Natural product antibiotics and analogs thereof

A method of treating a bacterial infection in a subject comprising administering an effective amount of a compound of Formula (II):

• or a pharmaceutically acceptable salt thereof, to the subject;
• wherein:
• each occurrence of R1, R2, R4a, R4b, R5a, and R5b, is independently hydrogen or halogen;
• RB is hydrogen, substituted or unsubstituted C1-3 alkyl, —C(═O)RB2, —C(═O)ORB1, —C(═O)SRB1, —C(═O)N(RB1)2, —S(═O)2RB2, —S(═O)2ORB1, —P(═O)2RB2, —P(═O)2ORB1, —P(═O)(ORB1)2, —P(═O)(RB2)2, or —P(═O)(RB2)(ORB1);
• RC is hydrogen, substituted or unsubstituted C1-3 alkyl, —C(═O)RC2, —C(═O)ORC1, —C(═O)SRC1, —C(═O)N(RC1)2, —S(═O)2RC2, —S(═O)2ORC1, —P(═O)2RC2, —P(═O)2ORC1, —P(═O)(ORC1)2, —P(═O)(RC2)2, or —P(═O)(RC2)(ORC1);
• each occurrence of RB1 and RC1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, or a nitrogen protecting group when attached to a nitrogen atom;
• or two RB1 groups and/or two RC1 groups are joined to form an substituted or unsubstituted heterocyclic or substituted or unsubstituted heteroaryl ring;
• each occurrence of RB2 and RC2 is independently substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• and
• R6 is substituted or unsubstituted C1-C6alkyl.

A method of treating a bacterial infection in a subject comprising administering an effective amount of a compound of Formula (IV):

• or a pharmaceutically acceptable salt thereof, to the subject;
• wherein:
• each occurrence of R7, R8, and R9 is independently hydrogen or halogen;
• each occurrence of RD1, RD2, RD3, and RD4 is independently hydrogen, substituted or unsubstituted C1-3 alkyl, —C(═O)RD6, —C(═O)ORD5, —C(═O)SRD5, —C(═O)N(RD5)2, —S(═O)2RD6, —S(═O)2ORD5, —P(═O)2RD6, —P(═O)2ORD5, —P(═O)(ORD5)2, —P(═O)(RD6)2, or —P(═O)(RD6)(ORD5);
• each occurrence of RD5 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, or a nitrogen protecting group when attached to a nitrogen atom;
• or two RD5 groups are joined to form an substituted or unsubstituted heterocyclic or substituted or unsubstituted heteroaryl ring;
• each occurrence of RD6 is independently substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R10 is a group of formula:
• wherein each instance of R11a, R11b, R12a, R12b, R13a, and R13b is independently hydrogen, substituted or unsubstituted C1-3 alkyl, or halogen;
• R14 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• RE is hydrogen, substituted or unsubstituted C1-3 alkyl, —C(═O)RE2, —C(═O)ORE1, —C(═O)SRE1, —C(═O)N(RE1)2, —S(═O)2RE2, —S(═O)2ORE1, —P(═O)2RE2, —P(═O)2ORE1, —P(═O)(ORE1)2, —P(═O)(RE2)2, or —P(═O)(RE2)(ORE1);
• each occurrence of RE1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, or a nitrogen protecting group when attached to a nitrogen atom;
• or two RE1 groups are joined to form an substituted or unsubstituted heterocyclic or substituted or unsubstituted heteroaryl ring;
• RE2 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• RF is hydrogen, substituted or unsubstituted C1-3 alkyl, —C(═O)RF2, —C(═O)ORF1, —C(═O)SRF1, —C(═O)N(RF1)2, —S(═O)2RF2, —S(═O)2ORF1, —P(═O)2RF2, —P(═O)2ORF1, —P(═O)(ORF1)2, —P(═O)(RF2)2, or —P(═O)(RF2)(ORF1);
• each occurrence of RF1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, or a nitrogen protecting group when attached to a nitrogen atom;
• or two RF1 groups are joined to form an substituted or unsubstituted heterocyclic or substituted or unsubstituted heteroaryl ring;
• and
• RF2 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

A method of identifying an inhibitor of bacterial sugar fermentation in a bacterial strain, the method comprising:

• (a) combining a candidate compound and a bacterial strain in which sugar transport depends on the phosphoenolpyruvate phosphotransferase system thereby producing a combination;
• (b) culturing the combination in media comprising a sugar and one or more pH indicators under conditions appropriate for sugar fermentation by the bacterial strain;
• and
• (c) determining if sugar fermentation occurs in the combination cultured in (b), wherein if sugar fermentation does not occur or is reduced in the combination cultured in (b), relative to the extent to which fermentation occurs under the same conditions except that the candidate compound is not present, the candidate compound is an inhibitor of bacterial sugar fermentation.