Two chiral derivatives of a mesitylene-based calixarene known to exist in the 1,3-alternate conformation were prepared by the attachment of homochiral residues to the four exo-hydroxy groups. Thus, the enantiotopic protons of the central scaffold became diastereotopic, leading to a doubling of their 1H NMR signals in one example. From the temperature independence of the NMR spectrum, a lower limit of 24.2 kcal/mol could be estimated for the barrier of ring inversion. MM3 calculations confirm the 1,3-alternate conformation as the energy minimum, and estimate a barrier of 25.7 kcal/mol for the 1,3-alternate-to-1,3-alternate* interconversion process. This high barrier is due to the repulsive steric interactions between exo-methyl groups at vicinal rings when these groups pass each other. Copyright (C) 2000 Elsevier Science Ltd.