Fig. 1.

Chemical strategies for syntheses of MRS2481 and analogs. (A) Preparation of analogues of variable spacer chain lengths and variable substitution of the pyridinium moiety. For the structure of R₁, refer to Table 1. Reagents: (a) benzyltrimethylammonium hydroxide, tetrabutylammonium iodide at r.t. for 2 days; (b) sodium iodide in acetone; (c) pyridine derivative in acetone at 50 °C for 3 days. (B) Preparation of compound 17, which contains a chemically reactive aryl amino group. Reagents: (a) tin, acetic acid, HCl at 100 °C for 1.5 h; (b) di-t-butyl-dicarbonate in methanol at 45 °C for 1 h; (c) benzyltrimethylammonium hydroxide, tetrabutylammonium iodide at r.t. for 2 days; (d) sodium iodide in acetone; (e) pyridine in acetone at 50 °C for 3 days; (f) trifuoroacetic acid. (C) Preparation of 4-substituted pyridinium salts 19 and 20 and non-pyridinium derivatives, including the symmetric diester 22. Reagents: (a) 1,8-dibromooctane, benzyltrimethylammonium hydroxide, tetrabutylammonium iodide at r.t. for 3 days; (b) N-methylmorpholine, tetrabutylammonium iodide in acetone at 50 °C for 2 days; (c) 4-propyl-pyridine, tetrabutylammonium iodide in acetone at 50 °C for 3 days; (d) 4-(2-hydroxyethyl)-pyridine, tetrabutylammonium iodide in acetone at 50 °C for 3 days.