Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-10954272-B2
Publication Date
2021-03-23
Expiration Date
Abstract
The present invention relates to a process for acylating cyclic peptides bearing an amino group and to the application of said process in the preparation of anidulafungin and micafungin.
Core Innovation
The invention concerns a method for selectively acylating a cyclic peptide bearing an amino group at the amino group without protecting the hydroxyl groups of the cyclic peptide prior to the acylation step, to form a cyclic lipopeptide. An acid R1CO2H is reacted with a compound of general formula (1) to give a compound of general formula (2), and the compound of general formula (2) is then mixed with the unprotected cyclic peptide bearing an amino group to selectively acylate the cyclic peptide at the amino group.
The approach is directed to acylating an unprotected echinocandin B nucleus, including FR 179642 and salts thereof, at the amino group while keeping the peptide hydroxyl groups unprotected prior to acylation. The framework includes R1 substituents that include alkyl comprising from 10 to 25 carbon atoms, substituted alkyl comprising from 10 to 25 carbon atoms, aryl comprising from 10 to 25 carbon atoms, or substituted aryl comprising from 10 to 25 carbon atoms, with R2 being alkyl and R3 and R4 being alkyl, substituted alkyl, halogen, hydrogen, or NO2.
The invention further provides methods for preparation of anidulafungin or a pharmaceutically acceptable salt thereof by contacting an unprotected echinocandin B nucleus with a compound of general formula (2) in the presence of a base to selectively acylate the amino group. The anidulafungin salt obtained is isolated, converted into a pharmaceutically acceptable salt of anidulafungin, and that pharmaceutically acceptable salt is isolated.
Claims Coverage
The document contains two independent claims covering a general selective acylation method to form cyclic lipopeptides from unprotected cyclic peptides bearing an amino group, and a preparation method for anidulafungin or its pharmaceutically acceptable salt using selective acylation of an unprotected echinocandin B nucleus with subsequent isolation and salt conversion. The independent claims collectively define three inventive features.
Selective acylation without protecting hydroxyl groups to form a cyclic lipopeptide
React an acid R1CO2H with a compound of general formula (1) to give a compound of general formula (2), then mix said compound of general formula (2) with an unprotected cyclic peptide bearing an amino group to selectively acylate the cyclic peptide at the amino group to form a cyclic lipopeptide, without protecting the hydroxyl groups of the cyclic peptide prior to the acylation step.
Acylation of an unprotected echinocandin B nucleus to prepare anidulafungin
Prepare anidulafungin or a pharmaceutically acceptable salt thereof by contacting an unprotected echinocandin B nucleus unprotected at the hydroxyl groups with a compound of general formula (2) in the presence of a base to selectively acylate the amino group.
Isolation and salt conversion of anidulafungin
Isolate the anidulafungin salt obtained, convert it into a pharmaceutically acceptable salt of anidulafungin, and isolate the pharmaceutically acceptable salt.
Overall, claim coverage centers on making an activated intermediate of general formula (2) from an acid R1CO2H via general formula (1), then selectively acylating the amino group of an unprotected cyclic peptide, particularly an unprotected echinocandin B nucleus, to form cyclic lipopeptides and anidulafungin salts through isolation and salt conversion steps.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
Interested in licensing this patent?