Merck Center for Catalysis at Princeton University, Washington Road, Princeton, NJ, 08544, USA.
Bristol-Myers Squibb, Route 206 & Province Line Road, Princeton, NJ, 08543, USA.
Angew Chem Int Ed Engl. 2017 Jan 16;56(3):728-732. doi: 10.1002/anie.201608207. Epub 2016 Nov 17.
A method for the decarboxylative macrocyclization of peptides bearing N-terminal Michael acceptors has been developed. This synthetic method enables the efficient synthesis of cyclic peptides containing γ-amino acids and is tolerant of functionalities present in both natural and non-proteinogenic amino acids. Linear precursors ranging from 3 to 15 amino acids cyclize effectively under this photoredox method. To demonstrate the preparative utility of this method in the context of bioactive molecules, we synthesized COR-005, a somatostatin analogue that is currently in clinical trials.
现已开发出一种用于含 N-端迈克尔受体的肽的脱羧环化缩合的方法。这种合成方法能够高效合成含有γ-氨基酸的环肽，并且对天然和非天然氨基酸中存在的官能团具有耐受性。在此光氧化还原方法下，线性前体（从 3 个到 15 个氨基酸）可以有效地环化。为了证明该方法在生物活性分子中的制备实用性，我们合成了 COR-005，这是一种目前正在临床试验中的生长抑素类似物。
