Isolation and Total Syntheses of Cytotoxic Cryptolactones A₁, A₂, B₁, and B₂: α,β-Unsaturated δ‑Lactones from a <i>Cryptomyzus</i> sp. Aphid

The cryptolactones A₁, A₂, B₁, and B₂, which are α,β-unsaturated δ-lactones, were isolated from a <i>Cryptomyzus</i> sp. aphid. The structures were established by 1-D and 2-D NMR spectra and CI-HRMS. Their absolute configurations were determined with the Kusumi–Mosher method, combined with asymmetric total syntheses. The syntheses were accomplished with the Mukaiyama aldol reaction and olefin metathesis, which utilized the second-generation Grubbs catalyst for the key steps. These compounds exhibited cytotoxic activity against human promyelocytic leukemia HL-60 cells with IC₅₀ values of 0.97–5.3 μM