Homophenylalanine derivatives

This approach has also been leveraged toward the construction of differentiated imidazolidinone and aminooxazoline structures. Tandem approaches toward allylic C—H amination and sequential arylation have been demonstrated to access functionalized oxazolidinones toward homophenylalanine derivatives directly from the linear alkenyl carbamate (Scheme 3.22)."°... 

In the mid to late 1980s, many research groups focused on methods and processes to prepare L-phenylalanine (Chapter 3). This was a direct result of the demand for the synthetic, artificial sweetener aspartame. One of the many routes studied was the use of phenylalanine dH (Scheme 19.4, R = C6H5CH2) with phenylpyruvate (PPA) as substrate.57-58 This enzyme from Bacillus sphaericus shows a broad substrate specificity and, thus, has been used to prepare a number of derivatives of L-phenylalanine.59 A phenylalanine dH isolated from a Rhodococcus strain M4 has been used to make L-homophenylalanine (.S )-2-amino-4-pheny I butanoic acid], a key, chiral component in many angiotensin-converting enzyme (ACE) inhibitors.40 More recently, that same phenylalanine dH has been used to synthesize a number of other unnatural amino acids (UAAs) that do not contain an aromatic sidechain.43... 

The synthesis of the angiotensin-converting enzyme (ACE) inhibitor enalapril (1) incorporates the natural amino acids L-alanine and L-proline [1,2]. Although the compound can be thought of as a derivative of homophenylalanine, this part of the compound is prepared by a reductive amination with the keto ester (2), while the amino acids are coupled through an A-carboxy anhydride 3 (Scheme 1) [3-7]. 

The Petasis method involves the use of organoboron compounds to produce a side chain on a Mannich product derived from the imine condensation product between an amine and an a-ketocarboxylic acid. Thus, as shown in Scheme 12.64, as an example of this three-component reaction, when the styrylboronic acid derived from the reaction of phenylacetylene with catecholborane was allowed to react with glyoxylic acid (CHOCO2H) and (5)-2-phenylglycinol, a single diastereomer was isolated, which gave an enantiomerically pure (7 )-homophenylalanine hydrochloride on reduction. This procedure is limited only by the availability of the components. 

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