*3.1. General Experimental Procedures*

NMR spectra were recorded at 25 ◦C on a Bruker AVANCE HDX 800 MHz spectrometer (Fällanden, Zürich, Switzerland) equipped with a TCI cryoprobe. The 1H and 13C NMR chemical shifts were referenced to the solvent peak for CD3OD (δ<sup>H</sup> 3.31 and δ<sup>C</sup> 49.00) and CDCl3 (δ<sup>H</sup> 7.26 and δ<sup>C</sup> 77.16). UV spectra were recorded using a JASCO V-650 UV/vis spectrophotometer (Tokyo, Japan). IR data were acquired using an attached Universal Attenuated Total Reflectance (UATR) Two module on a PerkinElmer spectrophotometer (Waltham, MA, USA). LRESIMS data were recorded on a Thermo Fisher MSQ Plus single quadrupole mass spectrometer (Waltham, MA, USA). HRESIMS data were recorded on a Bruker maXis II ETD ESI-qTOF (Bremen, Germany). A Thermo Scientific Dionex Ultimate 3000 HPLC (Waltham, MA, USA) was used for semi-preparative HPLC separations. An Alltech stainless steel guard cartridge (10 mm × 30 mm) (Sydney, NSW, Australia) was used for loading pre-adsorbed synthetic reaction products onto the semi-preparative HPLC columns. Alltech Davisil NH2-bonded silica (35–75 μm, 150 Å) (Sydney, NSW, Australia) and C18-bonded silica (35–75 μm, 150 Å) (Sydney, NSW, Australia) were used for pre-adsorption work before HPLC separations. TLC was carried out on Merck gel F254s pre-coated NH2 glass plates (Darmstadt, Germany) and was observed using UV light. A YMC NH2-bonded silica column (5 μm, 120 Å, 20 mm × 150 mm) (Kyoto, Japan) and a ThermoElectron Betasil C18-bonded silica column (5 μm, 143 Å, 21.2 × 150 mm) (Waltham, MA, USA) were used for semi-preparative HPLC separations. All solvents used for chromatography, UV and MS were Honeywell Burdick & Jackson HPLC grade (Muskegon, MI, USA), and the H2O was Sartorius arium proVF (Göttingen, Germany) filtered. All synthetic reagents (including papaverine HCl) were purchased from Sigma-Aldrich (St. Louis, MO, USA) and used without further purification. NMR spectra were processed using MestReNova version 11.0 (Santiago de Compostela, Spain).

#### *3.2. Generation of the Papaverine Library (TFA-Free Method): Compounds 2–5, 9, and 11*

Papaverine hydrochloride (**1a**, 37.5 mg, 0.1 mmol) was dissolved in CH2Cl2/H2O or DMSO/H2O (2.5:1, 100 μL:40 μL) before the addition of the sulfinate reagent (85.6–198.9 mg, 0.6 mmol) at room temperature. The mixture was cooled to 0 ◦C before TBHP (40 μL, 0.6 mmol) was slowly added, after which time the stirred mixture slowly warmed to room temperature over 16 h. Crude reaction products were dried under N2 and pre-adsorbed to NH2-bonded silica (≈1 g) overnight with the dry material packed into a stainless steel guard cartridge, which was subsequently attached to a NH2 semi-preparative HPLC column. Isocratic conditions of 100% *n*-hexane for 10 min, followed by a linear gradient to 20% *i*-PrOH/*n*-hexane over 50 min, then isocratic conditions of 20% *i*-PrOH/*n*-hexane for 10 min all at a flow rate of 9 mL/min was used for each HPLC separation. Sixty fractions (60 × 1 min) were collected from the start of the HPLC run. Fractions containing UV-active material from each HPLC run were analyzed using 1H NMR spectroscopy and LCMS, and relevant fractions with a purity >90% were combined to produce the desired products. Compounds **2**–**5** and **11** were synthesized using the CH2Cl2/H2O solvent system, while compound **9** was generated using the DMSO/H2O mixture.
