Patent ID: 7015307

Claim:
A method of purifying a compound of formula I: wherein: R 19 is hydrogen; R 20 is —R a —Y—R b -(Z) x , R f , —C(O)R f , or —C(O)—R a —Y—R b -(Z) x ; R 3 is —OR c , —NR c R c , —O—R a —Y—R b -(Z) x , —NR c —R a —Y—R b -(Z) x , —NR c R e , or —O—R e ; or R 3 is a nitrogen-linked, oxygen-linked, or sulfur-linked substituent that comprises one or more phosphono groups; R 5 is selected from the group consisting of hydrogen, halo, —CH(R c )—NR c R c , —CH(R c )—NR c R e , —CH(R c )—NR c —R a —Y—R b -(Z) x , —CH(R c )—R x , —CH(R c )—NR c —R a —C(═O)—R x , and a substituent that comprises one or more phosphono groups; each R a is independently selected from the group consisting of alkylene, substituted alkylene, alkenylene, substituted alkenylene, alkynylene and substituted alkynylene; each R b is independently selected from the group consisting of a covalent bond, alkylene, substituted alkylene, alkenylene, substituted alkenylene, alkynylene and substituted alkynylene, provided R b is not a covalent bond when Z is hydrogen; each R c 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)R d ; each R d 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; R e is a saccharide group; each R f is independently alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl, or heterocyclic; R x 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—, —NR c —, —S(O)—, —SO 2 —, —NR c C(O)—, —OSO 2 —, —OC(O)—, —NR c SO 2 —, —C(O)NR c —, —C(O)O—, —SO 2 NR c —, —SO 2 O—, —P(O)(OR c )O—, —P(O)(OR c )NR c —, —OP(O)(OR c )O—, —OP(O)(OR c )NR c —, —OC(O)O—, —NR c C(O)O—, —NR c C(O)NR c —, —OC(O)NR c —, —C(═O)—, and —NR c SO 2 NR c —; 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 R 3 and R 5 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 polystyrene divinyl benzene resin; (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.