Host targeted inhibitors of dengue virus and other viruses

A compound of Formula (II):

• or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof;
• wherein:
• Ring A is aryl, arylalkenyl, or heteroaryl;
• each instance of RA is independently selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —ORA1, —N(RA1)2, —SRA1, —CN, —C(═NRA1)RA1, —C(═NRA1)ORA1, —C(═NRA1)SRA1, —C(═NRA1)N(RA1)2, —C(═O)NRA1—, —NRA1C(═O)—, —C(═O)RA1, —C(═S)RA1, —C(═S)ORA1, —C(═S)SRA1, —C(═S)N(RA1)2, —NO2, —N3, —N(RA1)3+F−, —N(RA1)3+Cl−, —N(RA1)3+Br−, —N(RA1)3+I−, —N(ORA1)RA1, —NRA1C(═O)RA1, —NRA1C(═O)ORA1, —NRA1C(═O)SRA1, —NRA1C(═O)N(RA1)2, —NRA1C(═S)RA1, —NRA1C(═S)ORA1, —NRA1C(═S)SRA1, —NRA1C(═S)N(RA1)2, —NRA1C(═NRA1)RA1, —NRA1C(═NRA1)ORA1, —NRA1C(═NRA1)SRA1, —NRA1C(═NRA1)N(RA1)2, —NRA1S(═O)2RA1, —NRA1S(═O)2ORA1, —NRA1S(═O)2SRA1, —NRA1S(═O)2N(RA1)2, —NRA1S(═O)RA1, —NRA1S(═O)ORA1, —NRA1S(═O)SRA1, —NRA1S(═O)N(RA1)2, —NRA1P(═O), —NRA1P(═O)2, —NRA1P(═O)(RA1)2, —NRA1P(═O)RA1(ORA1), —NRA1P(═O)(ORA1)2, —OC(═O)RA1, —OC(═O)ORA1, —OC(═O)SRA1, —OC(═O)N(RA1)2, —OC(═NRA1)RA1, —OC(═NRA1)ORA1, —OC(═NRA1)N(RA1)2, —OC(═S)RA1, —OC(═S)ORA1, —OC(═S)SRA1, —OC(═S)N(RA1)2, —ON(RA1)2, —OS(═O)RA1, —OS(═O)ORA1, —OS(═O)SRA1, —OS(═O)N(RA1)2, —OS(═O)2RA1, —OS(═O)2ORA1, —OS(═O)2SRA1, —OS(═O)2N(RA1)2, —OP(═O)2, —OP(═O)(RA1)2, —OP(═O)RA1(ORA1), —OP(═O)(ORA1)2, —OP(═O), —OP(RA1)2, —OPRA1(ORA1), —OP(ORA1)2, —OSi(RA1)3, —OSi(RA1)2ORA1, —OSi(RA1)(ORA1)2, —OSi(ORA1)3, —SSRA1, —S(═O)RA1, —S(═O)ORA1, —S(═O)N(RA1)2, —S(═O)2RA1, —S(═O)2ORA1, —S(═O)2N(RA1)2, —SC(═O)RA1, —SC(═O)ORA1, —SC(═O)SRA1, —SC(═O)N(RA1)2, —SC(═S)RA1, —SC(═S)ORA1, —SC(═S)SRA1, —SC(═S)N(RA1)2, —P(RA1)2, —PRA1(ORA1), —P(ORA1)2, —P(═O), —P(═O)(RA1)2, —P(═O)(ORA1)2, —P(═O)RA1(ORA1), —P(═O)2, —B(RA1)2, —B(ORA1)2, —BRA1(ORA1), —Si(RA1)3, —Si(RA1)2ORA1, —SiRA1(ORA1)2, and —Si(ORA1)3, wherein each occurrence of RA1 is independently selected from the group consisting of hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, a nitrogen protecting group when attached to a nitrogen atom, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, or two RA1 groups are joined to form an optionally substituted heterocyclic ring;
• k is 0, 1, 2, 3, 4, or 5;
• Ring C is a carbocyclic, heterocyclic, aryl, or heteroaryl ring;
• each instance of Rj1, Rj2, Rj3, and RC is independently selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —ORC1, —N(RC1)2, —SRC1, —CN, —C(═NRC1)RC1, —C(═NRC1)ORC1, —C(═NRC1)SRC1, —C(═NRC1)N(RC1)2, —C(═O)RC1, —C(═S)RC1, —C(═S)ORC1, —C(═S)SRC1, —C(═S)N(RC1)2, —NO2, —N3, —N(RC1)3+F−, —N(RC1)3+Cl−, —N(RC1)3+Br−, —N(RC1)3+F−, —N(ORC1)RC1, —NRC1C(═O)RC1, —NRC1C(═O)ORC1, —NRC1C(═O)SRC1, —NRC1C(═O)N(RC1)2, —NRC1C(═S)RC1, —NRC1C(═S)ORC1, —NRC1C(═S)SRC1, —NRC1C(═S)N(RC1)2, —NRC1C(═NRC1)RC1, —NRC1C(═NRC1)ORC1, —NRC1C(═NRC1)SRC1, —NRC1C(═NRC1)N(RC1)2, —NRC1S(═O)2RC1, —NRC1S(═O)2ORC1, —NRC1S(═O)2SRC1, —NRC1S(═O)2N(RC1)2, —NRC1S(═O)RC1, —NRC1S(═O)ORC1, —NRC1S(═O)SRC1, —NRC1S(═O)N(RC1)2, —NRC1P(═O), —NRC1P(═O)2, —NRC1P(═O)(RC1)2, —NRC1P(═O)RC1(ORC1), —NRC1P(═O)(OR1)2, —OC(═O)RC1, —OC(═O)ORC1, —OC(═O)SRC1, —OC(═O)N(RC1)2, —OC(═NRC1)RC1, —OC(═NRC1)ORC1, —OC(═NRC1)N(RC1)2, —OC(═S)RC1, —OC(═S)ORC1, —OC(═S)SRC1, —OC(═S)N(RC1)2, —ON(RC1)2, —OS(═O)RC1, —OS(═O)ORC1, —OS(═O)SRC1, —OS(═O)N(RC1)2, —OS(═O)2RC1, —OS(═O)2ORC1, —OS(═O)2SRC1, —OS(═O)2N(RC1)2, —OP(═O)2, —OP(═O)(RC1)2, —OP(═O)RC1(ORC1), —OP(═O)(ORC1)2, —OP(═O), —OP(RC1)2, —OPRC1(ORC1), —OP(ORC1)2, —OSi(RC1)3, —OSi(RC1)2ORC1, —OSi(RC1)(ORC1)2, —OSi(ORC1)3, —SSRC1, —S(═O)RC1, —S(═O)ORC1, —S(═O)N(RC1)2, —S(═O)2RC1, —S(═O)2ORC1, —S(═O)2N(RC1)2, —SC(═O)RC1, —SC(═O)ORC1, —SC(═O)SRC1, —SC(═O)N(RC1)2, —SC(═S)RC1, —SC(═S)ORC1, —SC(═S)SRC1, —SC(═S)N(RC1)2, —P(RC1)2, —PRC1(ORC1), —P(ORC1)2, —P(═O), —P(═O)(RC1)2, —P(═O)(ORC1)2, —P(═O)RC1(ORC1), —P(═O)2, —B(RC1)2, —B(ORC1)2, —BRC1(ORC1), —Si(RC1)3, —Si(RC1)2ORC1, —SiRC1(ORC1)2, and —Si(ORC1)3, wherein each occurrence of RCd is independently selected from the group consisting of hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, a nitrogen protecting group when attached to a nitrogen atom, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, or two RC1 groups are joined to form an optionally substituted heterocyclic ring or optionally substituted heteroaryl ring;
• n is 0, 1, 2, 3, or 4;
• L is a bond or an optionally substituted, branched or unbranched C1-6 hydrocarbon chain;
• RD is any one of Formulae (i-1)-(i-43):
• wherein:
• each instance of RD1 is independently hydrogen, halogen, acyl, 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, —CN, —NO2, —ORD1a, —N(RD1a)2, —SRD1a, —CH2ORD1a, —CH2N(RD1a)2, —CH2SRD1a, —C(═O)RD1a, —C(═O)ORD1a, —C(═O)SRD1a, —C(═O)N(RD1a)2, —C(═S)RD1a, —C(═S)ORD1a, —C(═S)SRD1a, —C(═S)N(RD1a)2, —C(═NRD1a)RD1a, —C(═NRD1a)ORD1a, —C(═NRD1a)SRD1, or —C(═NRD1a)N(RD1a)2, wherein each occurrence of RD1a is independently hydrogen, acyl, 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, or two RD1a, groups are joined to form an substituted or unsubstituted heterocyclic ring;
• each instance of RD2 is independently hydrogen, halogen, acyl, 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, —CN, —NO2, —ORD2a, —N(RD2a)2, —SRD2a, —CH2ORD2a, —CH2N(RD2a)2, —CH2SRD2a, —C(═O)RD2a, —C(═O)ORD2a, —C(═O)SRD2a, —C(═O)N(RD2a)2, —C(═S)RD2a, —C(═S)ORD2a, —C(═S)SRD2a, —C(═S)N(RD2a)2, —C(═NRD2a)RD2a, —C(═NRD2a)ORD2a, —C(═NRD2a)SRD2a, and —C(═NRD2a)N(RD2a)2, wherein each occurrence of RD2a is independently hydrogen, acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl, or two RD2a groups are joined to form an substituted or unsubstituted heterocyclic ring;
• each instance of RD3 is independently hydrogen, halogen, acyl, 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, —ORD3a, —N(RD3a)2, —SRD3a, —CH2ORD3a, —CH2N(RD3a)2, —CH2SRD3a, —C(═O)RD3a, —C(═O)ORD3a, —C(═O)SRD3a, —C(═O)N(RD3a)2, —C(═S)RD3a, —C(═S)ORD3a, —C(═S)SRD3a, —C(═S)N(RD3a)2, —C(═NRD3a)RD3a, —C(═NRD3a)ORD3a, —C(═NRD3a)SRD3a, or —C(═NRD3a)N(RD3a)2 wherein each occurrence of RD3a is independently hydrogen, acyl, 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, or two RD3a groups are joined to form an substituted or unsubstituted heterocyclic ring;
• optionally RD1 and RD3, or RD2 and RD3, or RD1 and RD2 are joined to form an substituted or unsubstituted carbocyclic or substituted or unsubstituted heterocyclic ring;
• RD4 is a leaving group selected from the group consisting of —Br, —Cl, —I, and —OS(═O)wRD4a, wherein w is 1 or 2, and RD4a 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;
• each instance of X1 is independently a bond, —C(═O)—, —SO2—, —NRD5—, optionally substituted alkylene, or optionally substituted heteroarylene, wherein RD5 is hydrogen, C1-6 alkyl, or a nitrogen protecting group;
• each instance of Y is independently O, S, or NRD6, wherein RD6 is hydrogen, C1-6 alkyl, or a nitrogen protecting group;
• and
• each instance of z and z1 is independently 0, 1, 2, 3, 4, 5, or 6, as valency permits.

A compound of Formula (III):

• or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof;
• wherein:
• Ring A is aryl, arylalkenyl, or heteroaryl;
• each instance of RA is independently selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —ORA1, —N(RA1)2, —SRA1, —CN, —C(═NRA1)RA1, —C(═NRA1)ORA1, —C(═NRA1)SRA1, —C(═NRA1)N(RA1)2, —C(═O)NRA1—, —NRA1C(═O)—, —C(═O)RA1, —C(═S)RA1, —C(═S)ORA1, —C(═S)SRA1, —C(═S)N(RA1)2, —NO2, —N3, —N(RA1)3+F—, —N(RA1)3+Cl−, —N(RA1)3+Br−, —N(RA1)3+I−, —N(ORA1)RA1, —NRA1C(═O)RA1, —NRA1C(═O)ORA1, —NRA1C(═O)SRA1, —NRA1C(═O)N(RA1)2, —NRA1C(═S)RA1, —NRA1C(═S)ORA1, —NRA1C(═S)SRA1, —NRA1C(═S)N(RA1)2, —NRA1C(═NRA1)RA1, —NRA1C(═NRA1)ORA1, —NRA1C(═NRA1)SRA1, —NRA1C(═NRA1)N(RA1)2, —NRA1S(═O)2RA1, —NRA1S(═O)2ORA1, —NRA1S(═O)2SRA1, —NRA1S(═O)2N(RA1)2, —NRA1S(═O)RA1, —NRA1S(═O)ORA1, —NRA1S(═O)SRA1, —NRA1S(═O)N(RA1)2, —NRA1P(═O), —NRA1P(═O)2, —NRA1P(═O)(RA1)2, —NRA1P(═O)RA1(ORA1), —NRA1P(═O)(ORA1)2, —OC(═O)RA1, —OC(═O)ORA1, —OC(═O)SRA1, —OC(═O)N(RA1)2, —OC(═NRA1)RA1, —OC(═NRA1)ORA1, —OC(═NRA1)N(RA1)2, —OC(═S)RA1, —OC(═S)ORA1, —OC(═S)SRA1, —OC(═S)N(RA1)2, —ON(RA1)2, —OS(═O)RA1, —OS(═O)ORA1, —OS(═O)SRA1, —OS(═O)N(RA1)2, —OS(═O)2RA1, —OS(═O)2ORA1, —OS(═O)2SRA1, —OS(═O)2N(RA1)2, —OP(═O)2, —OP(═O)(RA1)2, —OP(═O)RA1(ORA1), —OP(═O)(ORA1)2, —OP(═O), —OP(RA1)2, —OPRA1(ORA1), —OP(ORA1)2, —OSi(RA1)3, —OSi(RA1)2ORA1, —OSi(RA1)(ORA1)2, —OSi(ORA1)3, —SSRA1, —S(═O)RA1, —S(═O)ORA1, —S(═O)N(RA1)2, —S(═O)2RA1, —S(═O)2ORA, —S(═O)2N(RA1)2, —SC(═O)RA1, —SC(═O)ORA1, —SC(═O)SRA1, —SC(═O)N(RA1)2, —SC(═S)RA1, —SC(═S)ORA1, —SC(═S)SRA1, —SC(═S)N(RA1)2, —P(RA1)2, —PRA1(ORA1), —P(ORA1)2, —P(═O), —P(═O)(RA1)2, —P(═O)(ORA1)2, —P(═O)RA1(ORA1), —P(═O)2, —B(RA1)2, —B(ORA1)2, —BRA1(ORA1), —Si(RA1)3, —Si(RA1)2ORA1, —SiRA1(ORA1)2, and —Si(ORA1)3, wherein each occurrence of RA1 is independently selected from the group consisting of hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, a nitrogen protecting group when attached to a nitrogen atom, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, or two RA1 groups are joined to form an optionally substituted heterocyclic ring;
• k is 0, 1, 2, 3, 4, or 5;
• Ring C is a carbocyclic, heterocyclic, aryl, or heteroaryl ring;
• each instance of RC is independently selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —ORC1, —N(RC1)2, —SRC1, —CN, —C(═NRC1)RC1, —C(═NRC1)ORq, —C(═NRC1)SRC1, —C(═NRC1)N(RC1)2, —C(═O)RC1, —C(═S)RC1, —C(═S)ORC1, —C(═S)SRC1, —C(═S)N(RC1)2, —NO2, —N3, —N(RC1)3+F−, —N(RC1)3+Cl−, —N(RC1)3+Br−, —N(RC1)3+I−, —N(ORC1)RC1, —NRC1C(═O)RC1, —NRC1C(═O)ORC1, —NRC1C(═O)SRC1, —NRC1C(═O)N(RC1)2, —NRC1C(═S)RC1, —NRC1C(═S)ORC1, —NRC1C(═S)SRC1, —NRC1C(═S)N(RC1)2, —NRC1C(═NR)RC1, —NRC1C(═NRC1)ORC1, —NRC1C(═NRC1)SRC1, —NRC1C(═NRC1)N(RC1)2, —NRC1S(═O)2RC1, —NRC1S(═O)2ORC1, —NRC1S(═O)2SRC1, —NRC1S(═O)2N(RC1)2, —NRC1S(═O)RC1, —NRC1S(═O)ORC1, —NRC1S(═O)SRC1, —NRC1S(═O)N(RC1)2, —NRC1P(═O), —NRC1P(═O)2, —NRC1P(═O)(RC1)2, —NRC1P(═O)RC1(ORC1), —NRC1P(═O)(ORC1)2, —OC(═O)RC1, —OC(═O)ORC1, —OC(═O)SRC1, —OC(═O)N(RC1)2, —OC(═NRC1)RC1, —OC(═NRC1)ORC1, —OC(═NRC1)N(RC1)2, —OC(═S)RC1, —OC(═S)ORC1, —OC(═S)SRC1, —OC(═S)N(RC1)2, —ON(RC1)2, —OS(═O)RC1, —OS(═O)ORC1, —OS(═O)SRC1, —OS(═O)N(RC1)2, —OS(═O)2RC1, —OS(═O)2ORC1, —OS(═O)2SRC1, —OS(═O)2N(RC1)2, —OP(═O)2, —OP(═O)(RC1)2, —OP(═O)RC1(ORC1), —OP(═O)(ORC1)2, —OP(═O), —OP(RC1)2, —OPRC1(ORC1), —OP(ORC1)2, —OSi(RC1)3, —OSi(RC1)2ORC1, —OSi(RC1)(ORC1)2, —OSi(ORC1)3, —SSRC1, —S(═O)RC1, —S(═O)ORC1, —S(═O)N(RC1)2, —S(═O)2RC1, —S(═O)2ORC1, —S(═O)2N(RC1)2, —SC(═O)RC1, —SC(═O)ORC1, —SC(═O)SRC1, —SC(═O)N(RC1)2, —SC(═S)RC1, —SC(═S)ORC1, —SC(═S)SRC1, —SC(═S)N(RC1)2, —P(RC1)2, —PRC1(ORC1), —P(ORC1)2, —P(═O), —P(═O)(RC1)2, —P(═O)(ORC1)2, —P(═O)RC1(ORC1), —P(═O)2, —B(RC1)2, —B(ORC1)2, —BRC1(ORC1), —Si(RC1)3, —Si(RC1)2ORC1, —SiRC1(ORC1)2, and —Si(ORC1)3, wherein each occurrence of RC1 is independently selected from the group consisting of hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, a nitrogen protecting group when attached to a nitrogen atom, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, or two RC1 groups are joined to form an optionally substituted heterocyclic ring or optionally substituted heteroaryl ring;
• Rq is independently hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group;
• n is 0, 1, 2, 3, or 4;
• L is a bond or an optionally substituted, branched or unbranched C1-6 hydrocarbon chain;
• RD is any one of Formulae (i-1)-(i-43):
• wherein:
• each instance of RD1 is independently hydrogen, halogen, acyl, 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, —CN, —NO2, —ORD1a, —N(RD1a)2, —SRD1a, —CH2ORD1a, —CH2N(RD1a)2, —CH2SRD1a, —C(═O)RD1a, —C(═O)ORD1a, —C(═O)SRD1a, —C(═O)N(RD1a)2, —C(═S)RD1a, —C(═S)ORD1a, —C(═S)SRD1a, —C(═S)N(RD1a)2, —C(═NRD1a)RD1a, —C(═NRD1a)ORD1a C(═NRD1a)SRD1a, or —C(═NRD1a)N(RD1a)2, wherein each occurrence of RD1a is independently hydrogen, acyl, 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, or two RD1a groups are joined to form an substituted or unsubstituted heterocyclic ring;
• each instance of RD2 is independently hydrogen, halogen, acyl, 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, —CN, —NO2, —ORD2a, —N(RD2a)2, —SRD2a, —CH2ORD2aCH2N(RD2a)2, —CH2SRD2a, —C(═O)RD2a, —C(═O)ORD2a, —C(═O)SRD2a, —C(═O)N(RD2a)2, —C(═S)RD2a, —C(═S)ORD2a, —C(═S)SRD2a, —C(═S)N(RD2a)2, —C(═NRD2a)RD2a, —C(═NRD2a)ORD2a, —C(═NRD2a)SRD2a, and —C(═NRD2a)N(RD2a)2, wherein each occurrence of RD2a is independently hydrogen, acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl, or two RD2a groups are joined to form an substituted or unsubstituted heterocyclic ring;
• each instance of RD3 is independently hydrogen, halogen, acyl, 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, —ORD3a, —N(RD3a)2, —SRD3a, —CH2ORD3a, —CH2N(RD3a)2, —CH2SRD3a, —C(═O)RD3a, —C(═O)ORD3a, —C(═O)SRD3a, —C(═O)N(RD3a)2, —C(═S)RD3a, —C(═S)ORD3a, —C(═S)SRD3a, —C(═S)N(RD3a)2, —C(═NRD3a)RD3a, —C(═NRD3a)ORD3a, —C(═NRD3a)SRD3a, or —C(═NRD3a)N(RD3a)2 wherein each occurrence of RD3a is independently hydrogen, acyl, 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, or two RD3a groups are joined to form an substituted or unsubstituted heterocyclic ring;
• optionally RD1 and RD3, or RD2 and RD3, or RD1 and RD2 are joined to form an substituted or unsubstituted carbocyclic or substituted or unsubstituted heterocyclic ring;
• RD4 is a leaving group selected from the group consisting of —Br, —Cl, —I, and —OS(═O)wRD4a, wherein w is 1 or 2, and RD4a 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;
• each instance of X1 is independently a bond, —C(═O)—, —SO2—, —NRD5—, optionally substituted alkylene, or optionally substituted heteroarylene, wherein RD5 is hydrogen, C1-6 alkyl, or a nitrogen protecting group;
• each instance of Y is independently O, S, or NRD6, wherein RD6 is hydrogen, C1-6 alkyl, or a nitrogen protecting group;
• and
• each instance of z and z1 is independently 0, 1, 2, 3, 4, 5, or 6, as valency permits.