the lowest energy conformation of the macrocycle to design substrate-controlled stereochemical reactions. Neopeltolide Neopeltolide was originally isolated from sponges near the Jamaican coast and exhibits nanomolar cytoxic activity against several lines of cancer cells. The synthesis of the neopeltolide macrocyclic core displays a hydrogenation controlled by the ground state conformation of the macrocycle. Criticisms The peripheral attack model is based on predicting lowest energy conformations of an inherently complicated system, where nuanced perturbations can cause huge stereodifferentiating consequences. By modeling peripheral attack using the Curtin-Hammett scenario depicted above, the transition state is excluded from this conformation analysis by assuming that the barrier to each transition state from a given conformation is the same and thus that ground state conformations are the sole product determining factor. A significant criticism is the mapping of medium-sized ring conformations and influences onto larger ring systems. Macrocycles can possess varying degrees of rigidity in their structure, making a single peripheral attack model difficult to apply to all systems. Different classes of reactions might not fit the peripheral attack model, as reactions such as epoxidations, hydroxylations, alkylations, and reductions all proceed through different transition states. See also Asymmetric induction Conformational isomerism Curtin-Hammett principle Macrocycle Metallaprism References External links http://isites.harvard.edu/fs/docs/icb.topic960737.files/lecture%2015.pdf Macrocycles Organic chemistry Organic reactions