Synthesis of Macrocyclic Hexaoxazole (6OTD) Dimers, Containing Guanidine and Amine Functionalized Side Chains, and an Evaluation of Their Telomeric G4 Stabilizing Properties

Scheme 1

Synthesis of 6OTD dimers. (a) Pd(OH)₂/C, H₂, THF-MeOH; (b) LiOH⋅H₂O, THF-H₂O; (c) DMT-MM, N-methylmorpholine, THF-H₂O, 89% over 2 steps from 4 and 6; (d) Pd(PPh₃)₄, morpholine, DMF-THF 99%; (e) LiOH·H₂O, THF-H₂O; (f) N,N-diisopropylethylamine, DMAP, DPPA, DMF-CH₂Cl₂, 78% over 2 steps from 9; (g) Pd(OH)₂/C, H₂, MeOH; h) N,N-diisopropylethylamine, adipoyl chloride, 28% over 2 steps from 10; (i) TFA, CH₂Cl₂ 98%; (j) Et₃N, HgCl₂, 1,3-bis(tert-butoxycarbonyl)-2-methyl-2-thiopseudourea; (k) TFA, CH₂Cl₂, 42%; Boc = tert-butoxycarbonyl, Cbz = benzyloxycarbonyl, DMT-MM = 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride, DMAP = 4-dimethylaminopyridine, DPPA = diphenylphosphoryl azide, TFA = trifluoroacetic acid.