Synthesis of Several Chiral Atom Transfer Radical Polymerization Initiators and Its Helix-sense-selective Initiating Function for ATRP

Abstract

Five optically active alkyl bromides were synthesized and were used as chiral atom transfer radical polymerization (ATRP) initiators for the helically selective polymerization of 1-phenyldibenzosuberyl methacrylate (PDBSMA). In order to avoid the racemization of the primary free radical formed in initiating step, the optically active alkyl bromide initiators were designed as such a structure in which the bromine atom did not connect to the chiral center. The chiral ATRP initiators tested here are (S)-2,2'-di(bromomethyl)-1,1'-binaphthyl, (S)-2-bromomethyl-2-methyl-1,1'-binaphthyl, menthyl α-bromophenylacetate, N-menthyl α-bromophenylacetamide and (3β,5α)-cholestan-3-yl α-bromo phenylacetate. (S)-2,2'-Di(bromomethyl)-1,1'-binaphthyl, (S)-2-bromomethyl-2-methyl-1,1'-binaphthyl and menthyl α-bromophenylacetate were synthesized following the method reported by literatures. N-menthyl α-bromophenylacetamide was synthesized by adding dropwise the solution of α-bromophenylacetyl chloride in tetrahydrofuran (THF) into the mixture of menthylamine, triethylamine and THF with stirring at room temperature within 3 h and stirring at room temperature for another 8 h after the addition. (3β,5α)-Cholestan-3-yl α-bromo phenylacetate was synthesized using the method for the synthesis of menthyl α-bromophenylacetate except using (3β,5α)-cholestanol instead of menthol. The poly-PDBSMA obtained from the ATRP initiated by the optically active alkyl bromides was fractionated into THF-soluble part and THF-insoluble part. THF-soluble part was optically active. By studying the chiroptical properties of the THF-soluble part of the poly-PDBSMA and by comparing the optical rotation of the THF-soluble part of the poly-PDBSMA with that of the poly(methyl methacrylate) (poly-MMA) obtained under the same polymerization condition, we concluded that the ATRP initiated by the optically active alkyl bromides was helix-sense selective. The NMR study of poly-MMA derived from the THF-insoluble part showed that the polymer produced from the polymerization initiated by (S)-2,2'-di(bromomethyl)-1,1'-binaphthyl was isotactic, which proved further that the ATRP initiated by the optically alkyl bromines was helix-sense selective. Among the five optically active alkyl bromides, (S)-2,2'-di(bromomethyl)-1,1'-binaphthyl and (S)-2-bromomethyl-2-methyl-1,1'-binaphthyl had the best helical selectivity. The helix-sense selectivity depended on the polymerization temperature. The ceiling temperature is 70 ℃. In the range of 0-70 ℃, the helix-sense selectivity increased with the increase of the polymerization temperature.

Synthesis and preliminary biological evaluation of gabactyzine, a benactyzine-GABA mutual prodrug, as an organophosphate antidote

“…To facilitate the acylation step, an alternative approach was undertaken whereby the α-bromophenylacetic acid 10 was converted into the corresponding acyl chloride 11 45 , which subsequently was treated with diethylaminoethanol gave the ester 12 46 . The bromide in compound 12 was then replaced with N-Boc-GABA in the presence of the dehydrohalogenating base DBU, to give 13.…”