Amino Acid Refunctionalization

One method to generate cyclic amino acids is to begin with a cyclic precursor. Refunctionalization of the existing groups lead to the amino acid. 

There are a handful of examples where amino acids with ring sizes of seven members and larger have been prepared using the carboxyl refunctionalization reaction just shown. Reaction of anhydride 7.29H with ammonia, for example, gave amide-acid 7.30. Hofmann rearrangementl of the amide led to cfs-2-aminocyclo-heptane-1-carboxylic acid, 731. An alternative synthesis conjugate addition of ammonia to cycloheptenecarboxylic acid, 7.32. This reaction gave rra/is-2-amino-cycloheptane-1-carboxylic acid, 7.33. 

A lactone can be refunctionalized to an amino acid as well as a carboxylic acid. Reaction of 7.34 with potassium phthalimide opened the lactone ring to give a phthalimido-acid. Removal of the phthalimide group gave 2-methylamino-l-phenyl-cyclopropane-1-carboxylic acid, 7.35Amino acid 7.35 was tested as a potential antidepressant, and several aryl analogs were prepared the 4-chlorophenyl, the 4-methylphenyl, and the 4-methoxyphenyl derivatives. 

Lactams are cyclic molecules that can be used as synthetic precursors to cyclic amino acids, usually by refunctionalization reactions. One example is the conversion of the alkene moiety in bicyclic lactam 7.75 (2-azabicyclo[2.2.1]hepl-5-en-3-... 

Several syntheses have appeared in which pyrrolidine carboxylic acids other than proline have been prepared. Refunctionalization of proline is an also excellent route to "non-proline" amino acids, however, because of the ready availability of proline and its derivatives. Proline (7.250) was converted to aldehyde 7.25J by standard procedures, and Wittig olefination lej to 7.252.133 In an interesting transforma-... 

This monograph is divided into seven chapters. In the first chapter, methods for synthesizing the fundamental structural types found in acyclic amino acids are presented. In this chapter, the synthetic methods rely on substituent refunctionalization. In chapter two, refunctionalization again plays a prominent role. The major difference is that cyclic precursors are used to prepare acyclic amino acids. Chapter... 

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