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The basic design features associated with the construction of chiral propionate enolates will be presented. It has been found that amide and imide enolates derived from -amino alcohols exhibit excellent levels of asymmetric induction in both alkylations and aldol condensations. For the aldol condensations metal structure was found to be of critical importance in the control of both threo-diastereoselection and chirality transfer. Both boron and zirconium enolates were found to be excellent substrates for the aldol process where >98% enantioselection was observed.

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1 Both the 5-HT 1D and 5-HT 1B receptors are implicated in migraine pathophysiology. Recently isochromans have been discovered to bind primate 5-HT 1D receptors with much higher a nity than 5-HT 1B receptors. In the guinea-pig, a primary animal model for anti-migraine drug testing, however, isochromans bound the 5-HT 1D receptor with lower a nity than the gorilla receptor. 2 This species-speci®c pharmacology was investigated, using site-directed mutagenesis on cloned guinea-pig receptors heterologously expressed in human embryonic kidney 293 cells. Mutations of threonine 100 and arginine 102 at the extracellular side of transmembrane II of the guinea-pig 5-HT 1D receptor to the corresponding primate residues, isoleucine and histidine, respectively, enhanced its a nity for isochromans to that of the gorilla receptor, with little e ects on its a nities for serotonin, sumatriptan and metergoline. Free energy change from the R102H mutation was about twice as much as that from the T100I mutation. 3 For G protein-coupling, serotonin marginally enhanced GTPg 35 S binding in membranes expressing the guinea-pig 5-HT 1D receptor and its mutants, but robustly in membranes expressing the gorilla receptor. Sumatriptan enhanced GTPg 35 S binding in the latter nearly as much as serotonin, and several isochromans by 30 ± 60% of serotonin. 4 We discovered key di erences in the function and binding properties of guinea-pig and gorilla 5-HT 1D receptors, and identi®ed contributions of I100 and H102 of primate 5-HT 1D receptors to isochroman binding. Among common experimental animals, only the rabbit shares I100 and H102 with primates, and could be useful for studying isochroman actions in vivo.