7670-20-4

Usage

Uses

Used in Pharmaceutical Industry:
Z-PHE-OTBU is used as a protecting group for phenylalanine in the synthesis of peptides for various pharmaceutical applications. It is crucial for preventing unwanted side reactions that could compromise the integrity and efficacy of the final peptide product.
Used in Research and Development:
In the field of research and development, Z-PHE-OTBU is utilized as a protecting agent in the synthesis of complex peptides and peptide-based therapeutics. Its selective removal under specific conditions allows for precise control over the synthesis process, facilitating the development of novel peptide-based drugs and other bioactive molecules.
Used in Biochemistry and Molecular Biology:
Z-PHE-OTBU is employed as a protecting group in biochemical and molecular biology research, where the synthesis of specific peptides is required for studying protein-protein interactions, enzyme substrate specificity, and other biological processes. Its ability to mask the reactive groups of phenylalanine ensures that the peptides are synthesized without unwanted modifications or degradation.
Used in Chemical Synthesis:
In the broader field of chemical synthesis, Z-PHE-OTBU is used as a protecting group for phenylalanine in the preparation of various organic compounds and materials. Its selective removal under specific conditions allows for the controlled synthesis of complex organic structures, including pharmaceuticals, agrochemicals, and other specialty chemicals.

Upstream product

• 558-17-8 tert-Butyl iodide 
• 1161-13-3 N-Cbz-L-Phe 
• 115-11-7 isobutene 
• 24424-99-5 di-tert-butyl dicarbonate 
• 19506-72-0 benzyl-8-quinolyl carbonate 
• 16874-17-2 L-phenylalanine tert-butyl ester 
• 30134-61-3 N-Benzyloxycarbonyl-benzylaziridinon 
• 75-65-0 tert-butyl alcohol 
• 98946-18-0 tert-Butyl 2,2,2-trichloroacetimidate 
• 118786-34-8 1,1-dimethylethyl 2-[[(phenylmethoxy)carbonyl]amino]-2-propenoate 
• 98-80-6 phenylboronic acid 
• 13139-17-8 N-(Benzyloxycarbonyloxy)succinimide 
• 501-53-1 benzyl chloroformate 
• 63-91-2 L-phenylalanine 

Downstream Products

• 1161-13-3 N-Cbz-L-Phe 
• 7669-70-7 Z-Glu(OBu-t)-Phe-OBu-t 
• 194724-09-9 (S)-1-Benzyl-2-tert-butoxy-ethylamine 
• 6695-43-8 (S)-tert-butyl 2-((S)-2-(((benzyloxy)carbonyl)amino)propanamido)-3-phenylpropanoate 
• 35909-92-3 N-carbobenzoxy-L-phenylalanine methyl ester 
• 28709-70-8 N-benzyloxycarbonyl-L-phenylalanine ethyl ester 
• 60379-01-3 N-(benzyloxycarbonyl)-L-phenylalanine benzyl ester 
• 1361051-52-6 Z-Sar-L-Phe-O(t-Bu) 
• 1246175-34-7 H-Sar-L-Phe-O(t-Bu)*HCl 
• 1313619-01-0 C₃₇H₅₅N₅O₉S 
• 1313618-97-1 C₃₇H₅₅N₅O₉S 
• 1313618-95-9 C₃₈H₅₇N₅O₉S 
• 1313619-20-3 C₂₈H₃₇N₅O₆S 
• 1313619-18-9 C₂₉H₃₉N₅O₆S 

Relevant academic research and scientific papers

Asymmetric Synthesis of Functionalized Phenylalanine Derivatives via Rh-Catalyzed Conjugate Addition and Enantioselective Protonation Cascade

The asymmetric conjugate addition of arylboronic acids to N-phthalimidodehydroalanine 1i catalyzed by Rh(I)/L1a enables the facile preparation of chiral functionalized phenylalanines. The reaction proceeds by a conjugate addition and enantioselective protonation cascade, affording a rhodium enolate that undergoes re-face protonation. The reaction tolerates various arylboronic acids and can be used in the gram-scale synthesis of (S)-phenylalanine hydrochloride, demonstrating the reaction scope and the synthetic feasibility of the process.

4-Biphenylalanine- and 3-Phenyltyrosine-Derived Hydroxamic Acids as Inhibitors of the JumonjiC-Domain-Containing Histone Demethylase KDM4A

Overexpression of the histone lysine demethylase KDM4A, which regulates H3K9 and H3K36 methylation states, has been related to the pathology of several human cancers. We found that a previously reported hydroxamate-based histone deacetylase (HDAC) inhibitor (SW55) was also able to weakly inhibit this demethylase with an IC50value of 25.4 μm. Herein we report the synthesis and biochemical evaluations, with two orthogonal in vitro assays, of a series of derivatives of this lead structure. With extensive chemical modifications on the lead structure, also by exploiting the versatility of the radical arylation with aryldiazonium salts, we were able to increase the potency of the derivatives against KDM4A to the low-micromolar range and, more importantly, to obtain demethylase selectivity with respect to HDACs. Cell-permeable derivatives clearly showed a demethylase-inhibition-dependent antiproliferative effect against HL-60 human promyelocytic leukemia cells.

Convenient and Simple Esterification in Continuous-Flow Systems using g-DMAP

The utility and applicability of polyethylene-g-polyacrylic acid-immobilized dimethylaminopyridine (g-DMAP) as a catalyst in a continuous-flow system were investigated for decarboxylative esterification. High catalytic activity toward acylation was provided by g-DMAP containing a flexible grafted-polymer structure. During decarboxylation, carboxylic acids and alcohols were converted cleanly using di-tert-butyl dicarbonate (Boc2O) as a coupling reagent, which reduced by-products. In addition, the use of Boc2O resulted in the formation of tert-butyl esters. These esterifications dramatically reduced the reaction time under continuous-flow conditions, with a residence time of approximately 2 min. This highly efficient esterification procedure will provide more practical industrial applications.

Solventless mechanosynthesis of N-protected amino esters

Mechanochemical derivatizations of N- or C-protected amino acids were performed in a ball mill under solvent-free conditions. A vibrational ball mill was used for the preparation of N-protected α- and β-amino esters starting from the corresponding N-unmasked precursors via a carbamoylation reaction in the presence of di-tert-butyl dicarbonate (Boc2O), benzyl chloroformate (Z-Cl) or 9-fluorenylmethoxycarbonyl chloroformate (Fmoc-Cl). A planetary ball mill proved to be more suitable for the synthesis of amino esters from N-protected amino acids via a one-pot activation/esterification reaction in the presence of various dialkyl dicarbonates or chloroformates. The spot-to-spot reactions were straightforward, leading to the final products in reduced reaction times with improved yields and simplified work-up procedures.

Toward the selective delivery of chemotherapeutics into tumor cells by targeting peptide transporters: Tailored gold-based anticancer peptidomimetics

Complexes [AuIIIX2(dtc-Sar-AA-O(t-Bu))] (AA = Gly, X = Br (1)/Cl (2); AA = Aib, X = Br (3)/Cl (4); AA = l-Phe, X = Br (5)/Cl (6)) were designed on purpose in order to obtain gold(III)-based anticancer peptidomimetics that might specifically target two peptide transporters (namely, PEPT1 and PEPT2) upregulated in several tumor cells. All the compounds were characterized by means of FT-IR and mono- and multidimensional NMR spectroscopy, and the crystal structure of [AuIIIBr2(dtc-Sar-Aib-O(t- Bu))] (3) was solved and refined. According to in vitro cytotoxicity studies, the Aib-containing complexes 3 and 4 turned out to be the most effective toward all the human tumor cell lines evaluated (PC3, DU145, 2008, C13, and L540), reporting IC50 values much lower than that of cisplatin. Remarkably, they showed no cross-resistance with cisplatin itself and were proved to inhibit tumor cell proliferation by inducing either apoptosis or late apoptosis/necrosis depending on the cell lines. Biological results are here reported and discussed in terms of the structure-activity relationship.

Asymmetric α-2-tosylethenylation of N,N-dialkyl-l-amino acid esters via the formation of non-racemic ammonium enolates

Asymmetric α-2-tosylethenylation of (S)-2-(pyrrolidin-1-yl)propanoic acid esters was shown to produce good yields with high enantioselectivities. The reaction proceeds via the formation of a non-racemic ammonium enolate without an external source of chirality.

Versatile selective α-carboxylic acid esterification of N-protected amino acids and peptides by alcalase

Under continuous removal of water, the industrial protease Alcalase allows selective synthesis of α-carboxylic acid methyl, ethyl, benzyl, allyl, 2-(trimethylsilyl)ethyl, and tert-butyl esters of amino acids and peptides under mild conditions in very high

Structure-activity study of endomorphin-2 analogs with C-terminal modifications by NMR spectroscopy and molecular modeling

Endomorphin-2 (EM-2) is a putative endogenous μ-opioid receptor ligand. To get insight into the important role of C-terminal amide group of EM-2, we investigated herein a series of EM-2 analogs by substitution of the C-terminal amide group with -NHNH2, -NHCH3, -N(CH3)2, -OCH3, -OCH2CH3, -OC(CH3)3, and -CH2-OH. Their binding affinity and bioactivity were determined and compared. Despite similar (analogs 1, 4, and 7) or decreased (analogs 2, 3,5, and 6) μ affinity in binding assays, all analogs showed low guinea pig ileum (GPI) and mouse vas deferens (MVD) potencies compared to their parent peptide. Interestingly, as for analogs 2 and 3 (a single and double N-methylation of C-terminal amide), the potency order with the Ki (μ) values was 2 > 3; for the C-terminal esterified analogs 4-6, the potency order with the Ki (μ) values was 4 > 5 > 6. Thus, we concluded that the steric hindrance of C-terminus might play an important role in opioid receptor affinity. We further investigated the conformational properties of these analogs by 1D and 2D 1H NMR spectroscopy and molecular modeling. Evaluating the ratios of cis- and trans-isomers, aromatic interactions, dihedral angles, and stereoscopic views of the most convergent conformers, we found that modifications at the C-terminal amide group of EM-2 affected these analog conformations markedly, therefore changed the opioid receptor affinity and in vitro bioactivity.

Deprotection of t-butyl esters of amino acid derivatives by nitric acid in dichloromethane

The extension of the deprotection procedure of t-butylated carboxyl function using HNO3 in CH2Cl2 to a number of appropriately selected N-Z- derivatives of natural amino acid esters was investigated. The method was found to work effectively with alanine, phenylalanine, serine and the dipeptide aspartame, but the reagent brought about a number of unwanted transformations with tyrosine, methionine and tryptophan. Suitable protection of functions present in the latter ones allowed selective ester dealkylation, but tyrosine underwent unavoidable fast preliminary ring nitration. 2000 Elsevier Science Ltd.

Backbone amide linker (BAL) strategy for solid-phase synthesis of C-terminal-modified and cyclic peptides

Peptide targets for synthesis are often desired with C-terminal end groups other than the more usual acid and amide functionalities. Relatively few routes exist for synthesis of C-terminal-modified peptides-including cyclic peptides - by either solution or solid-phase methods, and known routes are often limited in terms of ease and generality. We describe here a novel Backbone Amide Linker (BAL) approach, whereby the growing peptide is anchored through a backbone nitrogen; thus allowing considerable flexibility in management of the termini. Initial efforts on BAL have adapted the chemistry of the tris(alkoxy)benzylamide system exploited previously with PAL anchors. Aldehyde precursors to PAL, e.g. 5-(4-formyl-3,5-dimethoxyphenoxy)valeric acid, were reductively coupled to the α-amine of the prospective C-terminal amino acid, which was blocked as a tert-butyl, allyl, or methyl ester, or to the appropriately protected C-terminal-modified amino acid derivative. These reductive aminations were carried out either in solution or on the solid phase, and occurred without racemization. The secondary amine intermediates resulting from solution amination were converted to the 9-fluorenylmethoxycarbonyl (Fmoc)-protected preformed handle derivatives, which were then attached to poly(ethylene glycol)-polystyrene (PEG-PS) graft or copoly(styrene - 1% divinylbenzene) (PS) supports and used to assemble peptides by standard Fmoc solid-phase chemistry. Alternatively, BAL anchors formed by onresin reductive amination were applied directly. Conditions were optimized to achieve near-quantitative acylation at the difficult step to introduce the penultimate residue, and a side reaction involving diketopiperazine formation under some circumstances was prevented by a modified protocol for Nα-protection of the second residue/ introduction of the third residue. Examples are provided for the syntheses in high yields and purities of representative peptide acids, alcohols, N,N-dialkylamides, aldehydes, esters, and head-to-tail cyclic peptides. These methodologies avoid postsynthetic solution-phase transformations and are ripe for further extension.