68839-08-7

Upstream product

• 139623-43-1 (S)-2-[(E)-1-(Diethoxy-phosphoryl)-2-phenyl-ethylimino]-7,7-dimethyl-bicyclo[2.2.1]heptane-1-carboxylic acid 
• 220586-54-9 diethyl(-)-(2S,3R)-(3-phenyl-2-H-aziridin-2-yl) phosphonate 
• 66609-42-5 D-Phenylalanine phosphonate 
• 122-51-0 orthoformic acid triethyl ester 
• 350479-90-2 (S,E)-N-benzylidene-4-methylbenzenesulfinamide 
• 220586-52-7 diethyl (S_s,2S,3R)-(-)-N-(p-toluenesulfinyl)-3-phenylaziridine-2-phosphonate 
• 220586-50-5 diethyl (S_s,1S,2R)-1-chloro-2-phenyl-2-(p-toluenesulfinamido)ethylphosphonate 
• 919-19-7 diethyl acetylphosphonate 
• 78980-61-7 diethyl [1-(acetylamino)ethen-1-yl]phosphonate 
• 221375-48-0 (N(E),R)-2-methyl-N-(2-phenylethylidene)-2-propanesulfinamide 
• 139623-40-8 (S)-2-[(E)-Diethoxy-phosphorylmethylimino]-7,7-dimethyl-bicyclo[2.2.1]heptane-1-carboxylic acid 
• 50917-70-9 (benzylaminomethyl)phosphonic acid diethyl ester 
• 141207-33-2 [(S)-1-((1S,3S)-3-Hydroxy-1-methyl-butoxy)-2-phenyl-ethyl]-phosphonic acid diethyl ester 
• 141207-36-5 (1R)-diethyl 1-hydroxy-2-phenylethylphosphonate 

Relevant academic research and scientific papers

Chirality-Driven Mode of Binding of α-Aminophosphonic Acid-Based Allosteric Inhibitors of the Human Farnesyl Pyrophosphate Synthase (hFPPS)

Thienopyrimidine-based allosteric inhibitors of the human farnesyl pyrophosphate synthase (hFPPS), characterized by a chiral α-aminophosphonic acid moiety, were synthesized as enantiomerically enriched pairs, and their binding mode was investigated by X-ray crystallography. A general consensus in the binding orientation of all (R)- and (S)-enantiomers was revealed. This finding is a prerequisite for establishing a reliable structure-activity relationship (SAR) model.

Pharmacophore Mapping of Thienopyrimidine-Based Monophosphonate (ThP-MP) Inhibitors of the Human Farnesyl Pyrophosphate Synthase

The human farnesyl pyrophosphate synthase (hFPPS), a key regulatory enzyme in the mevalonate pathway, catalyzes the biosynthesis of the C-15 isoprenoid farnesyl pyrophosphate (FPP). FPP plays a crucial role in the post-translational prenylation of small GTPases that perform a plethora of cellular functions. Although hFPPS is a well-established therapeutic target for lytic bone diseases, the currently available bisphosphonate drugs exhibit poor cellular uptake and distribution into nonskeletal tissues. Recent drug discovery efforts have focused primarily on allosteric inhibition of hFPPS and the discovery of non-bisphosphonate drugs for potentially treating nonskeletal diseases. Hit-to-lead optimization of a new series of thienopyrimidine-based monosphosphonates (ThP-MPs) led to the identification of analogs with nanomolar potency in inhibiting hFPPS. Their interactions with the allosteric pocket of the enzyme were characterized by crystallography, and the results provide further insight into the pharmacophore requirements for allosteric inhibition.

Asymmetric synthesis of aziridine 2-phosphonates from enantiopure sulfinimines (N-sulfinyl imines). Synthesis of α-amino phosphonates

An aza-Darzens reaction, involving the addition of chloromethylphosphonate anions to enantiopure sulfinimines, has been developed for the asymmetric synthesis of aziridine 2-phosphonates. Best results involve cyclization of the syn and anti diastereomeric

Asymmetric synthesis of aziridinyl phosphonates using Darzens-type reaction of chloromethyl phosphonate to chiral sulfinimines

Darzens-type reaction of chloromethyl phosphonate with (S)-(+)-N- sulfinimines gave (Ss, 2S, 3R)-diethyl 3-aryl-2-N-(p- toluenesulfinyl)aziridinylphosphonate (3) in good yields.

Enantioselective ester hydrolysis catalyzed by imprinted polymers. 2

Highly cross-linked network polymers prepared by molecular imprinting catalyzed enantioselectively the hydrolysis of N-tert-butoxycarbonyl phenylalanine-p-nitrophenyl ester (BOCPheONP). The templates were designed to allow incorporation of the key catalytic elements, found in the proteolytic enzyme chymotrypsin, into the polymer active sites. Three model systems were evaluated. These were constructed from a chiral phosphonate analogue of phenylalanine (series A, C) or L-phenylalanine (series B) attached by a labile ester linkage to an imidazole-containing vinyl monomer. Free radical copolymerization of the template with methacrylic acid (MAA) and ethylene glycol dimethacrylate (EDMA) gave a highly cross-linked network polymer. The templates could be liberated from the polymers by hydrolysis, giving catalytically active sites envisaged to contain an enantioselective binding site, a site complementary to a transition state like structure (series A, C), and a hydroxyl, imidazole, and carboxylic acid group at hydrogen bond distance. As predicted, the enantiomer of BOCPheONP complementary to the configuration of the template was preferentially hydrolyzed with D-selectivity for the series A polymers (kD/kL= 1.9) and L-selectivity for the series B polymers (kL/kD = 1.2). The maximum rate enhancement, when compared with a control polymer, prepared using a benzoyl-substituted imidazole monomer as template, was 2.5, and comparing with the imidazole monomer in solution, a maximum rate enhancement of 10 was observed. The catalytic activity was higher for polymers subjected to the nucleophilic treatment. This was explained by a higher site density and flexibility of the polymer matrix caused by this treatment. In a comparison of template rebinding to polymers imprinted with a template containing either a carboxylate (planar ground state structure) or a phosphonate (tetrahedral transition state like structure) functionality, it was observed that imprinted polymers are able to discriminate between a transition state like and a ground state structure for transesterification. However the influence of transition state stabilization on the observed rate enhancements remains obscure. Only at acidic pH's was catalysis observed, whereas at basic pH's the polymers inhibit the reaction. At a later stage, the catalytic activity of the polymers for nonactivated D- and L-phenylalanine ethyl esters was investigated. A rate enhancement of up to 3 was observed when compared to the blank. Most important, however, the polymers imprinted with a D template preferentially hydrolyzed the D-ethyl ester and exhibited saturation kinetics.

Asymmetric synthesis of aziridine 2-phosphonates and azirinyl phosphonates from enantiopure sulfinimines

Enantiopure sulfinimine (S)-4 was employed in a Darzens-type synthesis of aziridine 2-phosphonates (-)-7/(+)-8 which were transformed into α-amino phosphonates (S)-11/(R)-12 and the first enantiopure examples of azirinyl phosphonates 13-15.

Alkylation of chiral phosphonoglycine equivalents: Asymmetric synthesis of diethyl α-amino-α-alkyl-phosphonates

A model was developed to rationalize the experimental results of the alkylation of chiral phosphonoglycine equivalents yielding α-amino-α-alkyl-phosphonates. The model studies, carried out using semiempirical calculations, have emphasized the role of the chelating effects in influencing the diastereoselectivity of the alkylation step. Chelation can be optimized by tuning the functionality of the substituent at carbon C-1 of the camphor skeleton. By employing 2d, as suggested by the modelling, a major improvement in the enantiomeric excesses of compounds 5 (R = CH3, C2H5) was obtained.

Asymmetric synthesis of diethyl α-amino-α-alkyl-phosphonates by alkylation of the chiral Schiff base derived from (+)-ketopinic acid and diethylaminomethyl phosphonate

The alkylation of the chiral Schiff base derived from the condensation of (+)-ketopinic acid and diethyl aminomethylphosphonate followed by hydrolysis affords diethyl (S)-α-amino-α-alkyl phosphonates with high enantiomeric excesses when benzyl or allyl ha

Enantioselective Synthesis of α-Amino Phosphonic Acids by an Application of Stereoselective Opening of Homochiral Dioxane Acetals with Triethyl Phosphite

Stereoselective opening of homochiral acetals (2a-c) with triethyl phosphite was applied to the enantioselective synthesis of phosphono alcohols (1a-c), which were succssefully converted to the α-amino phosphonic acid diethyl esters (6a-c).

Asymmetric synthesis of diethyl α-amino-α-alkyl-phosphonates by alkylation of chiral phosphonoglycine equivalents: Role of chelating effects

Diethyl α-amino-α-alkyl-phosphonates are obtained in good to high enantiomeric excesses by alkylation of chiral phosphonoglycine equivalents embodying the camphor skeleton. The chelating effects in the alkylation step play an important role in enhancing t