Novel compounds and compositions containing (R)-3-hydroxybutyrate derivatives are disclosed. The compounds and compositions can be used as nutritional supplements to increase physical performance and as therapeutics to ameliorate symptoms of medical conditions, particularly neurological conditions, such as Alzheimer's and similar conditions. Novel methods for making R-3-hydroxybutyrate derivatives also are disclosed. Exemplary methods employ a supercritical solvent, such as supercritical carbon dioxide, and employ a lipase catalyzed esterification or transesterification reaction to produce the (R)-3-hydroxybutyrate derivatives.