C-2-symmetric Val-Val dipeptide isosteres via diethylaluminium azide ring opening of epoxyalcohols

Diethylaluminium azide has been used as a highly regio- and stereo-selectiv e reagent for the ring opening of valine-derived, sterically hindered epoxy alcohols. This reagent has enabled extending a previously described synthes is of diaminodiol dipeptide isosteres (P-1-Psi [CH(OH)-CH(OH)]-P-1') also t o isosteres with branched residues in position P-1'. The new methodology is compatible with Boc and Cbz protection of the starting aminoacid and has b een applied to the synthesis of a C-2-symmetric diaminodiol Val-Val dipepti de isostere 11, starting from the methyl ester of L-valine, in 25% overall yield over seven (for Boc protection) or six (for Cbz protection) passages. A C-2-symmetric di-MEM protected diaminodiol 17 and a mono-Boc protected, desymmetrized derivative 10 have also been obtained by the same approach. C ompounds 10, 11 and 17 can be used as core units Of C-2-symmetric and non-s ymmetric peptidomimetic inhibitors of aspartic proteases and as intermediat es for the synthesis of cyclic urea inhibitors of HIV-protease.