Scheme 4.

Synthesis of 14-membered analogs 4, 5 and 6 via macroetherification.

Key: (a) i. EDCI, HOBT, CH₂Cl₂, RT, 12 h; ii. 0.5 N HCl, 72%; (b) i. K₂CO₃, DMSO (2 mM), 4 Å sieves, 2 h; ii. 1N HCl, 85%; (c) i. CrCl₂, DMF, RT, 12 h; ii. 1 N HCl, 73%; (d) BBr₃, –78 °C, 1 h, 91%; (e) BBr₃ –78 °C, 1h, 58%; (f) i. AcOH/H₂O, 9:1, NaNO₂, 0 °C; ii. NaN₃, 0 °C, 66%