MDL 28,726 is a key intermediate in the synthesis of the ACE inhibitors MDL
27,210A and MDL 100,240, An efficient nine-step synthesis of this tricycli
c acid, which has three chiral centers, was developed beginning with 3,4-di
hydro-2H-pyran. A key step in the synthesis features an enzyme-catalyzed re
solution of the lithium salt of the N-trifluoroacetamide of (R,S)-6-hydroxy
norleucine. All of the steps were optimized and completed in reactor equipm
ent using environmentally acceptable processes. Process development of this
route is described.