[EN] BUILDING BLOCKS FOR STAPLED PEPTIDES<br/>[FR] BLOCS DE CONSTRUCTION POUR PEPTIDES AGRAFÉS
申请人:AGENCY SCIENCE TECH & RES
公开号:WO2018174826A1
公开(公告)日:2018-09-27
This invention relates to a method for producing an alkenyl 1 -aminocyclopropane-1 -carboxylic acid of Formula I wherein R1 is a protecting group, n is an integer between 1 and 10, and A and B are chiral centres such that when A is S, B is R and when A is R, B is S. The method comprises a stereoselective formation of the cyclopropane moiety by cycloaddition onto a double bond, in a molecule comprising a chiral template, Formula lc. Further provided is the use of Formula I in the production of stapled peptides.
2-hydroxyamide derivatives are produced based on the kineticresolution of racemic 2-hydroxyamides with a diphenylacetyl component and (R)-benzotetramisole ((R)-BTM), a chiral acyl-transfer catalyst, via asymmetric esterification and acylation. It was revealed that a tertiary amide can be used with this novel protocol to achieve high selectivity (22 examples; s-value reaching over 250). The resulting chiral
An object of the present invention is to provide a compound useful as a therapeutic drug for an autoimmune disease such as systemic lupus erythematosus (SLE) and lupus nephritis of SLE patients by suppressing immune cell function by inhibiting proliferation of activated T cells and production of interferon alpha (IFN-α).
The present invention provides a compound represented by formula (I):
wherein R1, R2 and R3 are the same as defined in the specification,
or a pharmaceutically acceptable salt thereof.
This invention relates to a method for producing an alkenyl 1-aminocyclopropane-1-carboxylic acid of Formula I wherein R1 is a protecting group, n is an integer between 1 and 10, and A and B are chiral centres such that when A is S, B is R and when A is R, B is S. The method comprises a stereoselective formation of the cyclopropane moiety by cycloaddition onto a double bond, in a molecule comprising a chiral template, Formula lc. Further provided is the use of Formula I in the production of stapled peptides.
本发明涉及一种生产式 I 的烯基 1-氨基环丙烷-1-羧酸的方法,其中 R1 是保护基团,n 是 1-10 之间的整数,A 和 B 是手性中心,当 A 是 S 时,B 是 R,当 A 是 R 时,B 是 S,该方法包括在包含手性模板的分子中,通过环化到双键上立体选择性地形成环丙烷分子,即式 lc。进一步提供了式 I 在生产钉肽中的用途。
Asymmetric synthesis of substituted 1-aminocyclopropane-1-carboxylic acids from a new chiral glycine equivalent with 3,6-dihydro-2H-1,4-oxazin-2-one structure
作者:Rafael Chinchilla、Larry R Falvello、Nuria Galindo、Carmen Nájera
DOI:10.1016/s0957-4166(98)00244-4
日期:1998.7
Condensation of the new chiral glycine equivalent 10 with aldehydes at room temperature in the presence of K2CO3 under solid-liquid phase-transfer-catalysed conditions afforded stereoselectively new chiral (Z)-alpha,beta-didehydroamino acid (DDAA) derivatives with oxazinone structure 14. These systems have been used in diastereoselective cyclopropanation reactions for the synthesis of enantiomerically pure 1-aminocyclopropanecarboxylic acids (ACCs) such as (-)-allo-norcoronamic and (-)-allo-coronamic acids. (C) 1998 Elsevier Science Ltd. All rights reserved.