We describe a convergent, base-free two-step synthesis of 1,3-diketones and β-ketoesters from α-diazocarbonyl compounds, trialkylboranes, and aromatic aldehydes in a three-component process. The synthetic potential of this protocol was underscored by the synthesis of several symmetrical 1,3,5-triaryl-4-alkyl and 1,3,4,5-tetraryl substituted pyrazoles in a three-step sequence.

Dedicated to Dr. Joseph M. Muchowski on the occasion of his 82^nd birthday A general strategy for the facile construction of both the ABDE and ABCD cores of tronocarpine, chippiine and dippinine alkaloids through the retrosynthetic disconnection of the polycyclic motifs into an indole or tryptamine fragment and a suitably functionalized alkyl chain is presented. The approach is enabled by an efficient Ir(III)-catalyzed, photoredox-mediated radical addition of tetramethyl 1-bromopentane-1,1,3,5-tetracarboxylate and dimethyl 2-bromopentanedioate selectively at C-2 of the indole. Subsequent intramolecular cyclization events furnish the desired ABDE and ABCD polycyclic cores in good preparative yields.

Pulmonary fibrosis (PF) is characterized by excessive collagen deposition and impaired lung function. Pulmonary surfactant may modulate fibroblast activity and offer therapeutic benefits. We developed a natural porcine pulmonary surfactant (NPPS) enriched with 1,2-dipalmitoyl-rac-glycero-3-phosphatidylethanolamine (PE) and evaluated its biophysical and biological properties. Biophysical analysis showed that PE improved surfactant performance by increasing surface pressure and stability. In vitro, NPPS-PE reduced collagen expression and induced apoptosis in normal human lung fibroblasts; in addition, it decreased proliferation in fibroblasts stimulated with TGF-β. In vivo, NPPS-PE improved gas exchange and significantly reduced collagen deposition in bleomycin-treated mice. These findings suggest that NPPS-PE may be a promising therapeutic strategy for fibrosing lung diseases.

The phospholipid 1,2-dipalmitoyl-rac-glycero-3-phosphatidylethanolamine (PE) comprises two fatty acid chains: glycerol, phosphate, and ethanolamine. PE participates in critical cellular processes such as apoptosis and autophagy, which places it as a target for designing new therapeutic alternatives in diseases such as pulmonary fibrosis. Therefore, this study aimed obtain PE through a six-step organic synthesis pathway and determine its biological effect on apoptosis induction in normal human lung fibroblasts (NHLF). The first step of the organic synthesis route began with protected glycerol that was benzylated at sn-3; later, it was deprotected to react with palmitic acid at sn-1, sn-2. To remove the benzyl group, hydrogenation was performed with palladium on carbon (Pd/C); subsequently, the molecule was phosphorylated in sn-3 with phosphorus oxychloride and triethylamine, and the intermediate was hydrolyzed in an acid medium to obtain the final compound. After PE synthesis, apoptosis assessment was performed: apoptosis was induced using exposure to annexin V-FITC/propidium iodide-ECD (PI) and quantified using flow cytometry. The experiments were performed in three NHLF cell lines with different concentrations of PE 10, 100 and 1000µg/mL for 24 and 48hours. The PE obtained by organic synthesis presented a melting point of 190-192 °C, a purity of 95%, and a global yield of 8%. The evaluation of apoptosis with flow cytometry showed that at 24hours, exposure to PE 10, 100, and 1000µg/mL induces early apoptosis in 19.42%-25.54%, while late apoptosis was only significant P <0.05 in cells challenged with 100µg/mL PE. At 48hours, NHLF exposed to PE 10, 100, and 1000µg/mL showed decreasing early apoptosis: 28.69-32.16%, 12.59-18.84%, and 10.91-12.61%, respectively. The rest of the NHLF exposed to PE showed late apoptosis: 12.03-16-42%, 11.04-15.94%, and 49.23-51.28%. Statistical analysis showed a significance P <0.05 compared to the control. The organic synthesis route of PE allows obtaining rac-1,2-O-Dipalmitoyl-glycero-3-phosphoethanolamine (1), which showed an apoptotic effect on NHLF.