Neotame: Synthesis, Stereochemistry and Sweetness

Abstract

Neotame, an alkylated dipeptide consisting of L,L-stereochemistry, is a new high intensity sweetener being developed by the Nutrition and Consumer Products Sector of Monsanto. The three diastereoisomers of neotame, L,D; D,L; and D,D were synthesized and evaluated for sweetness by sensory testing. Only the L,L-isomer was found to be sweet. The three-dimensional structure of the L,L diastereoisomer determined from single-crystal x-ray analysis demonstrates that the compound exists in an “L shaped” conformation, previously proposed for the requirement of the sweetness ability by aspartyl-based dipeptide compounds. The confirmation of neotame in the solid state also demonstrates well-oriented hydrophobic and hydrophilic regions which likely account for the high sweetness intensity of this dipeptide compound.