitor Zanubrutinib, and the catalyst-controlled asymmetric hydrogenation of planar multinuclear pyrimidine heteroarenes with multiple N atoms could provide an efficient route toward its synthesis. Owing to the strong aromaticity and poisoning effect toward chiral transition metal catalyst, asymmetric hydrogenation of pyrazolo[1,5-]pyrimidines with multiple nitrogen atoms is still a challenge for synthesizing the chiral 4,5,6,7-tetrahydropyrazolo[1,5-]-pyrimidine. Herein, an efficient iridium-catalyzed asymmetric hydrogenation of pyrazolo[1,5-]pyrimidines has been developed using substrate activation strategy, with up to 99% ee.

Marinobufagenin levels in preeclamptic patients: a preliminary report.

Preeclampsia is a disorder resulting in significant fetomaternal complications with no definitive pharmacological intervention. A bufadienolide, marinobufagenin, has been implicated in the etiology of preeclampsia. We investigated both the blood and urine levels of marinobufagenin in preeclamptic and control subjects.

A chemifluorescent immunoassay for the determination of marinobufagenin in body fluids.

We describe here the development of a chemifluorescent competitive enzyme-linked immunosorbent assay (ELISA) that quantifies marinobufagenin (MBG) levels in biological fluids. Based on a polyclonal antibody raised against a novel MBG-bovine serum albumin conjugate, this assay achieved an MBG detection limit of less than 9 pg/mL. MBG levels in various rat urine and serum samples were effectively determined using this methodology.

Ceragenins: cholic acid-based mimics of antimicrobial peptides.

The prevalence of drug-resistant bacteria drives the quest for new antimicrobials, including those that are not expected to readily engender resistance. One option is to mimic Nature's most ubiquitous means of controlling bacterial growth, antimicrobial peptides, which have evolved over eons. In general, bacteria remain susceptible to these peptides.