Dab9 derivatives of lipopeptide antibiotics and methods of making and using the same

An antimicrobial compound according to structural formula (III):

• or pharmaceutically acceptable salt thereof, wherein:
• R3 is independently selected from hydrogen, (C1–C25) alkyl optionally substituted with one or more of the same or different R15 groups, (C1–C25) heteroalkyl optionally substituted with one or more of the same or different R15 groups, (C5–C10) aryl optionally substituted with one or more of the same or different R15 groups, (C5–C15) arylaryl optionally substituted with one or more of the same or different R15 groups, (C5–C15) biaryl optionally substituted with one or more of the same or different R15 groups, 5–10 membered heteroaryl optionally substituted with one or more of the same or different R15 groups, (C6–C26) arylalkyl optionally substituted with one or more of the same or different R15 groups, 6–26 membered heteroarylalkyl optionally substituted with one or more of the same or different R15 groups, and a linear or branched, saturated or singly or multiply unsaturated alkyl or hydroxy alkyl having a chain of 6 to 22 carbon atoms;
• R4 is Asp or Asn;
• R6 is independently selected from at least one amino acid, a substituent comprising a primary or secondary amine, (C1–C25) alkyl optionally substituted with one or more of the same or different R15 groups, (C1–C25) heteroalkyl optionally substituted with one or more of the same or different R15 groups, (C5–C10) aryl optionally substituted with one or more of the same or different R15 groups, (C5–C15) arylaryl optionally substituted with one or more of the same or different R15 groups, (C5–C15) biaryl optionally substituted with one or more of the same or different R15 groups, 5–10 membered heteroaryl optionally substituted with one or more of the same or different R15 groups, (C6–C26) arylalkyl optionally substituted with one or more of the same or different R15 groups, and 6–26 membered heteroarylalkyl optionally substituted with one or more of the same or different R15 groups;
• each R15 is independently selected from —OR16, —SR16, NR16R16, —CN, —NO2, —N3, —C(O)OR16, —C(O)NR16R16, —C(S)NR16R16, —C(NR16)NR16R16, —CHO, —R16CO, —SO2R16, —SOR16, —PO(OR16)2, —PO(OR16), —CO2H, —SO3H, —PO3H, halogen, and trihalomethyl;
• and
• each R16 is independently selected from hydrogen, (C1–C6) alkyl, (C5–C10) aryl, 5–10 membered heteroaryl, (C6–C16) arylalkyl, and 6–16 membered heteroarylalkyl.