87691-27-8

Usage

Chemical Properties

White powder

InChI:InChI=1/C10H17NO5/c1-10(2,3)16-9(15)11-5-6(12)4-7(11)8(13)14/h6-7,12H,4-5H2,1-3H3,(H,13,14)/t6-,7-/m0/s1

Upstream product

• 84348-37-8 N-tert-butoxycarbonyl-4-oxo-L-proline 
• 24424-99-5 di-tert-butyl dicarbonate 
• 618-27-9 hydroxy L-proline 
• 440678-63-7 (2S,4R)-1-tert-butyl 2-ethyl 4-hydroxypyrrolidine-1,2-dicarboxylate 
• 13726-69-7 (2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid 
• 502442-53-7 ethyl (4S)-2-(N-tert-butyloxycarbonylamino)-4,5-dihydroxy-2-pentenoate 
• 502442-56-0 ethyl (4S)-2-(N-tert-butyloxycarbonylamino)-5-tert-butyldimethylsiloxy-2-pentenoate 
• 502442-62-8 ethyl (4S)-N-tert-butyloxycarbonyl-4-tert-butyldiphenylsiloxy-α,β-didehydroprolinate 
• 502442-64-0 ethyl (2S,4S)-N-tert-butyloxycarbonyl-4-tert-butyldiphenylsiloxyprolinate 
• 502442-60-6 ethyl (4S)-2-(N-tert-butyloxycarbonylamino)-4-tert-butyldiphenylsiloxy-5-hydroxy-2-pentenoate 
• 502442-58-2 ethyl (4S)-2-(N-tert-butyloxycarbonylamino)-5-tert-butyldimethylsiloxy-4-tert-butyldiphenylsiloxy-2-pentenoate 
• 74844-91-0 (2S,4S)-N-tert-butoxycarbonyl-4-hydroxyproline methyl ester 
• 87250-97-3 2’-methyl-2’-propanyl (1S,4S)-3-oxo-2-oxa-5-azabicyclo[2.2.1]heptane-5-carboxylate 
• 87250-97-3 tert-butyl 3-oxo-2-oxa-5-azabicyclo[2.2.1]heptane-5-carboxylate 

Downstream Products

• 84348-37-8 N-tert-butoxycarbonyl-4-oxo-L-proline 
• 132073-36-0 (2S,4S)-2-[(S)-1-(Benzyl-methyl-carbamoyl)-2-phenyl-ethylcarbamoyl]-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester 
• 146060-16-4 (2S,4S)-1-(tert-butoxycarbonyl)-4-ethoxypyrrolidine-2-carboxylic acid 
• 177607-77-1 (2S,4S)-2-((S)-1-Benzyloxycarbonyl-ethylcarbamoyl)-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester 
• 618-27-9 hydroxy L-proline 
• 266337-25-1 (4S)-1-(tert-butoxycarbonyl)-4-hydroxy-L-prolinamide 
• 74844-91-0 (2S,4S)-N-tert-butoxycarbonyl-4-hydroxyproline methyl ester 
• 132622-90-3 (2S,4S)-2-benzyl 1-tert-butyl 4-hydroxypyrrolidine-1,2-dicarboxylate 
• 401564-17-8 (2S,4S)-1-(tert-butoxycarbonyl)-4-((tert-butyldimethylsilyl)oxy)pyrrolidine-2-carboxylic acid 
• 960390-07-2 1,1-dimethylethyl (2S,4S)-2-[({(1R,2S)-2-ethenyl-1-[(ethyloxy)carbonyl]cyclopropyl}amino)carbonyl]-4-hydroxy-1-pyrrolidinecarboxylate 
• 401564-34-9 3-((2S,4S)-1-tert-butoxycarbonyl-4-hydroxy-2-pyrrolidinylcarbonyl)-1,3-thiazolidine 
• 401565-07-9 3-((2S,4S)-4-benzoyloxy-1-tert-butoxycarbonyl-2-pyrrolidinylcarbonyl)-1,3-thiazolidine 
• 401565-08-0 3-[(2S,4S)-4-(4-cyanobenzoyloxy)-1-tert-butoxycarbonyl-2-pyrrolidinylcarbonyl]-1,3-thiazolidine 
• 870992-70-4 N-tert-butoxycarbonyl-(2S,4R)-4-fluoroprolylglycine benzyl ester 

Relevant academic research and scientific papers

Automated Radiosynthesis of cis- And trans-4-[18F]Fluoro- l -proline Using [18F]Fluoride

The positron emission tomography imaging agents cis- and trans-4-[18F]fluoro-l-proline are used for the detection of numerous diseases such as pulmonary fibrosis and various carcinomas. These imaging agents are typically prepared by nucleophilic fluorination of 4-hydroxy-l-proline derivatives, with [18F]fluoride, followed by deprotection. Although effective radiofluorination reactions have been developed, the overall radiosynthesis process is suboptimal due to deprotection methods that are performed manually, require multiple steps, or involve harsh conditions. Here we describe the development of two synthetic routes that allow access to precursors, which undergo highly selective radiofluorination reactions and rapid deprotection, under mild acidic conditions. These methods were found to be compatible with automation, avoiding manual handling of radioactive intermediates.

Orthogonal Catalysis for an Enantioselective Domino Inverse-Electron Demand Diels?Alder/Substitution Reaction

An enantioselective domino process for the synthesis of substituted 1,2-dihydronaphthalenes has been developed by the combination of chiral amines and a bidentate Lewis acid in an orthogonal catalysis. This new method is based on an inverse electron-demand Diels?Alder and a subsequent group exchange reaction. An enamine is generated in situ from an aldehyde and a chiral secondary amine catalyst that reacts with phthalazine, activated by the coordination to a bidentate Lewis acid catalyst. The absolute configuration of the product is controlled by chiral information provided by the amine. The formed ortho-quinodimethane intermediate is then transformed via a group exchange reaction with thiols. The new method shows a broad scope and tolerates a wide range of functional groups with enantiomeric ratios up to 91 : 9. All-in-all, this enantioselective synthesis tool provides an easy access to complex 1,2-dihydronaphthalenes starting from readily available phthalazine, aldehydes and thiols in a combinatorial way.

Synthesis process of N-BOC-cis-4-hydroxyproline methyl ester

The invention discloses a synthesis process of N-BOC-cis-4-hydroxyproline methyl ester. The synthesis process comprises the following steps: (1) adding raw materials including dichloromethane, 4-hydroxy-L-proline and DMAP into a 2 L reaction flask, stirring, slowly dropwise adding BOC anhydride into the reaction liquid, after dropwise adding, sampling, carrying out TLC, completely reacting the rawmaterials, adding water into the reaction liquid after treatment, stirring at a temperature of 20-30 DEG C, separating the liquid, drying an organic phase by using anhydrous sodium sulfate, and concentrating under reduced pressure to obtain a white solid product; and (2) taking the obtained product, adding tetrahydrofuran and DCC into a 5 L reaction flask, stirring at 20-30 DEG C to react for 1 hour, dropwise adding methanol into the reaction solution, keeping the temperature after dropwise adding, sampling, carrying out TLC until the reaction is complete, filtering the reaction solution, collecting the filtrate, concentrating under reduced pressure until no liquid flows out to obtain a white solid crude product, heating, collecting the filtrate, collecting a filter cake, and drying the filter cake to obtain a white solid. According to the invention, the product is prepared with high quality and high yield.

Modular Chemoenzymatic Synthesis of GE81112 B1 and Related Analogues Enables Elucidation of Its Key Pharmacophores

The GE81112 complex has garnered much interest due to its broad antimicrobial properties and unique ability to inhibit bacterial translation initiation. Herein we report the use of a chemoenzymatic strategy to complete the first total synthesis of GE81112 B1. By pairing iron and α-ketoglutarate dependent hydroxylases found in GE81112 biosynthesis with traditional synthetic methodology, we were able to access the natural product in 11 steps (longest linear sequence). Following this strategy, 10 GE81112 B1 analogues were synthesized, allowing for identification of its key pharmacophores. A key feature of our medicinal chemistry effort is the incorporation of additional biocatalytic hydroxylations in modular analogue synthesis to rapidly enable exploration of relevant chemical space.

Solid-phase synthesis of a novel phalloidin analog with on-bead and off-bead actin-binding activity

Specific effectors of actin polymerization have found use as dynamic probes of cellular morphology that may be used to gauge cellular response to stimuli and drugs. Of various natural products that target actin, phalloidin is one of the most potent and selective inhibitors of actin depolymerization. Phalloidin and related members of the phallotoxin family are macrocyclic heptapeptides bearing a characteristic and rigidifying transannular tryptathionine bridge. Here we describe a solid-phase synthesis of a new phalloidin analog as a prototype for library development with the potential for on- and off-bead screening. To validate our method, we labelled the phalloidin derivative with a fluorescent dye which stained actin in CHO cells. Furthermore, a bioassay was developed allowing actin polymerization on beads carrying a phalloidin derivative.

Pyrrolidine ring puckering and prolyl amide bond configurations of 2-methyl-allo-hydroxyproline-based dipeptides

An expeditious method for the synthesis of homo and heterochiral dipeptides containing l-alanine and d/l 2-methyl allo-hydroxyl prolines was developed using direct aminolysis of bicyclic lactones derived from d/l alanine. The impact of C-2 methylation and its spatial orientation on the pyrrolidine ring puckering and prolyl amide bond configuration was ascertained by solution NMR studies. The present studies reveal that C-2 methylation causes the prolyl amide bond to exist exclusively in the trans geometry in both homo- and heterochiral dipeptides. However, the spatial orientation of the C-2 methyl group and its i + 2 position in appropriately capped model dipeptides may nucleate into a turn like structure.

Method for preparing hydrobromic acid teneligliptin

The invention provides a method for preparing hydrobromic acid teneligliptin. The method includes steps of preparing L-hydroxyproline; mixing the L-hydroxyproline and sodium bicarbonate with each other to obtain mixtures, dissolving the mixtures in water, adding acetone into the water, dropping di-tert-butyl dicarbonate into the water, carrying out room-temperature reaction overnight and then treating reaction products to obtain t-butyloxycarboryl-N-hydroxyproline; preparing t-butyloxycarboryl-N-4-oxo-proline from the t-butyloxycarboryl-N-hydroxyproline; preparing (2S)-4-oxo-2-(3-thiazolidine carbonyl)-1-pyrrolidine carboxylic acid tert-butyl ester from the t-butyloxycarboryl-N-4-oxo-proline; preparing compounds III from compounds IV; preparing compounds II from the compounds III; preparing compounds 1-(3-methyl-1-phenyl-1H-pyrazole-5-base) piperazine from the compounds II; preparing intermediates I; preparing the hydrobromic acid teneligliptin from the intermediates I. The method has the advantages that the method is low in cost, and the cost of the method is only two-thirds of the cost of an existing method in the prior art; the yield of the hydrobromic acid teneligliptin is higher than 95%, and the purity of the hydrobromic acid teneligliptin is higher than 98%.

Preparation method for medical intermediate N-Boc-cis-4-hydroxy-L-proline

The invention provides a preparation method for a medical intermediate N-Boc-cis-4-hydroxy-L-proline. The preparation method comprises the following steps: with L-hydroxyproline as a raw material, subjecting the raw material to Boc protection; then carrying out hydroxyl radical oxidation so as to obtain N-Boc-4-oxo-L-proline; dissolving N-Boc-4-oxo-L-proline in a solvent and successively carrying out reduction with a reducing agent and purification at a certain temperature so as to obtain the product N-Boc-cis-4-hydroxy-L-proline. The method has the advantages of good reaction selectivity, high product ee value and low preparation cost.

SUBSTITUTED HETEROCYCLIC SULFONAMIDE COMPOUNDS USEFUL AS TRPA1 MODULATORS

The invention is concerned with the compounds of formula I or II: and salts thereof. In addition, the present invention relates to methods of manufacturing and methods of using the compounds of formula I or II as well as pharmaceutical compositions containing such compounds. The compounds may be useful in treating diseases and conditions mediated by TRPA1, such as pain.

ANTI-VIRAL COMPOUNDS

Compounds effective in inhibiting replication of Hepatitis C virus (“HCV”) are described. This invention also relates to processes of making such compounds, compositions comprising such compounds, and methods of using such compounds to treat HCV infection.