Scheme 1.

Synthesis of inhibitors 32 (A) and 52 (B). a) NaHSO3, DMA, reflux/overnight, 65%–80%; b) Ac₂O, pyr., DCM, rt, 2 h, 90%; c) 1-bromo-n-chloro-octane, K₂CO₃, DMF, rt, 12 h, followed by NaN₃, DMF, overnight 60 °C, 80%–90%; d) MOM-Cl, DIPEA, DCM, rt, 12 h; e) K₂CO₃, propargyl bromide, DMF, rt/2 h, 85%–90%; f) 3N HCl, acetone, reflux/overnight, 55%–60%; g) CuSO₄·5H₂O (1 mol %), sodium ascorbate (5 mol %), DMF/H₂O (1:1), rt, overnight, 80%–95%; h) SO₃/Me₃N, TEA, CH₃CN, microwave, 90 °C, 0.5–6 h, 85%–90%; i) K₂CO₃, dibromobutane (0.5 equiv), DMF, rt, 6 h, 85%–90%; j) p-toluenesulfonic acid, MeOH, reflux, 48 h, 55%–65%.