Total syntheses of the parvistemoline alkaloids enabled by stereocontrolled Ir/Pd-catalyzed allylic alkylation.

The functionalized polycycle with densely contiguous tertiary stereocenters is a formidable challenge in synthesizing the parvistemoline family of Stemona alkaloids. We herein report their catalytic, asymmetric total syntheses in 13-14 steps from commercially available 2-(methoxycarbonyl)-pyrrole, featuring the development and deployment of an Ir/Pd-synergistically-catalyzed allylation of α-non-substituted keto esters with secondary aryl-substituted alcohols, stereodivergently accessible to four stereoisomers. Using chiral Pd-enolate and Ir π-allyl complex under neutral conditions, no epimerization occurs.

Total Syntheses of Cinchona Alkaloids via Photoredox-Catalyzed Deoxygenative Arylation.

Metallaphotoredox-enabled deoxygenative arylation of alcohols is a recently developed robust synthetic strategy for sp-sp coupling by MacMillan. Inspired by this method, we report herein its first utilization in natural product total synthesis through realizing the coupling of 4-bromo-quinoline or 4-bromo-6-methoxyquinoline with quincorine or quincoridine, respectively. The alcohols were de novo synthesized in racemic form by a key step of the intramolecular Diels-Alder reaction or in an enantioselective manner by Ir/amine dual-catalyzed allylation.

Targeting endothelial tight junctions to predict and protect thoracic aortic aneurysm and dissection.

Aims: Whether changes in endothelial tight junctions (TJs) lead to the formation of thoracic aortic aneurysm and dissection (TAAD) and serve as an early indicator and therapeutic target remains elusive.

Methods And Results: Single-cell RNA sequencing analysis showed aberrant endothelial TJ expressions in the thoracic aortas of patients with TAAD. In a β-aminopropionitrile (BAPN)-induced TAAD mouse model, endothelial TJ function was disrupted in the thoracic aortas at an early stage (5 and 10 days) as observed by a vascular permeability assay, while the intercellular distribution of crucial TJ components was significantly decreased by en face staining.