Ester cleavage by S,S-(+)-tetrandrine derivative bearing thiol groups

A chiral cyclophane-type macrocycle bearing two thiol groups has been prepared by chemical modification of S,S-(+)-tetrandrine. Cleavage of p-nitrophenyl acetate by deprotonated form of this macrocycle proceeds with a rate constant expected for a simple thiol anion of similar basicity, but the reactivity toward p-nitrophenyl esters of N-protected amino acids is one order of magnitude higher than expected. This increased reactivity is attributed to a pre-association of voluminous hydrophobic amino acid substrates with a dimeric form of the macrocycle, which shows a small enantioselectivity in favor of L-amino acid ester (k_D/k_L=0.8). Ester cleavage by the monomeric form of the macrocycle proceeds slower, but shows higher and inverted enantioselectivity (k_D/k_L=3.4).