Yunmi Lee

Phytosphingosine, a naturally occurring long-chain fatty alcohol present in the upper layers of the skin, is a key building block for ceramides essential to skin structure. In this study, three phytosphingosine derivatives, (2S,3S,4R)-3,4-dihydroxy-1-(phosphonooxy)octadecan-2-aminium chloride (I), (4S,5S)-2-hydroxy-4-((R)-1-hydroxypentadecyl)-1,3,2-dioxaphosphinan-5-aminium 2-oxide chloride (II), and (2S,3R)-3-hydroxy-1-(phosphonooxy)octadecan-2-aminium chloride (III), were synthesized to evaluate their potential as fungicides. Phytosphingosine-1-phosphate salt I was prepared via a novel four-step phosphorylation process using dimethyl chlorophosphate. O-Cyclic phytosphingosine-1-phosphate salt II was obtained by cyclizing Boc-protected phytosphingosine with POCl₃, while Boc-protected sphinganine was phosphorylated under mild conditions using dimethyl chlorophosphate to yield sphinganine-1-phosphate salt III. The antifungal activities of compounds I–III were assessed in vitro against four phytopathogenic fungi: Botrytis cinerea, Fusarium asiaticum, Fusarium solani, and Rhizoctonia solani. Among these, compound II exhibited the most potent growth inhibitory activity against Fusarium asiaticum (IC₅₀ = 27.5 μg/mL). In vivo evaluations using infected apples further confirmed the concentration-dependent inhibitory activity of compound II against F. asiaticum (IC₅₀ = 108 μg/mL). Morphological analyses revealed shortened hyphal structures and abnormal branching in F. asiaticum, while compound II treatment was associated with a concentration-dependent shift toward predominantly yeast-form morphology in adherent Candida albicans populations. In silico docking against five selected fungal enzymes suggested a potential interaction between compound II and N-myristoyltransferase (NMT), characterized by predicted hydrophobic interactions within the acyl-chain binding pocket and a possible hydrogen bond involving LEU171. Molecular dynamics simulations further supported the relative stability of the predicted NMT–compound II complex. Together, these findings highlight the O-cyclic phytosphingosine-1-phosphate salt II as a promising antifungal candidate and suggest NMT as a potential molecular target warranting further experimental validation.

Nitrogen-containing aromatic amines and aza-heterocycles are ubiquitous motifs in pharmaceuticals and functional materials, making efficient C–N bond formation a fundamental transformation in synthetic chemistry. The direct hydroamination of alkenes using (hetero)aromatic N–H nucleophiles offers an atom- and step-economical strategy; however, the reduced nucleophilicity and distinct coordination behavior of these substrates render such transformations inherently challenging. Recently, copper catalysis has emerged as a versatile and practical platform for addressing these limitations. Owing to its redox flexibility and ligand tunability, copper facilitates multiple activation modes, including copper–amido-mediated nucleophilic addition or aminocupration, Lewis acid-type alkene activation, and radical-mediated pathways. These complementary mechanisms provide access to diverse alkene classes with control over regioselectivity (Markovnikov vs anti-Markovnikov addition), stereoselectivity, and functional group tolerance. This review summarizes recent advances in the copper-catalyzed hydroamination of alkenes with (hetero)aromatic N–H nucleophiles, emphasizing the mechanistic paradigms and the factors governing selectivity.

We report a ligand-controlled, regiodivergent Cu/Pd-catalyzed hydroarylation of unactivated allenes. The reaction proceeds via Cu-catalyzed hydroalumination with DIBAL-H and subsequent additive-free Pd-catalyzed cross-coupling with aryl bromides. The key feature of this work is the discovery that modulation of the palladium ligand decisively enables complete regiodivergence. Bulky monodentate Xphos ligands promote exclusive γ-selective arylation, while bidentate Josiphos-type ligands switch the pathway to afford α-selective arylation. The method features mild conditions, scalability, and broad utility for synthesizing polysubstituted aromatic compounds.

This study introduces a highly selective hydrocyanation method based on copper-catalyzed hydroalumination of allenes with diisobutylaluminum hydride, followed by the regio- and stereoselective allylation with p-toluenesulfonyl cyanide. The proposed methodology is efficient for accessing acyclic β,γ-unsaturated nitriles with α-all-carbon quaternary centers and achieves yields up to 99% and excellent regio- and E-selectivity. The reaction proceeds under mild conditions and shows broad applicability to di- and trisubstituted allenes. Its practicality is demonstrated through the gram-scale synthesis and functional group transformations of amines, amides, and lactams, emphasizing its versatility and synthetic significance.

The formal hydroamidation of alkyne is a powerful synthetic method that enables the formation of various α,β‐unsaturated amides. In this article, the efficient formal hydroamidation of terminal and internal alkynes is described, which constitutes the Ni‐catalyzed α‐selective hydroalumination of alkynes and subsequent treatment with isocyanates. This method is gram‐scalable and the synthetic utility is highlighted by the synthesis of a β‐lactam from α‐phenyl acrylamide.

A copper-catalyzed hydrodechlorination of primary, secondary, and tertiary alkyl chlorides using diisobutylaluminum hydride is reported. This catalytic system offers a broad substrate scope, high yields, and good functional group tolerance. Mechanistic investigations indicated that the reaction predominantly proceeds via a radical pathway, as supported by radical clock experiments. Importantly, this study provides a new approach for the selective hydrodechlorination of unactivated alkyl chlorides and expands the utility of Cu-hydride catalysis in sustainable chemical synthesis.

A straightforward and highly selective hydroamidation process involving the copper-catalyzed hydroalumination of allenes, followed by allylation with isocyanates, is presented. This methodology offers a direct and efficient route to the construction of challenging α-all-carbon quaternary centers within β,γ-unsaturated acyclic amides, providing high yields (up to 99%) with excellent regio- and E-stereoselectivities. The reaction operates under mild and simple conditions and accommodates a wide range of readily accessible di- or tri-substituted allenes and isocyanates. To demonstrate the practicality of this approach, we conduct a gram-scale reaction to produce the desired α-quaternary amide and showcase its versatility by synthesizing six- and seven-membered lactams. These results highlight the synthetic value of this methodology.

A copper-catalyzed chemo- and stereoselective method for the synthesis of (E)-2-silyl-1,3-butadienes from a broad range of allenols using mild Si-B reagents is reported in this study. Our protocol required a short reaction time at ambient temperature to produce the desired dienes in high yields. Synthetic applications are highlighted by the one-pot synthesis of tetrasubstituted arylsilanes from allenols as well as the further functionalization of C-Si bonds.