185142-08-9Relevant academic research and scientific papers
Racemization in the use of N-(9-(9-phenylfluorenyl))serine-derived cyclic sulfamidates in the synthesis of delta-keto alpha-amino carboxylates and prolines.
Wei,Lubell
, p. 2595 - 2598 (2007/10/03)
[reaction: see text]Ring opening of enantiopure N-(9-(9-phenylfluorenyl)serine-derived cyclic sulfamidates with beta-keto esters, beta-keto ketones, and dimethyl malonate gave a variety of gamma-substituted amino acid analogues in racemic form. Investigat
5-tert-butylproline
Beausoleil,L'Archeveque,Belec,Atfani,Lubell
, p. 9447 - 9454 (2007/10/03)
Steric effects on the isomer equilibrium of amides N-terminal to proline can be explored with 5-alkylprolines having bulky 5-position substituents. Enantiopure 5-tert-butylprolines were thus synthesized from glutamic acid via an acylation/diastereoselective reductive amination sequence. Double deprotonation of γ-methyl N-(PhF)glutamate (2) with LiN(SiMe3)2 and C-acylation with pivaloyl chloride provided β-keto ester 3, which upon γ-ester hydrolysis and decarboxylation gave δ-oxo-α-[N-(PhF)amino]heptanoic acid (4). Syntheses of (2S,5R)- and (2R,5S)-N-(BOC)-5-tert-butylprolines ((2S,5R)-1 and (2R,5S)-1) were accomplished by catalytic hydrogenation of their respective (2S)- and (2R)-methyl δ-oxo-α-[N-(PhF)amino]heptanoates ((2S)-5a and (2R)-5a) in methanol with di-tert-butyl dicarbonate followed by chromatography and ester hydrolysis with potassium trimethylsilanolate. The 5-tert-butylproline cis-diastereomers were proven to be of >99% enantiomeric purity after their conversion to diastereomeric α-methylbenzylamides 10. Good diastereoselectivity in favor of the trans-diastereomer was observed when (2S,5S)-5-tert-butylproline was synthesized from (2S)-δ-oxo-α-[N-(PhF)amino]heptanoate ((2S)-4) by solvolysis of the PhF group in trifluoroacetic acid and subsequent reduction of 5-tert-butyl-Δ5-dehydroproline (11) with tetramethylammonium triacetoxyborohydride; however, imino acid 11 was shown to be configurationally labile and racemized under acidic conditions. 5-tert-Butyl-Δ5-dehydroproline N'-methylamide 15 was configurationally stable in acid, yet preliminary attempts to reduce 15 favored cis-diastereomer 16. Alternatively, enantiopure trans-diastereomer, (2R,5R)-methyl N-(BOC)-5-tert-butylprolinate (9) was prepared by epimerization of (2S,5R)-9. In summary, this synthetic methodology now provides access to all four enantiopure 5-tert-butylproline isomers from inexpensive L- and D-glutamate as chiral educts.
