The 3-azabicyclo[3.1.0]hexan-2-one motif has emerged as a promising scaffold in medicinal and agrochemical research, where it is increasingly incorporated into bioactive compounds. Synthetic approaches to this scaffold rely on oxidation of preformed bicyclic amines or cyclopropanation reactions using diazo-derived carbene precursors. Consequently, the development of diazo-free, redox-neutral strategies for its synthesis remains highly desirable. Among these, strain-release activation of bicyclo[1.1.0]butanes provides an atom-economical platform for generating metal carbenes, enabling diverse bond-forming transformations without the need for diazo compounds.Herein, we report a phosphine ligand-enabled rhodium(I)-catalyzed rearrangement of bicyclo[1.1.0]butane carboxamides that provides a complementary approach to the synthesis of 3-azabicyclo[3.1.0]hexan-2-one derivatives. A series of N-aryl-, N-benzyl-, and N-alkyl-substituted products was synthesized. A plausible mechanistic pathway involving a rhodium carbenoid intermediate is proposed. In addition, the synthesized bicyclic lactams were evaluated for their effects on the viability of MOLT-4T-lymphoblast cells, providing a preliminary assessment of the biological potential of this scaffold.
A visible-light-driven acceptorless dehydrogenative cycloaddition of N-benzylanilines with electron-deficient olefins is described. The reaction proceeds under oxidant-free conditions using an iridium-based photoredox catalyst in combination with a Brønsted acid, affording 1,2,3,4-tetrahydroquinoline derivatives in moderate to good yields. Mechanistic investigations reveal that the conjugate acid of aniline (anilinium) serves as a key single-electron acceptor for the oxidative regeneration of the photocatalyst, thereby enabling catalytic dehydrogenation accompanied by molecular hydrogen evolution. Moreover, the present protocol allows the one-pot synthesis of 2-arylquinolines through a sequential cycloaddition, dehydrogenation, and desulfonylation process under strongly oxidizing photoredox conditions. This study establishes anilinium species as efficient redox partners in photoinduced acceptorless dehydrogenative transformations and expands the synthetic utility of aniline-derived α-aminoalkyl radicals for heterocycle construction.
Multiple-substituted chiral cyclopentanes are ubiquitous in many bioactive molecules. Among the possible strategies, the enantioselective desymmetrization of readily available prochiral cyclopentenes or cyclopentanes constitutes one of the most efficient pathways to access the chiral cyclopentanes bearing multiple stereocenters. This review covers the key advancements published between 2020 and 2026, systematically summarizing the recent progress in cyclopentene/cyclopentane desymmetrization using transition metal catalysis. It highlights the strategies and mechanisms by which different catalytic systems control regio-, diastereo-, and enantioselectivity, with particular attention to the construction of non-adjacent stereocenters and complex bridged ring frameworks. The potential applications of these methodologies in the synthesis of pharmaceutical agents and natural products are also discussed.
Four new aplysinopsin-derived alkaloids (1-4) and one new dolabellane diterpene (5) were isolated from the marine sponge Aplysinopsis sp. Their structures were elucidated by high-resolution mass spectrometry (HRMS), 1D/2D nuclear magnetic resonance (NMR), and electronic circular dichroism (ECD) calculations. Compound (+)-1 exhibited significant anti-inflammatory activity by inhibiting cytokine IL-6 and TNF-alpha expression (IC50 = 6.25 and 7.72 mu M, respectively) while the racemic mixture 2 shown modest inhibitory activity on IL-6 expression with IC50 of 10.08 mu M in LPS-induced THP-1 cells. The in vivo data showed that compound 3 remarkably inhibited the macrophages migration surrounding the neural mound region at concentrations of 20 mu M in CuSO4-treated zebrafish model. These findings highlight Aplysinopsis sp. as rich source of aplysinopsinderived alkaloids with potential anti-inflammatory applications.
