340166-80-5

Upstream product

• 100-46-9 benzylamine 
• 62965-35-9 N-tert-butyloxycarbonyl-L-tert-leucine 
• 24424-99-5 di-tert-butyl dicarbonate 
• 20859-02-3 L-tert-Leucine 

Downstream Products

• 340166-83-8 (S)-2-[3-((1R,2R)-2-Amino-cyclohexyl)-ureido]-N-benzyl-3,3-dimethyl-butyramide 
• 207121-91-3 (S)-N-benzyl 2-amino-3,3-dimethylbutanamide 

Relevant academic research and scientific papers

New thiourea organocatalysts and their application for the synthesis of 5-(1H-indol-3-yl)methyl-2,2-dimethyl-1,3-dioxane-4,6-diones a source of chiral 3-indoylmethyl ketenes

The stereoselective properties of modified thiourea organocatalysts were tested in the Friedel–Crafts alkylation of indole with 5-arylidene-2,2-dimethyl-1,3-dioxane-4,6-diones, which produces chiral 5-((1H-indol-3-yl)(aryl)methyl)-2,2-dimethyl-1,3-dioxane-4,6-diones. Based on a tentative reaction mechanism for ((S)-N-benzyl-2-(3-(3,5-bis(trifluoromethyl)phenyl)thioureido)-N,3,3-trimethylbutanamide organocatalysts, modifications were applied in four selected regions. Systematic structure-stereoselectivity relationship study allowed designing the best efficient organocatalyst for the investigated Friedel–Crafts alkylation of indole with 5-arylidene-2,2-dimethyl-1,3-dioxane-4,6-diones.

Study on anti-proliferative activity in cancer cells and preliminary structure–activity relationship of pseudo-peptide chiral thioureas

In our previous studies, we have shown that thiourea compounds containing phosphate esters have potent antitumor activity and can be used as a novel strategy for the development of antitumor agents. Herein, a series of novel phosphonate thioureas 5–38 have been synthesized, which were fully characterized by 1H NMR,13C NMR spectrum, elemental analysis. Three human cancer cell lines (Bcap-37, BGC-823, and PC-3) have been used to investigate these compounds’ antitumor activities. After the summarization of the structure–activity relationships, we found that the variation of R, R1, and R2 in these novel phosphonate thioureas contribute to the antitumor activities. All these SAR-guided efforts may lead to novel antitumor drugs in the market in the near future.

l-tert-Leucine-Derived AmidPhos-Silver(I) Chiral Complexes for the Asymmetric [3+2] Cycloaddition of Azomethine Ylides

The l-tert-leucine-derived AmidPhos/silver(I) catalytic system has been developed for the asymmetric [3+2] cycloaddition of azomethine ylides with electronic-deficient alkenes with or without Et3N. Under optimal conditions, highly functionalized endo-4-pyrrolidines were obtained with modest to high yields (up to 99% yield) and enantioselectivities (up to 98% ee).

Bifunctional Iminophosphorane Catalyzed Enantioselective Sulfa-Michael Addition to Unactivated α-Substituted Acrylate Esters

The highly enantioselective sulfa-Michael addition of alkyl thiols to unactivated α-substituted acrylate esters catalyzed by a bifunctional iminophosphorane organocatalyst under mild conditions is described. The strong Br?nsted basicity of the iminophosphorane moiety of the catalyst provides the necessary activation of the alkyl thiol pro-nucleophile, while the two tert-leucine residues flanking a central thiourea hydrogen-bond donor facilitate high enantiofacial selectivity in the protonation of the transient enolate intermediate. The reaction is broad in scope with respect to the alkyl thiol, the ester moiety, and the α-substituent of the α,β-unsaturated ester, affords sulfa-Michael adducts in excellent yields (up to >99%) and enantioselectivities (up to 96% ee), and is amenable to decagram scale-up using catalyst loadings as low as 0.05 mol %.

Primary amino acid derivatives: Compounds with anticonvulsant and neuropathic pain protection activities

Pharmacological management remains the primary method to treat epilepsy and neuropathic pain. We have advanced a novel class of anticonvulsants termed functionalized amino acids (FAAs). In this study, we examine FAA derivatives from which the terminal acetyl moiety was removed and termed these compounds primary amino acid derivatives (PAADs). Twenty-seven PAADs were prepared; the central C(2) R-substituent was varied, including C(2) stereochemistry, and the compounds were tested in rodent models of seizures and neuropathic pain. C(2)-Hydrocarbon N-benzylamide PAADs were potent anticonvulsants and excellent anticonvulsant activity (mice, ip; rat, po) was observed for C(2) R-substituted PAADs in which the R group was ethyl, isopropyl, or tert-butyl, and the C(2) stereochemistry conformed to the d-amino acid configuration ((R)-stereoisomer). These values surpassed the activities of several clinical antiepileptic drugs. The C(2) (R)-ethyl and C(2) (R)-isopropyl PAADs also displayed excellent activities in the mouse (ip) formalin neuropathic pain model. Significantly, unlike the FAA structure-activity relationship, PAAD anticonvulsant activity increased upon substitution of a methylene unit for a heteroatom in the R-substituent that was one atom removed from the C(2) site, suggesting that these PAADs function by a different pathway than FAAs.

Stereoselective nucleophilic addition to imines catalyzed by chiral bifunctional thiourea organocatalysts

A new and easy synthesis of chiral bifunctional organic catalysts obtained by the combination of (S)-t-leucine-derivatives with (1R,2R)-trans-1,2-diamino-cyclohexane was developed. A few compounds, representatives of a class of organocatalysts containing a thiourea group and a tertiary amino group connected through a chiral backbone, have been successfully synthesized. The catalytic behaviour of such bifunctional chiral molecules, either neutral or protonated species, was investigated in the addition of acetylacetone to β-nitrostyrene as a model reaction. Using the best conditions, high yields and enantioselectivities of up to 85% were obtained. The same metal free catalysts were then employed in the addition of activated nucleophiles to imines: in the reaction of 1,3-diketones with N-CBz imines, the products were isolated in up to 61% ee, while in the reaction with diethyl malonate enantioselectivities up to 71% were reached.