Original scientific paper

C₂-Symmetric Val-Val Dipeptide Isosteres via Diethylaluminium Azide Ring Opening of Epoxyalcohols

Fabio Benedetti ; Department of Chemical Sciences, University of Trieste, Via L. Giorgieri 1, 1-34127 Trieste, Italy
Stanislav Miertus ; International Centre for Science and High Technology, UNIDO, Trieste, Italy
Stefano Norbedo ; Department of Chemical Sciences, University of Trieste, Via L. Giorgieri 1, 1-34127 Trieste, Italy

Abstract

Diethylaluminium azide has been used as a highly regio- and stereo-selective reagent for the ring opening of valine-derived, sterically hindered epoxyalcohols. This reagent has enabled extending a previously described synthesis of diaminodiol dipeptide isosteres (P1-Ψ[CH(OH)-CH(OH)]-P₁') also to isosteres with branched residues in position P₁'. The new methodology is compatible with Boe and Cbz proteetion of the starting aminoacid and has been applied to the synthesis of a C₂-symmetric diaminodiol Val-Val dipeptide isostere 11, starting from the methyl ester of L-valine, in 25% over-all yield over seven (for Boe proteetion) or six (for Cbz proteetion) passages. A C₂-symmetric di-MEM proteeted diaminodiol 17 and a mono-Boc proteeted, desymmetrized derivative 10 have also been obtained by the same approach. Compounds 10, 11 and 17 can be used as core units of C₂-symmetric and non-symmetric peptido-mimetic inhibitors of aspartic proteases and as intermediates for the synthesis of cyclic urea inhibitors of HIV-protease.

Keywords

diethylaluminium azide; epoxyalcohol; diaminodiol dipeptide isostere; ring opening

Hrčak ID:

131953

URI

https://hrcak.srce.hr/131953

Publication date:

1.11.2001.

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