Silica gel

All reagents were purchased from Sigma-Aldrich and used without further purification. Dichloromethane (DCM) and tetrahydrofuran (THF) were distilled from calcium hydride. All reactions were conducted in flame-dried glassware and under nitrogen atmosphere unless stated otherwise. All reactions were magnetically stirred and monitored by thin-layer chromatography (TLC) using Merck silica gel 60 F₂₅₄ pre-coated plates (0.25 mm). Flash column chromatography was performed using silica gel (0.032–0.063 mm particle size) from Fisher Scientific. All ¹H-, ¹³C- and 2D-NMR experiments were performed on either a Bruker Avance DPX 400 MHz, Bruker Avance III HD NanoBay 400 MHz or DRX600 NMR spectrometer equipped with a TXI (5 mm) cryoprobe. Chemical shifts were reported in ppm using residual CDCl₃ (δ_H; 7.26 ppm, δ_C; 77.36 ppm), or (CD₃)₂CO (δ_H; 2.05 ppm, δ_C; 29.84 ppm), or CD₃OD (δ_H; 3.31 ppm, δ_C; 49.00 ppm) as an internal reference. Polarimetry data was collected on a JASCO polarimeter (model no. P-1010). LC–MS was conducted using an Agilent 6130 single-quadrupole LC–MS system. High-resolution mass-spectrometry (HRMS) was conducted using a Thermo-Fisher QExactive-Plus Orbitrap instrument. Infrared spectroscopy was conducted using a Thermo-Fisher Nicolet iS5 FT–IR spectrometer.

A Bruker DRX 400 or 500 MHz spectrometer (Bruker-Biospin, Karlsruhe, Germany) was used for the analysis of NMR signals using methanol-d₄ as a solvent. The UV and IR spectra were obtained using Jasco UV-550 (JASCO, Tokyo, Japan) and Perkin–Elmer model LE599 (Perkin–Elmer, Waltham, MA, USA) spectrometers, respectively. ESIMS and HRESI-TOF-MS data were obtained with LCQ Fleet and maXis 4G mass spectrometers (Bruker Daltonics, Bremen, Germany), respectively. Semi-preparative HPLC (Waters, Milford, MA, USA) was performed using a Waters 515 HPLC pump with a 996-photodiode array detector, and Waters Empower software using a Gemini-NX ODS-column (150 × 10.0 mm and 150 × 21.2 mm). Column chromatography procedures were performed using silica gel (200–400 mesh, Fisher Scientific, Waltham, MA, USA) and Sephadex LH-20 (25–100 µm, Pharmacia Fine Chemical Industries Co., Uppsala, Sweden). Thin-layer chromatography (TLC) was performed using aluminum plates precoated with Kieselgel 60 F₂₅₄ (0.25 mm, Merck, Darmstadt, Germany).

Adult bioassays were conducted following the protocol of WHO for Aedes mosquitoes [58 ]. For the Kano population the insecticides were pyrethroids: 0.25% and 0.75% permethrin, 0.03% and 0.05% of deltamethrin, ƛ-cyhalothrin, and α-cypermethrin, and 0.15% cyfluthrin; organochlorides: 4% of DDT and dieldrin; organophosphate: 1% fenitrothion; and carbamate: 0.1% propoxur. Minimum of four replicates each of 25 Aedes aegypti females (3–5 day old) were exposed for 1 h. Mosquitoes were transferred to holding tubes and fed with sugar for 24 h before mortalities were recorded, and dead females stored in silica gel (Fisher Scientific, Loughborough, UK). For control, during each experiment, two replicates of 20–25 females from the same populations, and of the same age were kept in holding tubes without insecticide exposure. For the Pantami collection of 2020 only 4% DDT was tested.