Process for purifying glycopeptide phosphonate derivatives

A method of purifying a compound of formula I:

• 7
• wherein:
• R19 is hydrogen;
• R20 is —Ra—Y—Rb-(Z)x, Rf, —C(O)Rf, or —C(O)—Ra—Y—Rb-(Z)x;
• R3 is —ORc, —NRcRc, —O—Ra—Y—Rb-(Z)x, —NRc—Ra—Y—Rb-(Z)x, —NRcRe, or —O—Re;
• or R3 is a nitrogen-linked, oxygen-linked, or sulfur-linked substituent that comprises one or more phosphono groups;
• R5 is selected from the group consisting of hydrogen, halo, —CH(Rc)—NRcRc, —CH(Rc)NRcRe, —CH(Rc)—NRc—Ra—Y—Rb-(Z)x, —CH(Rc)—Rx, —CH(Rc)—NRc—Ra—C(═O)—Rx, and a substituent that comprises one or more phosphono groups;
• each Ra is independently selected from the group consisting of alkylene, substituted alkylene, alkenylene, substituted alkenylene, alkynylene and substituted alkynylene;
• each Rb is independently selected from the group consisting of a covalent bond, alkylene, substituted alkylene, alkenylene, substituted alkenylene, alkynylene and substituted alkynylene, provided R bis not a covalent bond when Z is hydrogen;
• each Rc is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl, heterocyclic and —C(O)Rd;
• each Rd is independently selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic;
• Re is a saccharide group;
• each Rf is independently alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl, or heterocyclic;
• Rx is an N-linked amino saccharide or an N-linked heterocycle;
• each Y is independently selected from the group consisting of oxygen, sulfur, —S—S—, —NRc—, —S(O)—, —SO2—, —NRcC(O)—, —OSO2—, —OC(O)—, —NRcSO2—, —C(O)NRc—, —C(O)O—, —SO2NRc—, —SO2O—, —P(O)(ORc)O—, —P(O)(ORc)NRc—, —OP(O)(ORc)O—, —OP(O)(ORc)NRc—, —OC(O)O—, —NRcC(O)O—, —NRcC(O)NRc—, —OC(O)NRc—, —C(═O)—, and —NRcSO2NRc—;
• each Z is independently selected from hydrogen, aryl, cycloalkyl, cycloalkenyl, heteroaryl and heterocyclic;
• and
• x is 1 or 2;
• or a pharmaceutically acceptable salt, stereoisomer, or prodrug thereof;
• provided at least one of R3 and R5 is a substituent comprising one or more phosphono groups;
• the method comprising the steps of:
• (a) contacting a first acidified aqueous solution comprising a compound of formula I with a resin comprising polystyrene and divinyl benzene;
• (b) eluting the contacted resin with a second acidified aqueous solution comprising a polar organic solvent to form an eluate;
• and
• (c) isolating the compound of formula I from the eluate.