Proton acceptor iminium/carbocation-type coupling agents
AssigneeLuxembourg Bio Technologies Ltd.
InventorsFernando Albericio, Ayman El-Faham, Yoav Luxembourg, Ariel Ewenson
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Abstract
Novel iminium-type coupling agents containing proton acceptors in their iminium moiety, which can be used beneficially as coupling agents in various chemical polypeptide and/or polynucleotide syntheses, and are particularly useful as yield enhancing and racemization suppressing coupling agents for use in peptide syntheses, are disclosed. Further disclosed are a process of preparing such iminium-type coupling agents and their use in the preparation of polypeptides and/or polynucleotides.
Claims44
A coupling agent having a formula selected from the group consisting of:
- wherein:
- A is an inorganic anion;
- L is a leaving group selected from the group consisting of a benzotriazole, a benzotriazinone, a succinimide, a ketoxime, a pyridin-2(1H)-one-1-oxy, a quinazolin-4(3H)-one-3-oxy, a 1H-benzo[d]imidazol-1-oxy, an imidazole, an indolinone-1-oxy, pentafluorophenol, pentafluorothiophenol, 2-nitrophenol and 2-nitrobenzenethiol;
- n is an integer from 1 to 4,
- R1, R2, R3, R4, R5 and R6 are each independently an alkyl having 1-4 carbon atoms, or one of R1 and R2, and/or R3 and R4, and/or R5 and R6 are independently joined to form a heteroalicyclic moiety selected from the group consisting of pyrrolidine, piperidine, morpholine, a thiomorpholine, a imidazolidine, an azaphosphinane, an azaphospholidine, an azaborinane, an azaborolidine, and a piperazine,
- provided that one of R1 and R2, and/or R3 and R4, and/or R5 and R6 are joined to form said heteroalicyclic moiety.
A coupling agent selected from the group consisting of:
A coupling agent being
A coupling agent having a formula selected from the group consisting of:
- wherein:
- A is an inorganic anion;
- L is a ketoxime leaving group having the Formula VI:
- Z4 and Z5 are each independently selected from the group consisting of F, Cl, Br, CORa, COORa, CONRa, CN, CF3 or NO2 and Ra is;
- n is an integer from 1 to 4,
- R1, R2, R3, R4, R5 and R6 are each independently an alkyl having 1-4 carbon atoms and an alkyl having 1-4 carbon atoms or R1 and R2, and/or R3 and R4, and/or R5 and R6 are each independently joined to form a heteroalicyclic moiety selected from the group consisting of a pyrrolidine, piperidine, morpholine, a thiomorpholine, a imidazolidine, an azaphosphinane, an azaphospholidine, an azaborinane, an azaborolidine, and a piperazine,
- provided that:
- at least one of R1 and R2, and/or R3 and R4, and/or R5 and R6 are joined to form said heteroalicyclic moiety.
A coupling agent being
Dependencies are inferred from the claim text.