申请人:Saulnier Mark G.
公开号:US20130281657A1
公开(公告)日:2013-10-24
The invention provides methods of preparing macrocycles including macrocycle stabilized peptides (MSPs). Macrocycles and MSPs are prepared according to nucleophilic capture of an iminoquinomethide type intermediate generated from a suitably substituted 2-amino-thiazol-5-yl carbinol. The preferred nucleophile may be selected from an electron rich aromatic moiety in the case of macrocycles and, in the case of MSPs, at least one amino acid comprises an electron rich aromatic moiety. In addition, the concept can be extended to other related 5-membered heterocyclic systems in place of the thiazole, such as imidazole or oxazole. The conditions for the generation of the corresponding iminoquinomethide type intermediates may be similar or different than the conditions used for the 2-amino-thiazol-5-yl carbinol.
本发明提供了制备大环化合物的方法,包括稳定大环化肽(MSPs)。根据适当取代的2-氨基噻唑-5-基甲醇生成的亚胺喹啉甲烷型中间体的亲核捕获,制备大环和MSP。在大环的情况下,首选亲核试剂可以从富电子芳香基团中选择,在MSP的情况下,至少有一种氨基酸包含富电子芳香基团。此外,该概念可以扩展到取代噻唑的其他相关5-成员杂环系统,例如咪唑或噁唑。生成相应的亚胺喹啉甲烷型中间体的条件可能与用于2-氨基噻唑-5-基甲醇的条件相似或不同。