Building blocks for stapled peptides
AssigneeAgency for Science, Technology and Research
InventorsTsz Ying Yuen, Charles William Johannes, Greg Verdine
Life of this patent
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Abstract
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.
Claims19
A method for producing a compound of Formula I
- wherein:
- R1 is a protecting group;
- n is an integer between 1 and 10, and;
- A and B are chiral centers such that when A is S, B is R and when A is R, B is S;
- said method comprising the steps of:
- a) condensing a chiral compound of Formula Ia
- with a compound of Formula Ib
- to produce a compound of Formula Ic
- wherein A is a chiral center, R2 is an aliphatic group with a tertiary or quaternary carbon atom covalently bonded to the chiral center A, and R3 is aryl or heteroaryl;
- b) reacting the non-terminal carbon-carbon double bond formed in step a) to produce a cyclopropyl group, so as to form a compound of Formula Id and;
- c) hydrolyzing the compound of Formula Id and protecting a free amine produced by the hydrolysis with a reagent comprising R1 to produce the compound of Formula I.
A compound of Formula I
- wherein:
- R1 is a protecting group;
- n is an integer between 1 and 10, and;
- A and B are chiral centers such that when A is 5, B is R and when A is K, B is S.
Dependencies are inferred from the claim text.