Addition of Chiral Glycine, Methionine, and Vinylglycine Enolate Derivatives to Aldehydes and Ketones in the Preparation of Enantiomerically Pure α‐Amino‐β‐Hydroxy Acids

Abstract

Chiral enolates of imidazolidinones and oxazolidinones from the title amino acids react with carbonyl compounds to afford the corresponding alcohols in excellent yields (see Scheme 5). Furthermore, the addition to aldehydes proceeds with high diastereoselectivity to give, after acid hydrolysis, threo‐α‐amino‐β‐hydroxy acids of high enantiomeric purity. Some of the threo‐α‐amino‐β‐hydroxy acids prepared in this work are the proteinogenic (S)‐threonine (26), the naturally occurring (S)‐3‐phenylserine (28), and (S)‐3‐hydroxyleucine (27) as well as the unnatural (S)‐4,4,4‐trifluorothreonine (30) and (S)‐3‐(4‐pyridyl)serine (31). The N‐methylamide of (2S,3R,4R,6E)‐3‐hydroxy‐4‐methyl‐2‐(methylamino)‐6‐octenoic acid (32), the unique amino acid in the immunosuppressive cyclosporine, was prepared by the new method. This report presents also information suggesting that both steric and stereoelectronic effects are responsible for the good stereoselectivities observed.

Synthesis of Unnatural/Nonproteinogenic α‐Amino Acids

“…In some cases, the additional functionality in the side-chain may be desired, as in the example with an Evans oxazolidinone (Scheme 12.5) [16,17]. An amino acid can be used as the origin of stereochemistry and still reacted as in the concept of the regeneration of stereogenic centers (Scheme 12.6) [18][19][20]. The side-chain, R, can also be an alkene, which allows for conjugate additions or reductions to provide an unnatural amino acid; the stereochemical outcome is controlled by the tert-butyl group [19,21].…”

“…The side-chain, R, can also be an alkene, which allows for conjugate additions or reductions to provide an unnatural amino acid; the stereochemical outcome is controlled by the tert-butyl group [19,21]. The concept can be applied to glycine derivatives, although the enantiomers of the imidazidinone 6 (R ¼ H) need to be separated to achieve an enantioselective synthesis [18].…”

Preparation of (2R,3S)-β-hydroxy-α-amino acids by use of a novel Streptomyces aldolase as a resolving agent for racemic material

“…(b) Optically activeJ-hydroxy-or-amino acids serving a s reference compounds The compounds (2S,3R)-and (2R,3S)-3-(4-hydroxyphenyl)serine, 1 and 3, respectively, were synthesized by adaption of a published procedure (9). This involved condensing the (R) isomer of the glycine equivalent 10, or its enantiomer, with 4-benzyloxybenzaldehyde.…”

“…Hydrolysis of the product 11 obtained from 10 afforded the amino acid 3; the isomer 1 was obtained similarly from the enantiomer of 10. The corresponding 3-phenylserines 2 and 4 were obtained as previously reported (9). The imidazolidinone 10 and its enantiomer were obtained from Fluka Chemicals.…”

“…We have found one of these methods to have particular value (9) and have used it for the synthesis of (2S,3R)-and (2R,3S)-3-(4-hydroxyphenyl)serine, 1 and 3, respectively, and (2S,3R)-and (2R,3S)-3-phenylserine, 2 and 4, respectively (10); we have used these compounds here as reference materials.…”