Cross-linked glycopeptide - cephalosporin antibiotics

A compound of formula II:

• or a salt thereof;
• wherein
• P1 and P2 are independently hydrogen or an amino-protecting group;
• P3 is hydrogen or a carboxy-protecting group;
• Q is a leaving group or a group of the formula:
• wherein
• R1 is —Ya—(W)n—Yb—;
• W is selected from the group consisting of —O—, —N(Rd)—, —S, —S(O)—, —S(O)2—, C3-6 cycloalkylene, C6-10 arylene and C2-9 heteroarylene;
• wherein each arylene, cycloalkylene and heteroarylene group is optionally-substituted with 1 to 3 substituents independently selected from Rb;
• Ya and Yb are independently C1-5 alkylene, or when W is cycloalkylene, arylene or heteroarylene, Ya and Yb are independently selected from the group consisting of a covalent bond and C1-5 alkylene;
• wherein each alkylene group is optionally substituted with 1 to 3 substituents independently selected from —ORd, —NRdRe, —CO2Rd, —C(O)NRdRe and —S(O)2NRdRe;
• R2 is hydrogen or C1-6 alkyl;
• each R3 is independently selected from the group consisting of C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C6-10 aryl, C2-9 heteroaryl, C3-6 heterocyclic and Ra;
• or two adjacent R3 groups are joined to form C3-6 alkylene or —O— (C1-6 alkylene)-O—;
• wherein each alkyl, alkylene, alkenyl and alkynyl group is optionally substituted with 1 to 3 substitutents independently selected from the group consisting of Ra and Rc;
• and each aryl, cycloalkyl, heteroaryl and heterocyclic group is optionally substituted with 1 to 3 substitutents independently selected from the group consisting of Rb;
• each Ra is independently selected from the group consisting of —ORd, halo, —SRd, —S(O)Rd, —S(O)2Rd, —S(O)2ORd, —S(O)2NRdRe, —NRdRe, —CO2Rd, —OC(O)Rd, —C(O)NRdRe, —NRdC(O)Re, —OC(O)NRdRe, —NRdC(O)ORe, —NRdC(O)NRdRe, —CF3 and —OCF3;
• each Rb is independently selected from the group consisting of C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and Ra;
• each Rc is independently selected from the group consisting of C3-6 cycloalkyl, C6-10 aryl, C2-9 heteroaryl and C3-6 heterocyclic;
• wherein each cycloalkyl, aryl, heteroaryl and heterocyclic group is optionally substituted with 1 to 3 substituents independently selected from the group consisting of C1-6 alkyl and Rf;
• each Rd and Re is independently selected from the group consisting of hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C6-10 aryl, C2-9 heteroaryl and C3-6 heterocyclic;
• or Rd and Re are joined, together with the atoms to which they are attached, to form a C3-6 heterocyclic ring having 1 to 3 heteroatoms independently selected from oxygen, nitrogen or sulfur;
• wherein each alkyl, alkenyl and alkynyl group is optionally substituted with 1 to 3 substituents independently selected from the group consisting of Rc and Rf;
• and each aryl, cycloalkyl, heteroaryl and heterocyclic group is optionally substituted with 1 to 3 substituents independently selected from the group consisting of C1-6 alkyl and Rf;
• each Rf is independently selected from the group consisting of —OH, —OC1-6 alkyl —SC1-6 alkyl, —F, —Cl, —NH2, —NH(C1-6 alkyl), —N(C1-6 alkyl)2, —OC(O)C1-6 alkyl, —C(O)OC1-6 alky, —NHC(O)C1-6 alky, —C(O)OH, —C(O)NH2, —C(O)NHC1-6 alkyl, —C(O)N(C1-6 alkyl)2, —CF3 and —OCF3;
• X− is an optionally present anion;
• m is 0, 1, 2 or 3;
• and
• n is 0 or 1.

A compound of formula III:

• or salts thereof;
• wherein
• P1 and P2 are independently hydrogen or an amino-protecting group;
• P4 is hydrogen or a carboxy-protecting group;
• R1 is —Ya—(W)n—Yb—;
• W is selected from the group consisting of —O—, —N(Rd)—, —S—, —S(O)—, —S(O)2—, C3-6 cycloalkylene, C6-10 arylene and C2-9 heteroarylene;
• wherein each arylene, cycloalkylene and heteroarylene group is optionally substituted with 1 to 3 substituents independently selected from Rb;
• Ya and Yb are independently C1-5 alkylene, or when W is cycloalkylene, arylene or heteroarylene, Ya and Yb are independently selected from the group consisting of a covalent bond and C1-5 alkylene;
• wherein each alkylene group is optionally substituted with 1 to 3 substituents independently selected from —ORd, —NRdRe, —CO2Rd, —C(O)NRdRe and —S(O)2NRdRe;
• R2 is hydrogen or C1-6 alkyl;
• each Ra is independently selected from the group consisting of —ORd, halo, —SRd, —S(O)Rd, —S(O)2Rd, —S(O)2ORd, —S(O)2NRdRe, —NRdRe, —CO2Rd, —OC(O)Rd, —C(O)NRdRe, NRdC(O)Re, —OC(O)NRdRe, —NRdC(O)ORe, —NRdC(O)NRdRe, —CF3 and OCF3;
• each Rb is independently selected from the group consisting of C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and Ra;
• each Rc is independently selected from the group consisting of C3-6 cycloalkyl, C6-10 aryl, C2-9 heteroaryl and C3-6 heterocyclic;
• wherein each cycloalkyl, aryl, heteroaryl and heterocyclic group is optionally substituted with 1 to 3 substituents independently selected from the group consisting of C1-6 alkyl and Rf;
• each Rd and Re is independently selected from the group consisting of hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C6-10 aryl, C2-9 heteroaryl and C3-6 heterocyclic;
• or Rd and Re are joined, together with the atoms to which they are attached, to form a C3-6 heterocyclic ring having 1 to 3 heteroatoms independently selected from oxygen, nitrogen or sulfur;
• wherein each alkyl, alkenyl and alkynyl group is optionally substituted with 1 to 3 substituents independently selected from the group consisting of Rc and Rf;
• and each aryl, cycloalkyl, heteroaryl and heterocyclic group is optionally substituted with 1 to 3 substituents independently selected from the group consisting of C1-6 alkyl and Rf;
• each Rf is independently selected from the group consisting of —OH, —OC1-6 alkyl, —SC1-6 alkyl, —F, —Cl, —NH2, —NH(C1-6 alkyl), —N(C1-6 alkyl)2, —OC(O)C1-6 alkyl, —C(O)OC1-6 alkyl, —NHC(O)C1-6 alkyl, —C(O)OH, —C(O)NH2, —C(O)NHC1-6 alkyl, —C(O)N(C1-6 alkyl)2, —CF3 and —OCF3;
• and
• n is 0 or 1.