176502-70-8

Upstream product

• 187526-99-4 (9H-fluoren-9-yl)methyl (S)-(1-(4-(tert-butoxy)phenyl)-3-hydroxypropan-2-yl)carbamate 
• 4727-00-8 O-t-Butyl-L-tyrosine 
• 60-18-4 L-tyrosine 
• 3417-91-2 L-tyrosine methyl ester HCl 
• 5545-54-0 N-(benzyloxycarbonyl)-O-(1,1-dimethylethyl)-L-tyrosine 
• 13512-31-7 N-(benzyloxycarbonyl)-L-tyrosine methyl ester 
• 5068-29-1 2-benzyloxycarbonylamino-3-(4-tert-butoxy-phenyl)-propionic acid methyl ester 
• 71989-38-3 Fmoc-Tyr(tBu)-OH 
• 109953-91-5 [1-(4-tert-butoxy-benzyl)-2-hydroxy-ethyl]-carbamic acid benzyl ester 

Downstream Products

• 109953-91-5 [1-(4-tert-butoxy-benzyl)-2-hydroxy-ethyl]-carbamic acid benzyl ester 
• 1200694-90-1 (S)-2-(4-tert-butoxybenzyl)aziridine 
• 1380230-91-0 (S)-2,5-dioxopyrrolidin-1-yl (2-azido-3-(4-(tert-butoxy)phenyl)propyl)carbamate 
• 869735-99-9 2-[2-azido-3-(4-tert-butoxy-phenyl)-propyl]-isoindole-1,3-dione 
• 1262483-67-9 C₂₉H₃₆N₈O₃*ClH 
• 1262483-65-7 C₂₉H₃₆N₈O₃*ClH 
• 1262483-62-4 C₃₈H₅₂N₈O₅ 
• 1262483-60-2 C₃₈H₅₂N₈O₅ 
• 220237-32-1 N^α-(Dde)-O-(4-methylphenoxy-allyl acetate)-L-tyrosinol 
• 220237-31-0 N^α-(Dde)-L-tyrosinol 
• 444884-81-5 [2-azido-3-(4-tert-butoxy-phenyl)-propoxy]-acetic acid tert-butyl ester 
• 880489-97-4 ethyl {[(2S)-2-azido-3-(4-tert-butoxyphenyl)propyl]oxy}acetate 

Relevant academic research and scientific papers

Microwave-enhanced solid-phase synthesis of N,N′-linked aliphatic oligoureas and related hybrids

A practical and efficient microwave-assisted solid-phase method for the synthesis of N,N′-linked oligoureas and related amide/urea hybrid oligomers, featuring the use of succinimidyl (2-azido-2-substituted ethyl) carbamate monomers, is reported. The rate enhancement of urea formation under microwave irradiation combined with the mild conditions of the phosphine-based azide reduction makes this approach very effective for routine synthesis of oligoureas and possibly for library production.

Universal peptidomimetics

This paper concerns peptidomimetic scaffolds that can present side chains in conformations resembling those of amino acids in secondary structures without incurring excessive entropic or enthalpic penalties. Compounds of this type are referred to here as minimalist mimics. The core hypothesis of this paper is that small sets of such scaffolds can be designed to analogue local pairs of amino acids (including noncontiguous ones) in any secondary structure; i.e., they are universal peptidomimetics. To illustrate this concept, we designed a set of four peptidomimetic scaffolds. Libraries based on them were made bearing side chains corresponding to many of the protein-derived amino acids. Modeling experiments were performed to give an indication of kinetic and thermodynamic accessibilities of conformations that can mimic secondary structures. Together, peptidomimetics based on these four scaffolds can adopt conformations that resemble almost any combination of local amino acid side chains in any secondary structure. Universal peptidomimetics of this kind are likely to be most useful in the design of libraries for high-throughput screening against diverse targets. Consequently, data arising from submission of these molecules to the NIH Molecular Libraries Small Molecule Repository (MLSMR) are outlined.

Synthesis of novel N-protected β3-amino nitriles: study of their hydrolysis involving a nitrilase-catalyzed step

Several commercially available nitrilases were investigated with regard to their potential to hydrolyze N-protected β3-amino nitriles into their corresponding N-protected β3-amino acids. The biotransformations were obtained in different proportions depending on the nitrilase involved. The best hydrolysis results were achieved for the N-Cbz-β3-amino nitrile from l-alanine using the NIT-107, in a phosphate buffer at 0.05 M. However, no biotransformation into the corresponding acids was observed for the N-sulfonylamide β3-amino nitriles. Two simple and efficient procedures to prepare the β3-amino nitriles from their analogous α-amino acids are described. Thirty four new substances were synthesized and characterized over the course of this work.

Synthesis and biological evaluation of leucine enkephalin turn mimetics

A cyclic Leu-enkephalin mimetic containing a 7-membered ring, and two linear analogues, has been prepared on solid phase. In the cyclic mimetic the intramolecular (1-4) hydrogen bond found in crystalline Leu-enkephalin has been replaced by an ethylene bridge. In addition, the amide bond between Tyr1 and Gly2 has been replaced by a methylene ether isostere and Gly3 has been deleted. The two linear analogues both contain the methylene ether isostere instead of the Tyr1-Gly2 amide bond and the shorter of the two lacks Gly3. The three compounds, and a β-turn mimetic analogous to the 7-membered turn mimetic but with Gly3 included, were evaluated for specific binding to μ- and δ-opioid receptors in rat brain membranes. With the exception of the β-turn mimetic the three other Leu-enkephalin analogues all bound with varying affinity to the μ- and δ-opioid receptors. From the results it could be concluded that Leu-enkephalin binds in a turn conformation to the opiate receptors, but that this conformation is not a (1-4) β-turn. The Royal Society of Chemistry 2006.

Syntheses of amino alcohols and chiral C2-symmetric bisoxazolines derived from O-alkylated R-4-hydroxyphenylglycine and S-tyrosine

Chiral C2-symmetric bisoxazolines 1b-f and 2b,c, derived from 4′-O-alkylated R-4-hydroxyphenylglycine or S-tyrosine, were prepared. As intermediates, a series of chiral amino alcohols possessing substituted phenolic groups was prepared and fully characterized.

Stereoselective synthesis of Ψ[CH2O] pseudodipeptides and conformational analysis of a PheΨ[CH2O]Ala containing analogue of the drug desmopressin

A method for the synthesis of XaaΨ[CH2O]Ala/Gly pseudodipeptides in good yields and excellent diastereoselectivity from azido alcohols and (R)-2-chloropropionic acid or tert-butyl bromoacetate has been developed. Insertion of one of the pseudodipeptide building blocks in the peptide drug desmopressin revealed that methylene either isosteres may have only a minor influence on the secondary structure of peptides.

Solid-phase synthesis of tyrosine peptide aldehydes. Analogues of (S)- MAPI

We report an efficient solid-phase synthesis of C-terminal tyrosine peptide aldehydes based on the HIV protease inhibitors (S)-MAPI and GE 20372 A. Our strategy consisted of anchoring the side chain of Dde-Tyrosinol (5) onto the brominated Wang linker derivative ((4-bromomethyl)-phenoxy-allyl acetate) (6) to give after ester hydrolysis the Na-(Dde)-O-(4- methylphenoxyacetic acid)-L-Tyrosinol template (8). This was attached to aminomethyl resin and elongated using standard Fmoc protocols. Importantly there was no evidence of esterification side reactions. The unsymmetrically substituted urea linkage of the (S)-MAPI family was incorporated using the Na-(4-nitrophenyloxycarbonyl)amino acid tert-butyl esters following which the protected tetrapeptide alcohol immobilized on the solid support was oxidized to its corresponding aldehyde using sulfur trioxide-pyridine. The efficiency and reliability of the oxidation step was dramatically improved by the incorporation of a small PEG-spacer between the linker and the solid support. The tetrapeptides 12a and 12b were cleaved by acidolysis, purified by RP HPLC, and isolated in high yield and purity, demonstrating the success of the whole synthetic process.