C2-symmetric Val-Val dipeptide isosteres via diethylaluminium azide ring opening of epoxyalcohols
| Autor: | Fabio Benedetti, Miertus, S., Norbedo, S. |
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| Přispěvatelé: | Benedetti, Fabio, Miertus, S., Norbedo, S. |
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| Zdroj: | Scopus-Elsevier Croatica Chemica Acta Volume 74 Issue 4 ResearcherID |
| ISSN: | 0011-1643 1334-417X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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