Regioselective opening of N-Cbz glutamic and aspartic anhydrides with carbon nucleophiles

Navigating around Patented Routes by Preserving Specific Motifs along Computer-Planned Retrosynthetic Pathways

“…Chemoselective reduction of the ester and subsequent Appel reaction (note blue halo indicating the need for protection of carboxylic acid 29 ) prepare the bromide 18, which then follows steps as in Figure 5F. Interestingly, a similar approach relying on the alkylation of a Grignard reagent with a bromide derived from protected aspartate was, in fact, demonstrated experimentally by Liu et al 30 In yet another route in Figure 5H, the program begins with Cbz-protected aspartic anhydride 21, which is opened regioselectively 31 with a Grignard reagent derived from 19. Subsequent tandem reduction-lactonization 32 gives lactone 22 opened with amine 14.…”