An accelerated, improved synthetic route for the preparation of polyether-based dendritic fragments

An accelerated, improved synthetic strategy for the rapid construction of two different series of polyether-based dendritic fragments is described. Several modifications to;the original method for the preparation of these dendritic fragments are detailed. A new branching agent, 5-(3-hydroxypropyloxy)1,3-resorcinol 4, instead of 5-benzyloxy-1,3-resorcinol 2, is employed in this new synthetic protocol. As a result, the number of synthetic operations in each of the iterative cycle is reduced from three to two, as compared to the original procedure. Each iterative synthetic cycle involves two reactions: a bis-O-alkylation reaction of the brancher 4 with a dendritic bromide [Gn]-O(CH2)(3)Br to give a dendritic alcohol of the next generation [G(n+1)]-O(CH2)(3)OH; followed by a functional group conversion of the dendritic alcohol into the corresponding dendritic bromide [G(n+1)]-O(CH2)(3)Br of the same generation. The reaction yields of each iterative cycle are consistently higher than those of the previously reported three step cycle. Using this new protcol, the preparation of a 5th generation dendritic alcohol 15a could be realized in 10 steps and 23% overall yields from 1,3-dibromopropane. (C) 1998 Elsevier Science Ltd. All rights reserved.