The synthesis and in vitro evaluation of a new series of salvinorin A analogues substituted at the C(2) position with natural amino acids is reported. Compound 12, containing Val, displayed high affinity and full agonist activity at the kappa-opioid receptor. Analogues with bulky and/or aromatic residues were inactive, showing the importance of size and electronegativity of C(2)-substituents...
Salvinorin A is the major active ingredient of Salvia divinorum, a plant used by the Mazatec Indians of Mexico for spiritual and medical purposes. Different preparations from S. divinorum are also used in traditional healing practices to treat gastrointestinal disorders, including diarrhea. The recent extensive research on salvinorin A and other neoclerodane diterpenoids derived from S....