192057-94-6

Upstream product

• 30992-29-1 Boc-Aib-OH 
• 2577-90-4 methyl (2S)-2-amino-3-phenylpropanoate 
• 196214-22-9 (S)-methyl 2-(2,4-dinitrophenylsulfonamido)-3-phenylpropanoate 
• 7524-50-7 methyl (2S)-2-amino-3-phenylpropanoate hydrochloride 
• 1428047-03-3 C₁₁H₁₃NO₂S₂ 
• 51987-73-6 (S)-2-tert-butoxycarbonylamino-3-phenyl-propionic acid methyl ester 
• 13734-34-4 N-tert-butoxycarbonyl-L-phenylalanine 

Downstream Products

• 1242024-17-4 TFA*NH₂-Aib-L-Phe-OMe 
• 1287776-50-4 Boc-Aib-CSNH-L-Phe-OMe 
• 1287776-40-2 Boc-L-(?-Me)-His-D-Pro-Aib-CSNH-L-Phe-OMe 
• 104849-05-0 cyclo[2-aminoisobutyryl-(S)-phenylalanyl-(R)-prolyl-(S)-2-aminosuberoyl-] 
• 52574-63-7 (5S,11S,13aR)-5-Benzyl-8,8-dimethyl-11-(6-oxo-oct-7-enyl)-decahydro-3a,6,9,12-tetraaza-cyclopentacyclododecene-4,7,10,13-tetraone 
• 53342-16-8 chlamydocin 
• 88643-73-6 chlamydocin 
• 88643-73-6 epi-chlamydocin 
• 88568-96-1 Methyl N-(dimethylglycyl)-(S)-phenylalanyl-(R)-prolinate 
• 104848-99-9 N-Boc-Aib-(S)-Phe-(R)-Pro-OMe 

Relevant academic research and scientific papers

The unique crystallographic signature of a β-turn mimic nucleated by N-methylated phenylalanine and Aib as corner residue: Conformational and self-assembly studies

The secondary α-amino acid, proline, having high β-turn forming propensity is known to stabilize discrete conformations in peptides. A similar influence is ascribed to N-methylated amino acids with the advantage of the introduction of a side chain functio

Peptide-Catalyzed Fragment Couplings that Form Axially Chiral Non-C2-Symmetric Biaryls

We have demonstrated that small, modular, tetrameric peptides featuring the Lewis-basic residue β-dimethylaminoalanine (Dmaa) are capable of atroposelectively coupling naphthols and ester-bearing quinones to yield non-C2-symmetric BINOL-type scaffolds with good yields and enantioselectivity. The study culminates in the asymmetric synthesis of backbone-substituted scaffolds similar to 3,3′-disubstituted BINOLs, such as (R)-TRIP, with good (94:6 e.r.) to excellent (>99.9:0.1 e.r.) enantioselectivity after recrystallization, and a diastereoselective net arylation of the minimally modified nonsteroidal anti-inflammatory drug (NSAID) naproxen.

Divergent Access to Histone Deacetylase Inhibitory Cyclopeptides via a Late-Stage Cyclopropane Ring Cleavage Strategy. Short Synthesis of Chlamydocin

A unified step-economical strategy for accessing histone deacetylase inhibitory peptides is proposed, based on the late-stage installation of multiple zinc-binding functionalities via the cleavage of the strained cyclopropane ring in the common pluripoten

Pd-Catalyzed Site-Selective C(sp2)-H Olefination and Alkynylation of Phenylalanine Residues in Peptides

Pd-catalyzed site-selective C(sp2)-H olefination and alkynylation of phenylalanine residues in peptides are described. The amino acids within the peptides are used as native bidentate directing groups to facilitate C-H functionalization. This p

Diversity of Secondary Structure in Catalytic Peptides with β-Turn-Biased Sequences

X-ray crystallography has been applied to the structural analysis of a series of tetrapeptides that were previously assessed for catalytic activity in an atroposelective bromination reaction. Common to the series is a central Pro-Xaa sequence, where Pro is either l- or d-proline, which was chosen to favor nucleation of canonical β-turn secondary structures. Crystallographic analysis of 35 different peptide sequences revealed a range of conformational states. The observed differences appear not only in cases where the Pro-Xaa loop-region is altered, but also when seemingly subtle alterations to the flanking residues are introduced. In many instances, distinct conformers of the same sequence were observed, either as symmetry-independent molecules within the same unit cell or as polymorphs. Computational studies using DFT provided additional insight into the analysis of solid-state structural features. Select X-ray crystal structures were compared to the corresponding solution structures derived from measured proton chemical shifts, 3J-values, and 1H-1H-NOESY contacts. hese findings imply that the conformational space available to simple peptide-based catalysts is more diverse than precedent might suggest. The direct observation of multiple ground state conformations for peptides of this family, as well as the dynamic processes associated with conformational equilibria, underscore not only the challenge of designing peptide-based catalysts, but also the difficulty in predicting their accessible transition states. These findings implicate the advantages of low-barrier interconversions between conformations of peptide-based catalysts for multistep, enantioselective reactions.

Structural studies of β-turn-containing peptide catalysts for atroposelective quinazolinone bromination

We describe herein a crystallographic and NMR study of the secondary structural attributes of a β-turn-containing tetra-peptide, Boc-Dmaa-d-Pro-Acpc-Leu-NMe2, which was recently reported as a highly effective catalyst in the atroposelective bromination of 3-arylquinazolin-4(3H)-ones. Inquiries pertaining to the functional consequences of residue substitutions led to the discovery of a more selective catalyst, Boc-Dmaa-d-Pro-Acpc-Leu-OMe, the structure of which was also explored. This new lead catalyst was found to exhibit a type I′ β-turn secondary structure both in the solid state and in solution, a structure that was shown to be an accessible conformation of the previously reported catalyst, as well.

Enantioselective Synthesis of 3-Arylquinazolin-4(3H)-ones via Peptide-Catalyzed Atroposelective Bromination

We report the development of a tertiary amine-containing β-turn peptide that catalyzes the atroposelective bromination of pharmaceutically relevant 3-arylquinazolin-4(3H)-ones (quinazolinones) with high levels of enantioinduction over a broad substrate scope. The structure of the free catalyst and the peptide-substrate complex were explored using X-ray crystallography and 2D-NOESY experiments. Quinazolinone rotational barriers about the chiral anilide axis were also studied using density functional theory calculations and are discussed in light of the high enantioselectivities observed. Mechanistic studies also suggest that the initial bromination event is stereodetermining, and the major monobromide intermediate is an atropisomerically stable, mono-ortho-substituted isomer. The observation of stereoisomerically stable monobromides stimulated the conversion of the tribromide products to other atropisomerically defined products of interest. For example, (1) a dehalogenation Suzuki-Miyaura cross-coupling sequence delivers ortho-arylated derivatives, and (2) a regioselective Buchwald-Hartwig amination procedure installs para-amine functionality. Stereochemical information was retained during these subsequent transformations.

Synthesis of highly substituted imidazolidine-2,4-dione (Hydantoin) through Tf2O-mediated dual activation of Boc-protected dipeptidyl compounds

Highly substituted chiral hydantoins were readily synthesized from simple dipeptides in a single step under mild conditions. This reaction proceeded through the dual activation of an amide and a tert-butyloxycarbonyl (Boc) protecting group by Tf2O-pyridine. This method was successfully applied in the preparation of a variety of biologically active compounds, including drug analogs and natural products.

A traceless approach to amide and peptide construction from thioacids and dithiocarbamate-terminal amines

A novel and traceless strategy has been devised that allows a coupling of thioacids and dithiocarbamate-terminal amines. This strategy had been assumed to be dependent on the attachment of a functional equivalent of a cysteine side chain in earlier native chemical ligation approaches. This approach enables the traceless removal of CS2 to directly generate the desired amide bond and is compatible with a range of unprotected side chains of amino acid. The ability to produce amide or peptides by a traceless removal of the auxiliary is a significant virtue of the method. Meanwhile, the application of this new peptide-bond-forming reaction to the synthesis of novel endomorphin (EM) derivatives with various binding potencies was realized.

Enantioselective synthesis of atropisomeric benzamides through peptide-catalyzed bromination

We report the enantioselective synthesis of atropisomeric benzamides employing catalytic electrophilic aromatic substitution reactions involving bromination. The catalyst is a simple tetrapeptide bearing a tertiary amine that may function as a Br?nsted base. A series of tri- and dibrominations were accomplished for a range of compounds bearing differential substitution patterns. Tertiary benzamides represent appropriate substrates for the reaction since they exhibit sufficiently high barriers to racemization after ortho functionalization. Mechanism-driven experiments provided some insight into the basis for selectivity. Examination of the observed products at low conversion suggested that the initial catalytic bromination may be regioselective and stereochemistry-determining. A complex between the catalyst and substrate was observed by NMR spectroscopy, revealing a specific association. Finally, the products of these reactions may be subjected to regioselective metal-halogen exchange and trapping with I2, setting the stage for utility.