We report here a synthesis of gem-difluorocyclopropanes via a copper-catalyzed C(sp³)–H addition of dioxolane to difluorocyclopropenes. The combinational use of silane and dibenzoyl peroxide was crucial for promoting the reaction, enabling access to gem-difluorocyclopropanes with an acetal moiety in a cis configuration.

We designed and synthesized an oligonucleotide acetylating reagent (Ac-probe) that selectively acetylates the 2′-OH groups of RNA upon forming a duplex with the target RNA. The Ac-probe can be readily prepared via a post-synthetic modification method using an oligodeoxynucleotide probe containing 4-thio-dT. During the acetylation reaction, 4-thio-dT is regenerated as the reaction proceeds. Notably, an efficient modification was observed when the complementary base of RNA to 4-thio-dT was cytosine or uracil, indicating the selectivity for the pyrimidine base.

Site-selective conjugation on aryl azides is hampered by a fundamental trade-off: electron-withdrawing groups that promote the reaction often preclude further functionalization, while versatile electron-donating groups suppress reactivity. We report a strategy that resolves this by using an ortho-amido group to activate an electron-rich aryl azide via an intramolecular hydrogen bond. This non-covalent interaction renders the ortho-amidoaryl azide significantly more reactive than its para-isomer and even activated alkyl azides, although competition experiments revealed that steric hindrance presents a counteracting effect. The principle was successfully applied to achieve excellent site-selectivity in a diazide molecule, favoring reaction at the aryl position. Its utility was further demonstrated in a highly selective classical Staudinger–Bertozzi ligation. This work establishes the ortho-amido group as a powerful controlling element, offering a new click conjugation platform that enables ready functionalization.

Immunoglobulin G (IgG)-binding peptides have been widely used in medicinal chemistry, particularly in the preparation of homogeneous antibody–drug conjugates (ADCs). The dissociation constant (K_d) and kinetic parameters (k_on and k_off) are critical determinants of peptide performance in such applications. In this study, we conducted a structure–activity relationship (SAR) analysis of the IgG-binding peptide 15-IgBP, focusing on Asp3, Tyr6, and Thr15, to identify more potent derivatives with favorable binding affinities and kinetic profiles. Peptides with appropriately tuned ionic structures exhibited rapid binding and release properties, whereas hydrophobic substitutions in solvent-exposed regions led to slower dissociation. By integrating these SAR findings, we identified the optimized affinity peptides, IAPG-2 and IAPG-3, with sub-nanomolar binding affinities (K_d = 0.753 and 0.705 nM, respectively).

Ultra performance liquid chromatography (UPLC)-high resolution (HR)MS/MS and feature-based molecular networking analysis were performed for the extract of a fungus, Arachnomyces bostrychodes, obtained from a cold seep chemosynthetic ecosystem, revealing the presence of new peptides. LC-MS-guided purification afforded three new cyclic tetrapeptides (3–5) containing two N-methyl-l-leucine residues. During the isolation procedure, a new benzophenone (1) and MDN-0093 (2) were isolated. Compounds 4 and 5 exhibited cytotoxicity against HeLa cells with IC₅₀ values of 3.1 and 5.8 μM, respectively.