Synthesis, characterization, and solution properties of 5-ethyl-substituted poly( L -prolines). Synthesis of cis - and trans -5-ethyl- L -proline and optically active poly( cis -5-ethyl- D -proline)

Abstract

This article reports a continuation of our work on the substituent effects on the preferred helical conformations and the mutarotation of substituted poly( L -prolines). The size of the substituent has been increased from a methyl group to an ethyl group in the 5 position. The purpose is twofold: (i) according to our theoretical conformational energy calculations, an ethyl group in the 5 position can exert a greater steric effect than can a methyl group; and (ii) the rotation-isomerization of the ethyl group introduces a new intriguing fact to the problem. The cis isomer of 5-ethylproline was synthesized by catalytic hydrogenation of Δ′-2-ethylpyrroline-5-carboxylic acid, whereas for trans -5-ethylproline, a chemical separation method involving p -toluenesulfonyl chloride was used. The resolution of cis -5-ethylproline and the assignment of absolute configurations have been carried out by fractional crystallization and circular dichroism spectroscopic techniques, respectively. Poly( cis -5-ethyl- D -proline) was obtained from its corresponding N -carboxyanhydrides via a ring opening polymerization.