Synthesis of orthogonally protected optically pure ketopiperazine, diketopiperazine, ketodiazepane, and 3-aminopyrrolidone building blocks for peptidomimetic combinatorial chemistry

Gary Gellerman, Eran Hazan, Marina Kovaliov, Amnon Albeck, Shimon Shatzmiler

פרסום מחקרי: פרסום בכתב עתמאמרביקורת עמיתים

12 ציטוטים ‏(Scopus)

תקציר

A simple and convenient synthesis of orthogonally protected multi-tethered, optically pure 2-ketopiperazine, diketopiperazine, 2-ketodiazepane and 3-aminopyrrolidone scaffolds for Fmoc combinatorial chemistry has been developed. It utilizes accessible chiral amino acid precursors, sequentially applying reductive alkylation, dipeptide coupling and regioselective ring formation as key steps. These scaffolds are expansion of our 'pool of privileged building blocks' and can introduce valuable drug-like properties in three independent directions to any medicinally relevant piperazine-, diazepane- and pyrrolidone-based motif by 'around-the-scaffold' drug optimization. The synthetic routes reported in this work are general and applicable for the preparation of a diverse library of scaffolds, controlling chirality, arm position and length as well as the nature of functional moieties at the arms for further diversification in three independent directions. In addition, these building blocks have a wide application scope in managing fast and efficient multi-cyclic optimization processes in the combinatorial chemistry and drug design fields.

שפה מקוריתאנגלית
עמודים (מ-עד)1389-1396
מספר עמודים8
כתב עתTetrahedron
כרך65
מספר גיליון7
מזהי עצם דיגיטלי (DOIs)
סטטוס פרסוםפורסם - 14 פבר׳ 2009

טביעת אצבע

להלן מוצגים תחומי המחקר של הפרסום 'Synthesis of orthogonally protected optically pure ketopiperazine, diketopiperazine, ketodiazepane, and 3-aminopyrrolidone building blocks for peptidomimetic combinatorial chemistry'. יחד הם יוצרים טביעת אצבע ייחודית.

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