Since its discovery, the Julia–Kocienski olefination reaction has over past 30 years become one of the key C-C connective methods that is used in late-stage natural product synthesis. The reaction proceeds under mild reaction conditions, with a wide substrate scope and functional group tolerance range and with high (E) selectivity. In this focused review, we discuss the reaction from a mechanistic point of view and disclose key features that play an important role in reaction selectivity. Finally, the mechanistic aspects of the newly developed modification of the Julia–Kocienski reaction, which allows the formation of both (E) and (Z) olefins from the same reaction partners, are discussed.

Nitro-fatty acids (NO₂FAs) are endogenously produced electrophiles and NRF2 activators with therapeutic potential. We developed a synthetic protocol combining a Henry reaction and base-promoted β-elimination, yielding ultrapure regio/stereoisomers of nitro-stearic (NO₂SA), nitro-oleic (NO₂OA), and conjugated/bis-allylic nitro-linoleic (NO₂LA) acids. These were tested for NRF2 pathway activation in bone marrow cells under different oxygen conditions. We observed that 9- and 10-NO₂OA, and 10-NO₂LA increased NRF2 stabilization under hypoxia, while 9- and 10-NO₂OA significantly upregulated Hmox1 and Gclm at all oxygen levels. 9- and 10-NO₂OA enhanced HO-1 and GCLM proteins independently of oxygen, while 10-NO₂LA was oxygen-dependent, boosting HO-1 under hypoxia and GCLM under ambient conditions. Moreover, 10-NO₂OA and 10-NO₂LA induced NRF2 nuclear translocation. In contrast, the saturated 10-NO₂SA, which has lower electron-acceptor ability, was inactive. In summary, these findings suggest the biological activity of NO₂FAs is dependent on oxygen level, which could be used in future research of other oxidative stress-dependent pathways.

Increasing molecular three-dimensionality is a key strategy in drug discovery, yet α-heteroaryl α,α-disubstituted amino acids (HAAs) remain largely unexplored despite their potential to modulate peptide conformation and recognition. Here we report a stereodivergent Truce-Smiles rearrangement that converts enantioenriched heteroaryl sulfonamides into HAA derivatives with predictable control over configuration at Cα. The method exploits memory-of-chirality and cation-dependent conformational bias to deliver either inversion or retention of configuration under complementary conditions (Method A: NaHMDS/18-crown-6/LiCl; Method B: KHMDS/Cu(I)OTf). Both protocols operate under mild conditions (THF, −78 °C) and accommodate diverse heteroaryl motifs, N-substituents, and amino acid backbones, achieving high enantiomeric ratios and good yields. Downstream functionalization demonstrates compatibility with peptide coupling and reveals intrinsic limitations such as decarboxylation of free acids. This stereodivergent approach expands the toolbox for constructing quaternary stereocenters adjacent to nitrogen and provides practical access to conformationally defined scaffolds for peptide engineering and 3D chemical-space exploration.

The Julia-Kocienski olefination reaction has become over past 30 years since its discovery one of the key C-C connective methods that is used in the late-stage natural product synthesis. The reaction proceeds under mild reaction conditions, with wide substrate scope and functional group tolerance, and with high (E) selectivity. In this review, we discuss the reaction from a mechanistic point of view and disclose key features that play an important role in reaction selectivity. Finally, the mechanistic aspects of the newly developed modification of the Julia-Kocienski reaction, which allows the formation of both (E) and (Z) olefins, from the same reaction partners, are discussed.

Acute radiation syndrome remains a major consequence of high-dose ionizing radiation exposure, and effective pharmacological countermeasures are limited. Nitro-fatty acids possess anti-inflammatory and cytoprotective properties, suggesting potential effectiveness in radiation injury. Here, we investigated the radioprotective effects of 10-nitro-oleic acid (10-NO₂OA) in mouse models of total body irradiation (TBI). C57BL/6 mice were exposed to either sublethal (4 Gy) or LD ₅₀ -level (7.5 Gy) gamma irradiation and treated with 10-NO₂OA according to pre-irradiation, post-irradiation, or combined treatment regimens. Survival, hematological responses, bone marrow cells (BMCs)/colony-forming units (CFU), plasma granulocyte colony-stimulating factor (G-CSF), NRF2-responsive signaling, and intestinal responses were evaluated. Administration of 10-NO₂OA before and after irradiation significantly improved 30-day survival following 7.5 Gy TBI (57% vs. 20% in vehicle-treated controls). In contrast, post-irradiation treatment alone was ineffective, whereas pre-irradiation treatment alone produced a non-significant trend toward improved survival. The protective effect was absent in BALB/c mice, indicating strain dependence. Although 10-NO₂OA did not prevent long-term radiation-induced cytopenia, it increased neutrophil and platelet counts, elevated plasma G-CSF levels shortly after irradiation, and transiently enhanced BMC counts. In irradiated BMCs, 10-NO₂OA activated NRF2-responsive gene expression in vitro and in vivo . Exploratory intestinal analyses revealed improved macroscopic appearance and partial restoration of irradiation-suppressed cytokine and growth factor production. In conclusion, 10-NO₂OA improves survival following LD ₅₀ -level gamma irradiation and is associated with modulation of hematopoietic, cytoprotective, and intestinal responses. These findings identify 10-NO₂OA as a promising candidate radioprotective agent and support a multifactorial mechanism of action.