33900-15-1

Usage

Uses

Used in Pharmaceutical Industry:
L-Phenylalaninamide, N-[(1,1-dimethylethoxy)carbonyl]-L-leucylis used as an intermediate in the synthesis of γ-Secretase Inhibitors for the development of Alzheimer's disease treatments. The application reason is that these inhibitors can potentially reduce the formation of amyloid β-peptide (Aβ), which is a major causative agent in the progression of Alzheimer's disease. By targeting the enzyme complex responsible for Aβ generation, L-Phenylalaninamide, N-[(1,1-dimethylethoxy)carbonyl]-L-leucyl- plays a crucial role in the development of therapeutic strategies against AD.

Upstream product

• 5241-58-7 L-Phenylalanine amide 
• 33900-00-4 (S)-2-tert-Butoxycarbonylamino-4-methyl-pentanoic acid pyridin-2-yl ester 
• 3392-09-4 Boc-Leu-ONSu 
• 65864-22-4 (S)-2-amino-3-phenylpropionamide hydrochloride 
• 13139-15-6 N-tert-butoxycarbonyl-L-leucine 
• 63096-02-6 N-tert-butoxycarbonyl-L-leucine methyl ester 
• 88463-18-7 (S)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropionamide 
• 63-91-2 L-phenylalanine 
• 13734-34-4 N-tert-butoxycarbonyl-L-phenylalanine 

Downstream Products

• 38678-60-3 leucylphenylalanylamide 
• 74214-38-3 L-leucyl-L-phenylalaninamide hydrochloride 
• 294675-33-5 Boc-Leu-gPhe-COOMe 
• 109064-97-3 <4(S)-amino-2,2-difluoro-3(R)-hydroxy-6-methylheptanoyl>-L-leucyl-L-phenylalaninamide trifluoroacetate 
• 109064-95-1 <4(S)--2,2-difluoro-3(R)-hydroxy-6-methylheptanoyl>-L-leucyl-L-phenylalaninamide 
• 109121-33-7 <4(S)--2,2-difluoro-3(R)-hydroxy-6-methyheptanoyl>-L-leucyl-L-phenylalaninamide 
• 87063-27-2 Boc-Phe-His-Sta-Leu-Phe-NH₂ 
• 98168-94-6 His-Sta-Leu-Phe-NH₂*2HCl 
• 87063-45-4 Ac-Phe-His-Sta-Leu-Phe-NH₂ 
• 93962-09-5 (phenoxyacetyl)-His-Sta-Leu-Phe-NH₂ 
• 93962-08-4 Boc-His-Sta-Leu-Phe-NH₂ 
• 292620-20-3 (1S,4R)-{1-benzyl-4-[1-(1S)-carbamoyl-(2-phenylethylcarbamoyl)-(1S)-3-methylbutylcarbamoyl]-2-oxo-5-phenylpentyl}carbamic acid tert-butyl ester 
• 338801-69-7 {(1S,2R,4R)-1-Benzyl-2-(tert-butyl-dimethyl-silanyloxy)-4-[(S)-1-((S)-1-carbamoyl-2-phenyl-ethylcarbamoyl)-3-methyl-butylcarbamoyl]-5-phenyl-pentyl}-carbamic acid tert-butyl ester 
• 292632-98-5 (5S)-(tert-butoxycarbonylamino)-6-phenyl-(4R)-hydroxy-(2R)-benzylhexanoyl-L-leucy-L-phenylalaninamide 

Relevant academic research and scientific papers

Allyltrichlorostannane additions to α-amino aldehydes: Application to the total synthesis of the aspartyl protease inhibitors L-682,679, L-684,414, L-685,434, and L-685,458

The hydroxyethylene dipeptide isosteres L-682,679, L-684,414, L-685,434, and L-685,458 were synthesized in a few steps by a sequence involving an allyltrichlorostannane coupling with an α-amino aldehyde, followed by hydroboration of the corresponding 1,2-

Short total synthesis of aspartyl protease inhibitors L-685,434, L-682,679 and L-685,458

Hydroxyethylene dipeptide isosteres L-685,434, L-682,679 and L-685,458 were synthesized in a few steps by a sequence involving an allyltrichlorostannane coupling with an α-aminoaldehyde followed by hydroboration of the corresponding 1,2-syn and 1,2-anti a

Design and synthesis of HIV protease inhibitors. Variations of the carboxy terminus of the HIV protease inhibitor L-682,679

A series of tetrapeptide analogues of 1 (L-682,679), in which the carboxy terminus has been shortened and modified, was prepared and their inhibitory activity measured against the HIV protease in a peptide cleavage assay. Selected examples were tested as inhibitors of virus spread in cell culture. Compound 12 was a 10-fold more potent enzyme inhibitor than 1 in vitro and 30-fold more potent in inhibiting the viral spread in cells.

Enzymes in organic synthesis: Use of subtilisin and a highly stable mutant derived from multiple site-specific mutations

A subtilisin mutant (subtilisin 8350) derived from subtilisin BPN' via six-specific mutations (Met50Phe, Gly169Ala, Asn76Asp, Gln206Cys, Tyr217Lys, and Asn218Ser) was found to be 100 times more stable than the wild-type enzyme in aqueous solution at room temperature and 50 times more stable than the wild type in anhydrous dimethylformamide. Kinetic studies using ester, thio ester, and amide substrates, and the transition-state analogue inhibitor Boc-Ala-Val-Phe-CF3, indicate the both the wild-type and the mutant enzymes have very similar specificities and catalytic properties. The inhibition constant (K(i)) = 5.0 μM) for the wild-type enzyme is approximately 5 times that of the mutant enzyme (K(i)) = 1.1 μM), suggesting that the mutant enzyme binds the reaction transition state more strongly than the wild-type enzyme. This result is consistent with the observed rate constants for the corresponding ester and amide substrates; i.e. the k(cat)/k(m) values for the mutant are larger than those for hhe wild-type enzyme. Application of the mutant enzyme and the wild-type enzyme to organic synthesis has been demonstrated in the regioselective acylation of nucleosides in anhydrous dimethylformamide (with 65-100% regioselectivity at the 5'-position), in the enantioselective hydrolysis of N-protected and unprotected common and uncommon amino acid esters in water (with 85-98% enantioselectivity for the L-isomer), and in the synthesis of di- and oligopeptides via aminolysis of N-protected amino acid and peptide esters. The enzymatic peptide synthesis was carried out under high concentrations of DMF (~50%) to improve substrate solubility and to minimize enzymatic peptide cleavage. Low enantioselectivity was observed in the enzymatic transformation of non-amino acid alcohols and acids.

Renin Inhibitors. Syntheses of Subnanomolar, Competitive, Transition-State Analogue Inhibitors Containing a Novel Analogue of Statine

Analogues of the renin octapeptide substrate were synthesized in which replacement of the scissile dipeptide with (3S,4S)-4-amino-3-hydroxy-6-methylheptanoic acid (statine, Sta) transformed the substrate sequence into potent, transition-state analogue, competitive inhibitors of renin.Synthesis and incorporation of the cyclohexylalanyl analogue of Sta, (3s,4S)-4-amino-5-cyclohexyl-3-hydroxypentanoic acid (ACHPA), gave the most potent inhibitors of renin yet reported, including N-isovaleryl-L-histydyl-L-prolyl-L-phenylalanyl-L-histydyl-ACHPA-L-leucyl-L-phenylalanyl amide , with renin inhibitions of Ki=1.6 * 10-10 M (human kidney renin), IC50=1.7 * 10-10 M (human plasma renin), IC50=1.9 * 10-9 M (dog plasma renin), and IC50=2.1 * 10-8 M (rat plasma renin).This inhibitor 3, containing ACHPA, was 55-76 times more potent vs. human renin than the comparable Sta-containing inhibitor 1 and 17 times more potent vs. dog renin than 1.Inhibitor 3 lowered blood pressure in sodium-deficient dogs, with in vivo potency 19 times that shown by 1, in close agreement with the relative in vitro potencies.Structure-activity results are presented that show the minimal N-terminus for these inhibitors.An ACHPA-containing pentapeptide, N--L-phenylalanyl-L-histydyl-ACHPA-L-lecyl-L-phenylalanyl amide , retained subnanomolar inhibitory potency.Molecular modelling studies are described that suggested the design of ACHPA.