Gellerman G, Elgavi A, Salitra Y, Kramer M
Peptor Ltd, Kiryat Weizmann, Rehovot 76326, Israel.
J Pept Res. 2001 Apr;57(4):277-91. doi: 10.1046/j.1397-002x.2000.0780.x.
Protected Nalpha-(aminoallyloxycarbonyl) and Nalpha-(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 Nalpha-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 alpha,beta-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 (SCAPELs). Nalpha-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.
除脯氨酸外的所有天然氨基酸的Nα-（氨基烯丙氧基羰基）和Nα-（羧基烯丙基）衍生物及其手性翻转剂，采用简便高效的方法合成，然后用于Nα-主链环肽的合成。制备氨基酸构建单元的合成途径包括使用卤代烷、醛和α,β-不饱和羰基化合物以及相应氨基酸进行烷基化、还原胺化和迈克尔加成。然后将所得的氨基酸前体单元进行Fmoc保护，得到光学纯的氨基酸构建单元。根据侧链的性质选择每种氨基酸的合适合成途径，从而得到用于肽环小环类似物（SCAPELs）固相肽合成的完全正交三官能构建单元。构建单元的Nα-氨基用Fmoc保护，功能性侧链用t-Bu/Boc/Trt保护，N-烷基氨基或N-烷基羧基分别用Alloc或烯丙基保护。这种简便的方法能够在短时间内轻松制备大量的氨基酸构建单元，并成功应用于组合化学以及大规模固相肽合成。这些构建单元在肽相关药物的合成中具有显著优势。
