Dondoni Alessandro, Massi Alessandro, Minghini Erik, Sabbatini Simona, Bertolasi Valerio
Dipartimento di Chimica, Università di Ferrara, Via L Borsari 46, 44100 Ferrara, Italy.
J Org Chem. 2003 Aug 8;68(16):6172-83. doi: 10.1021/jo0342830.
A novel and versatile strategy for the synthesis of heterocyclic alpha-amino acids has been described. The use of components (aldehyde or beta-ketoester) bearing a masked glycinyl moiety in Biginelli and Hantzsch cyclocondensations allowed access to the 4-dihydropyrimidinyl-alpha-glycines, 4-dihydropyrimidinyl-alpha-alanines, 4-pyridyl-alpha-alanines, and 2-pyridyl-alpha-alanines classes. Dihydropyrimidinyl-amino acids were obtained as a mixture of diastereoisomers due to the formation of the stereocenter at C4 of the dihydropyrimidinone ring. Individual stereoisomers were isolated as pure compounds and their structures were assigned with the aid of X-ray crystallography and chiroptical properties. The enantiomeric purity of a representative selection of the above amino acids was greater than 96% as verified by derivatization to the corresponding Mosher's amides and subsequent (1)H and (19)F NMR spectroscopy. Incorporation of the 4-pyridyl-alpha-alanine derivative into a peptide chain is also described.
已描述了一种合成杂环α-氨基酸的新颖且通用的策略。在Biginelli和Hantzsch环缩合反应中使用带有掩蔽甘氨酰部分的组分（醛或β-酮酯），可得到4-二氢嘧啶基-α-甘氨酸、4-二氢嘧啶基-α-丙氨酸、4-吡啶基-α-丙氨酸和2-吡啶基-α-丙氨酸类化合物。由于在二氢嘧啶酮环的C4处形成了立体中心，二氢嘧啶基氨基酸以非对映异构体混合物的形式获得。将各个立体异构体分离为纯化合物，并借助X射线晶体学和手性光学性质确定其结构。通过衍生化为相应的莫舍尔酰胺并随后进行¹H和¹⁹F NMR光谱分析验证，上述代表性氨基酸的对映体纯度大于96%。还描述了将4-吡啶基-α-丙氨酸衍生物掺入肽链的情况。
