[Life Science Research Using Small Membered Cyclic Unsaturated Compounds]

Small-membered unsaturated molecules possess unique molecular strain, electronic structures, and photochemical properties, making them attractive platforms for the development of functional molecules in life science research. This review summarizes our efforts to exploit cyclopropenones, cyclobutenediones, and deltic guanidines as photoreactive molecules and bioactive molecular scaffolds. Cyclopropenones can generate highly reactive alkynes upon photoirradiation, enabling light-controlled reactions such as carboxy group modification through photogenerated ynamines and amino group modification through ketene intermediates. Photocatalytic activation further allows these transformations to proceed under longer-wavelength light irradiation and may provide a basis for proximity-dependent labeling strategies. Aminocyclobutenediones were also developed as photoreactive molecules that generate bisketene intermediates and enable selective modification of acidic functional groups in aqueous media. These reactions allowed the introduction of carboxylate, phosphate, and sulfate groups under light-controlled conditions. In addition to their utility as photoreactive molecules, small-membered unsaturated scaffolds were explored as bioactive molecular frameworks. Deltic guanidines were synthesized as highly basic guanidine bioisosteres and shown to exhibit guanidine-like properties in cell permeability and integrin-targeting ligands. Aminocyclopropenones were also identified as a new class of anticancer molecules that suppress cancer cell growth by inhibiting BRD4 function. These studies demonstrate the broad potential of small-membered unsaturated molecules in chemical biology, molecular imaging, and drug discovery.