Antibacterial cyclic lipopeptides

A cyclic peptide having Formula III:

• R1-R11 is the side chain of any amino acid, natural or unnatural, wherein R2 is not aspartic acid;
• R′ is H or methyl;
• R″ is H or methyl or ethyl
• R′″ is H or alkyl;
• R″″ is acyl or alkyl;
• X is O or NH;
• R is C5-C12 lipid or 4-phenylethynyl-phenyl of Formula II (Y is the substituent at any position of the aromatic ring)
• and
• Y is H, or an alkyl, or aryl or alkenyl, or alkynyl, or carbonyl, or heteroalkyl, or heteroaryl, or heterocycle, or hydroxyl, or halogen, or nitro group;
• wherein R′″ and R′″″ are not simultaneously H and —C(═O)H, respectively.

A cyclic peptide having Formula III:

• R1 is the side chain of Trp, N-alkylated Trp, or substituted 1- or 2-naphtylalanine;
• R2-R11 is the side chain of any amino acid, natural or unnatural, wherein R2 is not aspartic acid;
• R′ is H or methyl;
• R″ is H or methyl or ethyl
• R′″ is H or alkyl;
• R″″ is acyl or alkyl;
• X is O or NH;
• R is C5-C12 lipid or 4-phenylethynyl-phenyl of Formula II (Y is the substituent at any position of the aromatic ring))
• and
• Y is H, or an alkyl, or aryl or alkenyl, or alkynyl, or carbonyl, or heteroalkyl, or heteroaryl, or heterocycle, or hydroxyl, or halogen, or nitro group;
• wherein R′″ and R″″ are not simultaneously H and —C(═O)H, respectively.

A cyclic peptide resembling daptomycin analogue for Formula IV:

• R1 is the side chain of Trp, N-alkylated Trp, or substituted 1- or 2-naphthylalanine;
• R2 is H or methyl;
• R3 is the side chain of amino acid, natural or unnatural;
• R4 is H or methyl or ethyl;
• R5 is H or alkyl;
• R6 is acyl or alkyl;
• X is O or NH;
• R is C5-C12 lipid or 4-phenylethynyl-phenyl of Formula II (Y is the substituent at any position of the aromatic ring)
• and
• Y is H, or an alkyl, or aryl or alkenyl, or alkynyl, or carbonyl, or heteroalkyl, or heteroaryl, or heterocycle, or hydroxyl, or halogen, or nitro group;
• wherein R5 and R6 are not simultaneously H and —C(═O)H, respectively.

A cyclic lipopeptide having Formula V:

• R1-R12 is the side chain of any amino acid, natural or unnatural;
• R′ is H or methyl;
• R″ is H or methyl or ethyl;
• X is O or NH;
• Y is H, or an alkyl, or aryl or alkenyl, or alkynyl, or carbonyl, or heteroalkyl, or heteroaryl, or heterocycle, or hydroxyl, or halogen, or nitro group;
• Y′ is H, or an alkyl, or aryl or alkenyl, or alkynyl, or carbonyl, or heteroalkyl, or heteroaryl, or heterocycle, or hydroxyl, or halogen, or nitro group.

A cyclic lipopeptide having Formula I:

• R′ is alkyl, or aryl
• R1 is the side chain of Trp, N-alkylated Trp, or substituted 1- or 2-naphthylalanine;
• R2-R12 is the side chain of any amino acid, natural or unnatural;
• R″ is H or methyl or ethyl;
• X is O or NH;
• R is C5-C12 lipid or 4-phenylethynyl-phenyl of Formula II (Y is the substituent at any position of the aromatic ring)
• and
• Y is H, or an alkyl, or aryl or alkenyl, or alkynyl, or carbonyl, or heteroalkyl, or heteroaryl, or heterocycle, or hydroxyl, or halogen, or nitro group.