C(sp³)–C(sp³) Radical-Cross-Coupling Reaction via Photoexcitation

The photoexcitation of 4-alkyl-1,4-dihydropyridines (alkyl-DHPs) in the presence of a base triggers the single-electron-transfer-mediated desulfonative radical-cross-coupling (RCC) reaction without the need for any metal or photocatalyst. 4-Alkyl-substituted 1,4-DHPs as the electron donor (reductant) and alkyl sulfones as the electron acceptor (oxidant) are chosen strategically as the two best-matched modular radical precursors for the construction of C(sp3)–C(sp3) bonds. Ultraviolet light-emitting diodes (365 nm) have proven to be adequate for inducing single-electron transfer between two radical precursors in the excited state. Following this designed strategy, a diverse collection of primary, secondary, and tertiary persistent alkyl radicals from both radical precursors have been used to forge C(sp3)–C(sp3) bonds. This blueprint features good functional group compatibility, a broad scope, and detailed mechanistic investigation

C(sp³)–C(sp³) Radical-Cross-Coupling Reaction via Photoexcitation

The photoexcitation of 4-alkyl-1,4-dihydropyridines (alkyl-DHPs) in the presence of a base triggers the single-electron-transfer-mediated desulfonative radical-cross-coupling (RCC) reaction without the need for any metal or photocatalyst. 4-Alkyl-substituted 1,4-DHPs as the electron donor (reductant) and alkyl sulfones as the electron acceptor (oxidant) are chosen strategically as the two best-matched modular radical precursors for the construction of C(sp3)–C(sp3) bonds. Ultraviolet light-emitting diodes (365 nm) have proven to be adequate for inducing single-electron transfer between two radical precursors in the excited state. Following this designed strategy, a diverse collection of primary, secondary, and tertiary persistent alkyl radicals from both radical precursors have been used to forge C(sp3)–C(sp3) bonds. This blueprint features good functional group compatibility, a broad scope, and detailed mechanistic investigation

Crystal or Low Molecular Mass Organogel Based on Sugar-Derived Chiral Pyrano[2,3-<i>b</i>]naphtho[1,2-<i>e</i>]pyrans

2-C-Acetoxymethyl glycal derivatives reacted with β-naphthol in the presence of InCl3 (30 mol %) to give chiral pyrano[2,3-b]naphtho[1,2-e]pyrans in good to excellent yields via stereoselective Ferrier rearrangement−tandem cyclization. The major glucose-derived product exhibited crystal packing with C−H···O and C−H···π (arene) interactions and the major galactose-derived product, a low molecular mass organogelator (LMOG), formed a rare type of micro tubular gel assembly in n-hexane

Crystal or Low Molecular Mass Organogel Based on Sugar-Derived Chiral Pyrano[2,3-<i>b</i>]naphtho[1,2-<i>e</i>]pyrans

2-C-Acetoxymethyl glycal derivatives reacted with β-naphthol in the presence of InCl3 (30 mol %) to give chiral pyrano[2,3-b]naphtho[1,2-e]pyrans in good to excellent yields via stereoselective Ferrier rearrangement−tandem cyclization. The major glucose-derived product exhibited crystal packing with C−H···O and C−H···π (arene) interactions and the major galactose-derived product, a low molecular mass organogelator (LMOG), formed a rare type of micro tubular gel assembly in n-hexane

Exploiting <i>N</i>‑Centered Umpolung Reactivity of α‑Iminomalonates for the Synthesis of <i>N</i>‑Sulfenylimines and Sulfonamides

An efficient and interesting N-centered umpolung method has been disclosed to construct beneficial S–N bonds, furnishing N-sulfenylimines, which can readily be converted into the corresponding sulfonamide derivatives in a one-pot sequential operation. N-Sulfenylimines are potent intermediates in organic synthesis, whereas sulfonamides are of major molecular interest due to their rich biological activities and wide applicability in medicinal chemistry. Owing to the simple reaction conditions and setup, this protocol displays a broad and versatile substrate scope, resulting in excellent functional group tolerability toward the synthesis of both N-sulfenylimines and sulfonamides. A density functional theory (DFT) computed and experimentally supported convenient mechanism has been proposed for this unique method

Exploiting <i>N</i>‑Centered Umpolung Reactivity of α‑Iminomalonates for the Synthesis of <i>N</i>‑Sulfenylimines and Sulfonamides

An efficient and interesting N-centered umpolung method has been disclosed to construct beneficial S–N bonds, furnishing N-sulfenylimines, which can readily be converted into the corresponding sulfonamide derivatives in a one-pot sequential operation. N-Sulfenylimines are potent intermediates in organic synthesis, whereas sulfonamides are of major molecular interest due to their rich biological activities and wide applicability in medicinal chemistry. Owing to the simple reaction conditions and setup, this protocol displays a broad and versatile substrate scope, resulting in excellent functional group tolerability toward the synthesis of both N-sulfenylimines and sulfonamides. A density functional theory (DFT) computed and experimentally supported convenient mechanism has been proposed for this unique method

Presentation_1.PDF

<p>Bacterial pathogens are associated with severe infections (e.g., sepsis) and exacerbation of debilitating conditions such as chronic obstructive pulmonary disease (COPD). The interactions of bacterial pathogens with macrophages, a key component of innate immunity and host defense, are not clearly understood and continue to be intensively studied. Having previously demonstrated a role of Wnt5A signaling in phagocytosis, we proceeded to decipher the connection of Wnt5A signaling with infection by pathogenic bacteria, namely Pseudomonas aeruginosa (PA) and Streptococcus pneumoniae (SP), which are related with the progression of COPD and sepsis. We found that during the initial hours of infection with PA and SP, there is decrease in the steady state levels of the Wnt5A protein in macrophages. Suppression of Wnt5A signaling, moreover, impairs macrophage clearance of the bacterial infection both in vitro and in vivo. Activation of Wnt5A signaling, on the other hand, enhances clearance of the infection. Macrophage-mediated containment of bacterial infection in our study is dependant on Wnt5A-induced Rac1/Disheveled activation and cytochalasin D inhibitable actin assembly, which is associated with ULK1 kinase activity and LC3BII accumulation. Our experimental findings are consistent with Wnt5A signaling-dependent induction of autophagic killing (xenophagy) of PA and SP, as further substantiated by transmission electron microscopy. Overall, our study unveils the prevalence of a Wnt5A—Rac1—Disheveled-mediated actin-associated autophagy circuit as an important component of innate immunity in host macrophages that may turn out crucial for restricting infection by leading bacterial pathogens.</p

DataSheet_1_Wnt5A Signaling Blocks Progression of Experimental Visceral Leishmaniasis.pdf

Visceral leishmaniasis, caused by L. donovani infection is fatal if left untreated. The intrinsic complexity of visceral leishmaniasis complicated further by the increasing emergence of drug resistant L. donovani strains warrants fresh investigations into host defense schemes that counter infections. Accordingly, in a mouse model of experimental visceral leishmaniasis we explored the utility of host Wnt5A in restraining L. donovani infection, using both antimony sensitive and antimony resistant L. donovani strains. We found that Wnt5A heterozygous (Wnt5A +/-) mice are more susceptible to L. donovani infection than their wild type (Wnt5A +/+) counterparts as depicted by the respective Leishman Donovan Units (LDU) enumerated from the liver and spleen harvested from infected mice. Higher LDU in Wnt5A +/- mice correlated with increased plasma gammaglobulin level, incidence of liver granuloma, and disorganization of splenic white pulp. Progression of infection in mice by both antimony sensitive and antimony resistant strains of L. donovani could be prevented by activation of Wnt5A signaling through intravenous administration of rWnt5A prior to L. donovani infection. Wnt5A mediated blockade of L. donovani infection correlated with the preservation of splenic macrophages and activated T cells, and a proinflammatory cytokine bias. Taken together our results indicate that while depletion of Wnt5A promotes susceptibility to visceral leishmaniasis, revamping Wnt5A signaling in the host is able to curb L. donovani infection irrespective of antimony sensitivity or resistance and mitigate the progression of disease.</p

Additional file 1 of COVID-19 vaccination does not affect male sexual functions

Additional file 1