Facile synthesis of orthogonally protected amino acid building blocks for combinatorial N-backbone cyclic peptide chemistry

G. Gellerman, A. Elgavi, Y. Salitra, M. Kramer

نتاج البحث: نشر في مجلةمقالةمراجعة النظراء

32 اقتباسات (Scopus)

ملخص

Protected Nα-(aminoallyloxycarbonyl) and Nα-(carboxyallyl) derivatives of all natural amino acids (except proline), and their chiral inverters, were synthesized using facile and efficient methods and were then used in the synthesis of Nα-backbone cyclic peptides. Synthetic pathways for the preparation of the amino acid building units included alkylation, reductive amination and Michael addition using alkylhalides, aldehydes and α,β-unsaturated carbonyl compounds, and the corresponding amino acids. The resulting amino acid prounits were then subjected to Fmoc protection affording optically pure amino acid building units. The appropriate synthetic pathway for each amino acid was chosen according to the nature of the side-chain, resulting in fully orthogonal trifunctional building units for the solid-phase peptide synthesis of small cyclic analogs of peptide loops (SCAPLs™). Nα-amino groups of building units were protected by Fmoc, functional side-chains were protected by t-Bu/Boc/Trt and N-alkylamino or N-alkylcarboxyl were protected by Alloc or Allyl, respectively. This facile method allows easy production of a large variety of amino acid building units in a short time, and is successfully employed in combinatorial chemistry as well as in large-scale solid-phase peptide synthesis. These building units have significant advantage in the synthesis of peptido-related drugs.

اللغة الأصليةالإنجليزيّة
الصفحات (من إلى)277-291
عدد الصفحات15
دوريةJournal of Peptide Research
مستوى الصوت57
رقم الإصدار4
المعرِّفات الرقمية للأشياء
حالة النشرنُشِر - 2001
منشور خارجيًانعم

بصمة

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