327052-53-9

Upstream product

• 56-41-7 L-alanin 
• 53934-78-4 (S)-2-amino-2-phenylacetic acid tert-butyl ester 
• 2935-35-5 (S)-2-phenylglycine 
• 860013-16-7 N-(N-carbobenzyloxy-L-alanyl)-(2S)-2-phenylglycine tert-butyl ester 

Downstream Products

• 208255-80-5 ((S)-tert-butyl 2-((S)-2-(2-(3,5-difluorophenyl)acetamido)propanamido)-2-phenylacetate) 
• 263162-50-1 (2S)-({N-[(3,5-difluorophenyl)acetyl]-L-alanyl}amino)(phenyl)acetic acid 
• 867022-09-1 6-[(S)-2-((S)-2-tert-Butoxycarbonylamino-propionylamino)-2-phenyl-acetylamino]-hexanoic acid (S)-2-((R)-3,4-bis-benzyloxy-5-oxo-2,5-dihydro-furan-2-yl)-2-hydroxy-ethyl ester 
• 867021-96-3 N-[N-(tert-butyloxycarbonyl)-L-alanyl]-(2S)-2-phenylglycine 

Relevant academic research and scientific papers

Peptide Bond Formation of Amino Acids by Transient Masking with Silylating Reagents

A one-pot peptide bond-forming reaction has been developed using unprotected amino acids and peptides. Two different silylating reagents, HSi[OCH(CF3)2]3 and MTBSTFA, are instrumental for the successful implementation of this approach, being used for the activation and transient masking of unprotected amino acids and peptides at C-termini and N-termini, respectively. Furthermore, CsF and imidazole are used as catalysts, activating HSi[OCH(CF3)2]3 and also accelerating chemoselective silylation. This method is versatile as it tolerates side chains that bear a range of functional groups, while providing up to >99% yields of corresponding peptides without any racemization or polymerization.

A surprising mechanistic "switch" in Lewis acid activation: A bifunctional, asymmetric approach to α-hydroxy acid derivatives

We report a detailed synthetic and mechanistic study of an unusual bifunctional, sequential hetero-Diels-Alder/ring-opening reaction in which chiral, metal complexed ketene enolates react with o-quinones to afford highly enantioenriched, α-hydroxylated carbonyl derivatives in excellent yield. A number of Lewis acids were screened in tandem with cinchona alkaloid derivatives; surprisingly, trans-(Ph3P)2PdCl2 was found to afford the most dramatic increase in yield and rate of reaction. A series of Lewis acid binding motifs were explored through molecular modeling, as well as IR, UV, and NMR spectroscopy. Our observations document a fundamental mechanistic "switch", namely the formation of a tandem Lewis base/Lewis acid activated metal enolate in preference to a metal-coordinated quinone species (as observed in other reactions of o-quinone derivatives). This new method was applied to the syntheses of several pharmaceutical targets, each of which was obtained in high yield and enantioselectivity.

Design of β-secretase inhibitors by introduction of a mandelyl moiety in DAPT analogues

We report the synthesis of two series of compounds with 3,5-difluoromandelyl-alanyl or 3,5-difluorophenylacetylalany1 backbones coupled to various heterocyclic or peptidic moieties. These two series of compounds were evaluated for their inhibitory propert

Enhanced delivery of γ-secretase inhibitor DAPT into the brain via an ascorbic acid mediated strategy

Inhibition of γ-secretase, one of the enzymes responsible for the cleavage of the amyloid precursor protein (APP) to produce pathogenic Aβ peptides, is an attractive approach for the treatment of Alzheimer's disease. We designed a γ-secretase inhibitor bearing an ascorbic acid moiety which allows a specific delivery of the drug to the brain. Through, on the one hand, Aβ peptide production measurements by specific in vitro assays (γ-secretase cell free assay and cell based assay on HEK 293 APP transfected cells) and on the other hand through pharmacokinetic studies on animal models, the new inhibitor shows a good pharmacokinetic profile as well as a potent γ-secretase inhibitory activity In vitro. From the obtained results, it is expected that drug 2 will be mainly delivered to the CNS with a low diffusion in the peripheral tissues. Consequently the side effects of this γ-secretase inhibitor on the immune cells could be reduced. The Royal Society of Chemistry 2005.

Parallel synthesis of DAPT derivatives and their γ-secretase- inhibitory activity

Parallel synthesis of the C-terminal-modified DAPT (1) derivatives was accomplished utilizing our novel resin 7. Condensation reaction of the N-acylamino acid 10 with the amines 11a-o proceeded smoothly to give the corresponding amides 6a-o without any epimerization. Among the analogues, the benzophenonemethyl amide derivative 6o showed 30 times more potent activity than the original DAPT (1).