53178-27-1

Upstream product

• 171513-89-6 (R)-2-[(E)-1,3-diphenylprop-2-en-1-yl]-1H-isoindole-1,3-(2H)-dione 
• 85-44-9 phthalic anhydride 
• 2935-35-5 (S)-2-phenylglycine 
• 22509-74-6 N-ethoxycarbonylphthalimide 
• 20989-17-7 (2S)-2-phenylglycinol 

Downstream Products

• 69044-00-4 (S)-N-phthaloylphenylglycine methyl ester 
• 1239896-95-7 N-phthaloyl-(S)-2-phenylglycyl chloride 

Relevant academic research and scientific papers

A New Ligand Design Based on London Dispersion Empowers Chiral Bismuth-Rhodium Paddlewheel Catalysts

Heterobimetallic bismuth-rhodium paddlewheel complexes with phenylglycine ligands carrying TIPS-groups at the meta-positions of the aromatic ring exhibit outstanding levels of selectivity in reactions of donor/acceptor and donor/donor carbenes; at the same time, the reaction rates are much faster and the substrate scope is considerably wider than those of previous generations of chiral [BiRh] catalysts. As shown by a combined experimental, crystallographic, and computational study, the new catalysts draw their excellent application profile largely from the stabilization of the chiral ligand sphere by London dispersion (LD) interactions of the peripheral silyl substituents.

Efficient Kinetic Resolution of Sulfur-Stereogenic Sulfoximines by Exploiting CpXRhIII-Catalyzed C?H Functionalization

Chiral sulfoximines with stereogenic sulfur atoms are promising motifs in drug discovery. We report an efficient method to access chiral sulfoximines through a C?H functionalization based kinetic resolution. A rhodium(III) complex equipped with a chiral Cpx ligand selectively participates in conjunction with phthaloyl phenylalanine in the C?H activation of just one of the two sulfoximine enantiomers. The intermediate reacts with various diazo compounds, providing access to chiral 1,2-benzothiazines with synthetically valuable substitution patterns. Both sulfoximines and 1,2-benzothiazines were obtained in high yields and excellent enantioselectivity, with s-values of up to 200. The utility of the method is illustrated by the synthesis of the key intermediates of two pharmacologically relevant kinase inhibitors.

Chiral sensors for determining the absolute configurations of α-amino acid derivatives

A simple strategy for configurational assignments of alpha-amino acids has been developed by comparison of the proton NMR chemical shift values of the alpha hydrogens of N-phthaloyl protected alpha-amino acids in the presence of (R)-CSA 1 and (S)-CSA 1, respectively. Highly resolved NMR spectra can be obtained directly on the mixed solution of the chiral solvating agents with N-phthaloyl protected alpha-amino acids in NMR tubes, giving well distinguishable proton signals without interference which dramatically improve the accuracy of assignment and hasten the assigning procedure. The strategy is widely applicable for varied natural and non-natural amino acids.

1,2-Hydride Migration in Dialkyl α-Diazophosphonates Catalyzed by [Cu(MeCN)4]PF6: A Novel Approach to β-Amino (E)-Enylphosphonates

The regiospecific and stereoselective 1,2-migration reaction of dialkyl α-diazophosphonates for the synthesis of β-amino (E)-enylphosphonates is developed utilizing tetrakis(acetonitrile)copper(I) hexafluorophosphate [Cu(MeCN)4PF6] as the catalyst and N,N-dimethylformamide as an additive. A possible mechanism for the 1,2-migration reaction involving a metal carbene is presented. An investigation on the E/Z isomer selectivity of this process demonstrates that steric factors play an important role on the outcome. This process provides a straightforward access to β-amino (E)-enylphosphonates in moderate to good yields.

Design, synthesis and mechanism of novel shikonin derivatives as potent anticancer agents

In this study, a series of novel shikonin derivatives (30-49) were designed and synthesized and their anti-proliferative activities were evaluated against five different cancer cell lines, including HeLa, HepG2, MCF-7, BGC and A549. Some of the compounds show strong anti-proliferative effects against HeLa, HepG2 and MCF-7 with IC50 values ranging from 1.26 to 18.50 μM and show lower side effects towards normal cell lines as compared to shikonin. Compared to other compounds and shikonin itself, compound 40 displayed much stronger anti-proliferative effects against various cancer cell lines. Furthermore, the flow cytometry results demonstrated that compound 40 could obviously induce apoptosis in a dose- and time-dependent manner and also cause cell cycle arrest at the G2/M phase. For further investigation of the aforementioned mechanisms, we performed Western blot experiments and found that the cleavage of PARP and upstream caspase-3 increased; moreover, caspase-9 was activated by cleavage but not caspase-8. These aforementioned results also indicate that compound 40 could induce caspase-9 involved apoptosis and G2/M phase cell cycle arrest via the P21, p-CDC2 (Tyr15) pathway independent of P53.

Diastereoselective synthesis of γ-phthalimido-β-hydroxy esters and n-protected 4-amino-1,3-diols starting from natural α-amino acids

An efficient diastereoselective synthes.is of γ-phthalimido-β- hydroxy esters and N-protected 4-amino-1,3- diols, starting from natural amino acids is described. The key synthetic strategies involve diastereoselective reduction of γ-phthalimido-β-keto esters with NaBH4 as hydride reducing. The diastereoselective reduction has been found to be highly selective if carried out in methanol at -78°C. Furthermore, the resulting diastereomeric mixture of the reduced products was successfully and cleanly separated by column chromatography.

Cyclic amides

Cyclic amides are inhibitors of tumor necrosis factor and can be used to combat cachexia, endotoxic shock, and retrovirus replication. A typical embodiment is 3-phenyl-3-(1-oxoisoindolin-2-yl)propionamide.

Palladium-catalysed asymmetric allylic substitution: Synthesis of α- and β-amino acids

Methodology has been established for the formation of enantiomerically enriched α-amino acids using palladium-catalysed allylic amination. The formation of enantiomerically enriched allylamines has been achieved with high enantioselectivity. Oxidative cleavage of the allylamines provides arylglycine and glutamic acid derivatives. Additionally, enantiomerically enriched β-amino acids have been prepared in high enantiomeric excess. Palladium-catalysed asymmetric allylic substitution is used as the key synthetic transformation.