1609403-89-5

Upstream product

• 604798-42-7 (3R,4R)-(1-benzyl-4-benzyloxypyrrolidin-3-yl)methanol 
• 853270-48-1 (3S,4R)-1-Benzyl-3-(benzyloxymethoxy)-4-(benzyloxymethyl)pyrrolidine 
• 797050-32-9 (2S,3R)-3-benzyloxymethyl-2-benzyloxy-methoxy-1,4-butanediol 
• 383368-52-3 diethyl (2S,3R)-3-benzoyloxymethyl-2-benzyloxymethoxysuccinate 
• 853270-47-0 (2S,3S)-2-(Benzyloxymethoxy)-3-(benzyloxymethyl)butane-1,4-diyl dimethanesulfonate 
• 849935-87-1 (3S,4S)-N-tert-butoxycarbonyl-3-hydroxy-4-hydroxymethylpyrrolidine 
• 397883-77-1 (3S,4S)-3-hydroxy-4-hydroxymethylpyrrolidine 
• 1027-35-6 1-Benzyl-4-oxo-pyrrolidine-3-carboxylic Acid Ethyl Ester 
• 795-18-6 3-(benzyl-ethoxy-carbonylmethyl-amino)-propionic acid ethyl ester 
• 3783-61-7 diethyl 2-azabutane-1,4-dicarboxylate 
• 253129-03-2 (3R, 4R)-1-benzyl-4-(hydroxymethyl)pyrrolidin-3-ol 
• 24424-99-5 di-tert-butyl dicarbonate 
• 267421-93-2 (3R,4R)-3-hydroxy-4-(hydroxymethyl)pyrrolidine 
• 849935-77-9 ethyl (3S,4R)-1-benzyl-4-hydroxypyrrolidine-3-carboxylate 

Relevant academic research and scientific papers

Syntheses and bio-activities of the l-enantiomers of two potent transition state analogue inhibitors of purine nucleoside phosphorylases

(1R)-1-(9-Deazahypoxanthin-9-yl)-1,4-dideoxy-1,4-imino-l-ribitol [(+)-5] and (3S,4S)-1-[(9-deazahypoxanthin-9-yl)methyl]-4-(hydroxymethyl)pyrrolidin-3-ol [(-)-6] are the l-enantiomers of immucillin-H (d-ImmH) and DADMe-immucillin-H (d-DADMe-ImmH), respectively, these d-isomers being high affinity transition state analogue inhibitors of purine nucleoside phosphorylases (PNPases) developed as potential pharmaceuticals against diseases involving irregular activation of T-cells. The C-nucleoside hydrochloride d-ImmH [(-)-5)·HCl], now "Fodosine" is in phase II clinical trials as an anti-T-cell leukaemia agent, while d-DADMe-ImmH is a second generation inhibitor with extreme binding to the target enzyme and has entered the clinic for phase I testing as an anti-psoriasis drug. Since the enantiomers of some pharmaceuticals have revealed surprising biological activities, the l-nucleoside analogues (+)-5·HCl and (-)-6, respectively, of d-ImmH and d-DADMe-ImmH, were prepared and their PNPase binding properties were studied. For the synthesis of compound (-)-6 suitable enzyme-based routes to the enantiomerically pure starting material (3S,4S)-4-(hydroxymethyl)pyrrolidin-3-ol [(-)-16] and its enantiomer were developed. The l-enantiomers (+)-5·HCl and (-)-6 bind to the PNPases approximately 5- to 600-times less well than do the d-compounds, but nevertheless remain powerful inhibitors with nanomolar dissociation constants. The Royal Society of Chemistry 2006.

An aza-nucleoside, fragment-like inhibitor of the DNA repair enzyme alkyladenine glycosylase (AAG)

The DNA repair enzyme AAG has been shown in mice to promote tissue necrosis in response to ischaemic reperfusion or treatment with alkylating agents. A chemical probe inhibitor is required for investigations of the biological mechanism causing this phenomenon and as a lead for drugs that are potentially protective against tissue damage from organ failure and transplantation, and alkylative chemotherapy. Herein, we describe the rationale behind the choice of arylmethylpyrrolidines as appropriate aza-nucleoside mimics for an inhibitor followed by their synthesis and the first use of a microplate-based assay for quantification of their inhibition of AAG. We finally report the discovery of an imidazol-4-ylmethylpyrrolidine as a fragment-sized, weak inhibitor of AAG.

DEAZAPURINE ANALOGS OF 1'-AZA-L-NUCLEOSIDES

The invention relates to compounds of the formula (I), which are L-enantiomeric forms of nucleoside analogues, and to pharmaceutical compositions containing the compounds, methods of treating certain diseases, including cancer, bacterial infection, parasitic infection, and T-cell mediated diseases, using the compounds, processes for preparing the compounds, and intermediates useful in the preparation of the compounds.

Process for the preparation of substituted pyrrolidine derivatives and intermediates

Two syntheses are provided; one for the preparation of (3R,4R)-4-(hydroxymethyl)pyrrolidin-3-ol, and other for the preparation of (3S,4R)-4-(hydroxymethyl)pyrrolidin-3-ol. (3R,4R)-4-(hydroxymethyl)pyrrolidin-3-ol is prepared using the achiral ylide prepared from benzylamine instead of phenethylamine (Scheme 3) which provides a crystalline intermediate. The synthesis of (3S,4R)-4-(hydroxymethyl)pyrrolidin-3-ol is achieved from (S)-diethylmalate as described in Scheme 4. A process for preparing camphor sultam is also provided.

An efficient stereoselective synthesis of (3S,4R)-4-(hydroxymethyl) pyrrolidin-3-ol from (S)-diethylmalate

A concise stereoselective synthesis of an imino sugar, (3S,4R)-4- (hydroxymethyl)pyrrolidin-3-ol from (S)-diethylmalate has been developed in five steps and in overall yield of 28%.

METHOD FOR PREPARING 3-HYDROXY-4-HYDROXYMETHYL-PYRROLIDINE COMPOUNDS

This invention relates to a method of preparing (3R,4R)-3-hydroxy-4-hydroxymethylpyrrolidine, a key intermediate compound for the synthesis of certain inhibitor compounds, including the step of enzyme catalysed enantioselective esterification of an hydroxy group of an hydroxypyrrolidine. The invention further relates to a method for preparing (3S,4S)-3-hydroxy-4-hydroxymethylpyrrolidine, which is the enantiomer of (3R,4R)-3-hydroxy-4-hydroxymethylpyrrolidine.

A practical large-scale synthesis of (3R,4R)-4-(Hydroxymethyl)pyrrolidin-3- ol via asymmetric 1,3-dipolar cycloaddition

(3R,4R)-4-(Hydroxymethyl)pyrrolidin-3-ol (1), which is a useful intermediate for the synthesis of various bioactive molecules, has been synthesized in 51% overall yield by 1,3-dipolar cycloaddition reaction from the dipolarophile, (E)-3-benzyloxypropenoyl-(2′S)-bornane-10,2-sultam (5), and the achiral ylide precursor, N-(benzyl)-N-(methoxymethyl)-N- (trimethylsilylmethyl)amine (6), without using chromatography and the subsequent reduction with LAH and catalytic hydrogenation. The diastereomers 7 and 8 were separated by crystallization, and efficient procedures were developed for the subsequent reactions to afford 1.

INHIBITORS OF NUCLEOSIDE PHOSPHORYLASES AND NUCLEOSIDASES

The present invention relates to compounds of the general formula (I) which are inhibitors of purine muclioside phosphorylases (PNP), purine phosphoribosyltransferases (PPRT), 5'-methylthioadenosine phosphorylases (MTAP), 5'-methylthioadenosine mucliosidases (MTAN) and/or nucleoside hydrolases (NH). The invention also relates to the use of these compounds in the treatment of diseases and infections including cancer, bacterial infections, protozoal infections, and T-cell mediated disease and to pharmaceutical compositions containing the compounds

Synthesis of Second-Generation Transition State Analogues of Human Purine Nucleoside Phosphorylase

Purine nucleoside phosphorylases (PNPs) catalyze nucleophilic displacement reactions by migration of the cationic ribooxacarbenium carbon between the fixed purine and phosphate nucleophiles. As the phosphorolysis reaction progresses along the reaction coo

Synthesis of enantiomerically pure 4-substituted pyrrolidin-3-ols via asymmetric 1,3-dipolar cycloaddition

Asymmetric 1,3-dipolar cycloadditions of chiral azomethine ylides to 3-benzyloxy-substituted alkenoylcamphorsultams are described. trans-3,4-Disubstituted pyrrolidines containing a protected hydroxyl group at C(4) of the pyrrolidine ring are obtained in high diastereomeric ratios. Such compounds can serve as chiral building blocks for the syntheses of enantiopure bioactive pyrrolidines. This is exemplified by a short synthetic route to a known glycosidase inhibitor, (3R,4R)-4-(hydroxymethyl)pyrrolidin-3-ol and its enantiomer.