Preparation of hexaaza and heptaaza macrocycles functionalized with a single aminoalkyl pendant arm.
A practical and reproducible route for the preparation of 1,4,7,10,13,16,19-heptaazacyclohenicosane (1), 1,4,7,10,13,16-hexaazacyclooctadecane (2), and 1,4,7,10,13,17-hexaazacycloicosane (3) bearing a single N-(2-aminoethyl) pendant arm has been developed. Richman-Atkins cyclization in the presence of caesium carbonate was applied to construct the macrocycle from 3-benzoyl-N1,N5-ditosyl-3-azapentane-1.5-diamine and the appropriate fully N-tosylated N alpha, N omega-bis(2-mesyloxyethyl) tri- or tetra-amine. The benzoyl group was selectively removed with potassium tert-butoxide, and the exposed nitrogen atom was reacted with N-tosylaziridine. The tosyl protections were removed with hydrogen bromide in acetic acid, and the product was converted to a free base with the aid of a strong anion exchange resin (OH- form).
Zhang
Zhibo
Z
Department of Chemistry, University of Turku, FIN-20014, Turku, Finland.
Mikkola
Satu
S
Lönnberg
Harri
H