Instituto de Productos Naturales y Agrobiología del CSIC, Avda. Astrofísico Francisco Sánchez, 3, 38206, La Laguna, Tenerife, Spain.
Amino Acids. 2022 Jun;54(6):955-966. doi: 10.1007/s00726-022-03159-z. Epub 2022 Apr 12.
The ability of amino acid "customizable units" to generate structural diversity is illustrated by the conversion of 4-hydroxyproline (Hyp) units into a variety of nitrogen heterocycles. After a first common step, where the unit underwent a one-pot decarboxylation-alkylation reaction to afford 2-alkylpyrrolidines with high stereoselectivity, a divergent step was carried out. Thus, the deprotected 4-hydroxy group was used either to initiate a radical scission that afforded aliphatic β-amino aldehydes, or to carry out an elimination reaction, to give 2-alkyl-2,5-dihydro-1H-pyrroles. In the first case, the amines underwent a tandem reductive amination-cyclization to afford β-amino-δ-lactams, an efficient rigidifying unit in peptides. Different lactam N-substituents, such as alkylamines, peptides, and alkenyl chains suitable for olefin metathesis were introduced this way. In the second case, the pyrrole derivatives were efficiently converted into alkaloid and iminosugar derivatives in good global yields and with excellent stereoselectivity.
氨基酸“可定制单元”生成结构多样性的能力体现在将 4-羟脯氨酸（Hyp）单元转化为各种含氮杂环上。经过第一个共同步骤，其中单元经历一锅脱羧-烷基化反应以高立体选择性得到 2-烷基吡咯烷，然后进行发散步骤。因此，未保护的 4-羟基基团要么用于引发自由基断裂，得到脂肪族β-氨基醛，要么进行消除反应，得到 2-烷基-2,5-二氢-1H-吡咯。在第一种情况下，胺经历串联的还原胺化-环化反应，得到β-氨基-δ-内酰胺，这是肽中的有效刚性单元。通过这种方式引入了不同的内酰胺 N-取代基，如烷基胺、肽和适合烯烃复分解的烯基链。在第二种情况下，吡咯衍生物以良好的总收率和优异的立体选择性有效地转化为生物碱和亚氨基糖衍生物。
