119595-73-2Relevant academic research and scientific papers
Selective tert-butyl ester deprotection in the presence of acid labile protecting groups with use of ZnBr2
Kaul, Ramesh,Brouillette, Yann,Sajjadi, Zohreh,Hansford, Karl A.,Lubell, William D.
, p. 6131 - 6133 (2007/10/03)
Chemoselective hydrolysis of tert-butyl esters in the presence of other acid-labile groups has been explored by employing α-amino esters and ZnBr2 in DCM. Although N-Boc and N-trityl groups were found to the labile, PhF protected amines were compatible with these Lewis acid deprotection conditions such that a variety of N-(PhF)amino acids were prepared in good yields from their corresponding tert-butyl esters.
Rigid dipeptide mimetics: Efficient synthesis of enantiopure indolizidinone amino acids
Lombart, Henry-Georges,Lubell, William D.
, p. 9437 - 9446 (2007/10/03)
An effective means to synthesize indolizidinone amino acids has been developed and furnishes all possible stereoisomers of these conformationally rigid mimetics of peptide secondary structures. Inexpensive glutamic acid was employed as chiral educt in a Claisen condensation/reductive amination/lactam cyclization sequence that furnished stereoselectively azabicyclo[3.4.0]alkane amino acid 1. Enantiopure (3S,6S,9S)- and (3R,6R,9R)-2-oxo-3-N-(BOC)amino-1-azabicyclo[4.3.0]nonane-9-carboxylic acids ((3S,6S,9S)- and (3R,6R,9R)-1) were respectively synthesized from L- and D-N-(PhF)glutamates 2 (PhF = 9-(9-phenylfluorenyl)). Slow addition of sodium bis(trimethylsilyl)amide to 2 provided good to excellent yields of β-keto esters 3, which were subsequently hydrolyzed and decarboxylated to give symmetric α,ω-bis[N-(PhF)amino]azelate δ-ketones 5. Augmentation of hydrogen pressure increased diastereoselectivity in reductive aminations with 5 and afforded 5-alkylprolines 8 and 10. Lactam formation on exposure of 10 to triethylamine and N-protection with di-tert-butyl dicarbonate gave methyl-2-oxo-3-[N-(BOC)amino]-1-azabicyclo[4.3.0]nonane-9-carboxylate (12) which on C-terminal ester hydrolysis with hydroxide ion gave enantiopure [N-(BOC)amino]indolizidinone acid 1. Alternatively, hydride addition to ketone 5a gave symmetric α,ω-bis[N-(PhF)amino]azelate δ-alcohol 7a, which upon mesylation and intramolecular S(N)2 displacement by the PhF amine gave specifically cis-5-alkylproline 15 that was similarly converted to (3S,6S,9S)-1. In addition, epimerization of the C-9 stereocenter of (3S,6S,9S)-[N-(BOC)amino]indolizidinone methyl ester 12 with NaN(SiMe3)2 and ester hydrolysis gave (3S,6S,9R)-indolizidinone amino acid (3S,6S,9R)-1. By providing efficient methodology for synthesizing all of the possible stereoisomers of enantiopure indolizidinone amino acid 1, our route is specifically designed to enhance the general use of these peptide mimetics in the exploration of conformation-activity relationships of various biologically active peptides.
Synthesis of 4-Substituted Prolines as Conformationally Constrained Amino Acid Analogues
Koskinen, Ari M. P.,Rapoport, Henry
, p. 1859 - 1866 (2007/10/02)
Anionic substitution of N-(9-(9-phenylfluorenyl))-protected glutamic acid esters proceeds without loss of optical integrity to give 4-substituted glutamic acid derivatives.The 4-methyl, propyl, cyanomethyl, and phenyl analogues have thus been prepared.Pri
