An asymmetric reaction of chiral imines with a-silyloxy ketene acetals mediated by chiral boron reagents is described. The key to its success is the use of the chiral boron complex prepared in situ from (R)or (S')binaphthol and B(OPh)g. Both diastereomers of a-hydroxy-P-amino ester units are successfully prepared with high selectivities by the chiral boron reagents depending on the geometry of the silyl ketene acetals. The optically pure anti a-hydtoxy-&amino ester is obtained from Q-silyl ketene acetal, while the corresponding syn a-hydroxy-B-amino ester is obtained from (z)-silyl ketene acetal. The method can be efficiently applied to the stereoselective synthesis of tax01 C-13 side chain and the norstatine family.
Some medicinally important compounds involve optically active a-hydroxy-&unino ester units as their key components: taxol, for example, a complex diterpene, is currently considered the most exciting substance in cancer chemotherapy.1 Tax01 possesses high cytotoxicity and strong antitumor activity against cancers which have not responded well to treatment by existing antitumor drugs. It should be noted that the C-13 side chain, N-benzoyl-(2R,3S)-3-phenylisoserine moiety, is essential for the potent antitumor activity.* Accordingly, investigation of the structure-activity relationship for the taxol side chain analogs with some modification appears quite promising to find more effective pharmacological properties. Another example, renin, an asparatic protease, generates angiotensin I from angiotensinogen, and a large number of inhibitory peptides of Taxol KRI 1314 2785 2786 K. HA~T~RI and H. YAMAMOTO human renin have been studied for their potential as agents of antihypertensive therapy.3 KRI-1314, which is one of the renin inhibitors developed for its promise of antihypertensive activity with oral efficacy, bears isopropyl (2R,3S)-3-amino-4-cyclohexyl-2-hydroxybutyrate, cyclohexylnorststine, at its active site.4
Optically active a-hydroxy-P-amino ester, therefore, is essential to promote the activity, making development of a general method for this unit extremely important to further research in the therapeutic area.