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 des cribed. Several modifications to;the original method for the preparati on of these dendritic fragments are detailed. A new branching agent, 5 -(3-hydroxypropyloxy)1,3-resorcinol 4, instead of 5-benzyloxy-1,3-reso rcinol 2, is employed in this new synthetic protocol. As a result, the number of synthetic operations in each of the iterative cycle is redu ced from three to two, as compared to the original procedure. Each ite rative synthetic cycle involves two reactions: a bis-O-alkylation reac tion of the brancher 4 with a dendritic bromide [Gn]-O(CH2)(3)Br to gi ve a dendritic alcohol of the next generation [G(n+1)]-O(CH2)(3)OH; fo llowed by a functional group conversion of the dendritic alcohol into the corresponding dendritic bromide [G(n+1)]-O(CH2)(3)Br of the same g eneration. The reaction yields of each iterative cycle are consistentl y higher than those of the previously reported three step cycle. Using this new protcol, the preparation of a 5th generation dendritic alcoh ol 15a could be realized in 10 steps and 23% overall yields from 1,3-d ibromopropane. (C) 1998 Elsevier Science Ltd. All rights reserved.