Gamma amino acid building blocks

A method for preparing a compound of Formula III:

• wherein
• R1 is alkyl, cycloalkyl, aryl, heteroaryl, or heterocycle;
• wherein the alkyl, cycloalkyl, aryl, heteroaryl, or heterocycle of R1 is optionally substituted with one to five alkyl, alkoxy, fluoro, protected hydroxy, aryl, (aryl)alkyl, heteroaryl, heterocycle, cycloalkyl, alkanoyl, alkoxycarbonyl, protected amino, alkylamino, dialkylamino, acylamino, trifluoromethyl, trifluoromethoxy, carboxy, carboxyalkyl, keto, arylsulfonyl, cyano, or azide groups;
• A3 is carbon;
• A4 is carbon or nitrogen;
• A5 is carbon, or nitrogen provided that A6 is not a direct bond;
• A6 is carbon, or a direct bond;
• and
• each of A3-A6 are optionally substituted with one or two alkyl, alkoxy, halo, protected hydroxy, aryl, (aryl)alkyl, heteroaryl, heterocycle, cycloalkyl, alkanoyl, alkoxycarbonyl, protected amino, alkylamino, dialkylamino, acylamino, trifluoromethyl, trifluoromethoxy, carboxy, carboxyalkyl, keto, arylsulfonyl, cyano, or azide groups, or one nitrogen protecting group;
• or a salt or solvate thereof;
• comprising contacting:
• a compound of Formula IV:
• wherein R1 is as defined for Formula III;
• and
• a cyclic compound of 5 or 6 ring atoms that includes a nitroethylene moiety within the ring and that optionally includes one or two nitrogen atoms in the ring, wherein the carbon atoms in the ring are optionally substituted and the optional nitrogen atom or atoms in the ring are optionally substituted by a nitrogen protecting group;
• in the presence of an organic solvent and a proline derivative, for a period of time sufficient to provide the compound of Formula III.

A compound of Formula I:

• wherein
• R1 is alkyl, cycloalkyl, aryl, heteroaryl, or heterocycle;
• R2 is H, OH, an amino acid or peptide, or ORx wherein Rx is alkyl, cycloalkyl, aryl, heteroaryl, heterocycle, or an oxygen protecting group;
• Y is nitro, amino, a nitrogen bonded to an amino acid, —NHRy, or —N(Ry)2, wherein each Ry is independently alkyl, cycloalkyl, aryl, heteroaryl, heterocycle, or a nitrogen protecting group;
• Z is O, S, or H, and the dashed line to Z is an optionally present bond that is absent when Z is H;
• A3 is carbon;
• A4 is carbon;
• A5 is carbon;
• A6 is carbon or a direct bond;
• each of A3-A6 are optionally substituted with one or two alkyl, alkoxy, fluoro, optionally protected hydroxy, aryl, (aryl)alkyl, heteroaryl, heterocycle, cycloalkyl, alkanoyl, alkoxycarbonyl, optionally protected amino, optionally protected aminoalkyl, optionally protected alkylamino, dialkylamino, acylamino, trifluoromethyl, trifluoromethoxy, optionally protected carboxy, optionally protected carboxyalkyl, keto, arylsulfonyl, cyano, or azide groups;
• and
• wherein each alkyl, cycloalkyl, aryl, heteroaryl, or heterocycle of any R1, R2, Rx, or Ry is optionally substituted with one to five alkyl, alkoxy, fluoro, optionally protected hydroxy, aryl, (aryl)alkyl, heteroaryl, heterocycle, cycloalkyl, alkanoyl, alkoxycarbonyl, optionally protected amino, optionally protected aminoalkyl, optionally protected alkylamino, dialkylamino, alkylaminoalkyl, dialkylaminoalkyl, acylamino, trifluoromethyl, trifluoromethoxy, optionally protected carboxy, optionally protected carboxyalkyl, keto, arylsulfonyl, cyano, or azide groups;
• or a salt or solvate thereof.

A method for preparing a compound of Formula III:

• wherein
• R1 is alkyl, cycloalkyl, aryl, heteroaryl, or heterocycle;
• wherein the alkyl, cycloalkyl, aryl, heteroaryl, or heterocycle of R1 is optionally substituted with one to five alkyl, alkoxy, fluoro, protected hydroxy, aryl, (aryl)alkyl, heteroaryl, heterocycle, cycloalkyl, alkanoyl, alkoxycarbonyl, protected amino, alkylamino, dialkylamino, acylamino, trifluoromethyl, trifluoromethoxy, carboxy, carboxyalkyl, keto, arylsulfonyl, cyano, or azide groups;
• A3 is carbon;
• A4 is carbon;
• A5 is carbon;
• A6 is carbon, or a direct bond;
• and
• each of A3-A6 are optionally substituted with one or two alkyl, alkoxy, halo, protected hydroxy, aryl, (aryl)alkyl, heteroaryl, heterocycle, cycloalkyl, alkanoyl, alkoxycarbonyl, protected amino, alkylamino, dialkylamino, acylamino, trifluoromethyl, trifluoromethoxy, carboxy, carboxyalkyl, keto, arylsulfonyl, cyano, or azide groups;
• or a salt or solvate thereof;
• comprising contacting:
• a compound of Formula IV:
• wherein R1 is as defined for Formula III;
• and
• a cyclic compound of 5 or 6 ring atoms that includes a nitroethylene moiety within the ring, wherein the carbon atoms in the ring are optionally substituted;
• in the presence of an organic solvent and a proline derivative, for a period of time sufficient to provide the compound of Formula III.