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Usage

Uses

Used in Pharmaceutical Industry:
(3S,4R)-1-benzyl-4-hydroxy-5-oxopyrrolidine-3-carboxylic acid is used as a potential therapeutic agent for various medical conditions due to its unique structural features and potential biological activities. Its chiral nature and functional groups may allow for specific interactions with biological targets, making it a candidate for the development of new drugs.
Used in Medicinal Chemistry:
(3S,4R)-1-benzyl-4-hydroxy-5-oxopyrrolidine-3-carboxylic acid is used as a building block for the synthesis of other compounds with potential pharmaceutical applications. Its structural features can be further modified or combined with other molecules to create new compounds with improved or novel therapeutic effects.
Used in Research and Development:
(3S,4R)-1-benzyl-4-hydroxy-5-oxopyrrolidine-3-carboxylic acid is used as a subject of research to explore its potential properties and applications. Scientists and researchers may study its interactions with biological systems, its effects on specific diseases or conditions, and its potential as a precursor for the synthesis of other bioactive compounds.

Upstream product

• 71336-69-1 (+/-)-trans-ethyl 1-benzyl-4-hydroxy-5-oxopyrrolidine-3-carboxylate 
• 622-30-0 N-benzyl hydroxylalmine 
• 103-49-1 dibenzylamine 
• 29601-98-7 N-benzylhydroxylamine hydrochloride 
• 3376-26-9 N-Benzylidenebenzylamine N-oxide 

Downstream Products

• 253129-03-2 (3R, 4R)-1-benzyl-4-(hydroxymethyl)pyrrolidin-3-ol 
• 502485-10-1 C₄₁H₃₉NO₆ 
• 267421-93-2 (3R,4R)-3-hydroxy-4-(hydroxymethyl)pyrrolidine 
• 362600-15-5 N-Fmoc-(3R,4R)-4-(hydroxymethyl)pyrrolidin-3-ol 
• 635319-09-4 tert-butyl (3R,4R)-3-hydroxy-4-(hydroxymethyl)pyrrolidine-1-carboxylate 
• 666831-24-9 tert-butyl (3R,4R)-3-hydroxy-4-[(methanesulfonyloxy)methyl]pyrrolidine-1-carboxylate 
• 666831-26-1 (3R,4S)-tert-butyl 3-hydroxy-4-((methylthio)methyl)pyrrolidine-1-carboxylate 
• 653592-04-2 (3R,4S)-1-((4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl)-4-((methylthio)methyl)pyrrolidin-3-ol 

Relevant academic research and scientific papers

COMPOSITIONS AND METHODS FOR THERAPY OF PROSTATE CANCER USING DRUG COMBINATIONS TO TARGET POLYAMINE BIOSYNTHESIS AND RELATED PATHWAYS

Provided are compositions and methods for treating prostate conditions. The methods involve administering to an individual in need thereof a composition that contains i) an inhibitor of methionine salvage pathway in prostate of the individual and ii) a polyamine analogue. The methods are for use in individuals who have been diagnosed with, or are suspected of having or at risk for developing androgen sensitive prostate cancer (AS-CaP), or Castration recurrent CaP (CR-CaP), or benign prostate hyperplasia (BPH). The disclosure includes use of inhibitors of methylthioadenosine phosphorylase (MTAP), and a polyamine analog that upregulates polyamine catabolism by increasing spermidine/spermine Nl -acetyl transferase (SAT1) activity, such as methylthio-DADMe-Immucillin (MTDIA), andl),N(11)-bisethylnorspermine (BENSpm), respectively. Pharmaceutical formulations that contain a combination of the inhibitor of the methionine salvage pathway and a polyamine analogue are included, as are kits that contain such agents.

Tight binding enantiomers of pre-clinical drug candidates

MTDIA is a picomolar transition state analogue inhibitor of human methylthioadenosine phosphorylase and a femtomolar inhibitor of Escherichia coli methylthioadenosine nucleosidase. MTDIA has proven to be a non-toxic, orally available pre-clinical drug candidate with remarkable anti-tumour activity against a variety of human cancers in mouse xenografts. The structurally similar compound MTDIH is a potent inhibitor of human and malarial purine nucleoside phosphorylase (PNP) as well as the newly discovered enzyme, methylthioinosine phosphorylase, isolated from Pseudomonas aeruginosa. Since the enantiomers of some pharmaceuticals have revealed surprising biological activities, the enantiomers of MTDIH and MTDIA, compounds 1 and 2, respectively, were prepared and their enzyme binding properties studied. Despite binding less tightly to their target enzymes than their enantiomers compounds 1 and 2 are nanomolar inhibitors.

Profiling base excision repair glycosylases with synthesized transition state analogs

Two base excision repair glycosylase (BER) transition state (TS) mimics, (3R,4R)-1-benzyl (hydroxymethyl) pyrrolidin-3-ol (1NBn) and (3R,4R)- (hydroxymethyl) pyrrolidin-3-ol (1N), were synthesized using an improved method. Several BER glycosylases that repair oxidized DNA bases, bacterial formamidopyrimdine glycosylase (Fpg), human OG glycosylase (hOGG1) and human Nei-like glycosylase 1 (hNEIL1) exhibit exceptionally high affinity (K d～pM) with DNA duplexes containing the 1NBn and 1N nucleotide. Notably, comparison of the Kd values of both TS mimics relative to an abasic analog (THF) in duplex contexts paired opposite C or A suggest that these DNA repair enzymes use distinctly different mechanisms for damaged base recognition and catalysis despite having overlapping substrate specificities.

Development of a practical synthesis of a purine nucleoside phosphorylase inhibitor: BCX-4208

A practical synthesis of the purine nucleoside phosphorylase (PNP) inhibitor BCX-4208 (1) was accomplished in three telescoped steps. Mannich condensation of the 4-benzyloxy-9-deazahypoxanthine with (3R,4R)-3-hydroxy-4- (hydroxymethyl)pyrrolidine and formaldehyde followed by removal of the protecting group and crystallization furnished the desired product as a hydrochloride salt in 85% overall yield and 99.8% purity. A scalable synthesis of 9-deazahypoxanthine is also reported. 2009 American Chemical Society.

A practical synthesis of (3R,4R)-N-tert-butoxycarbonyl-4- hydroxymethylpyrrolidin-3-ol

The title compound (+)-5, required for production of transition state analogue inhibitors of enzymes involved in T-cell-dependent disorders, was synthesized in five steps. A 1,3-dipolar cycloaddition of the nitrone formed from formaldehyde and N-benzylhydroxylamine to diethyl maleate gave the racemic cis-isoxazolidine (±)-7. Reduction of the N-O bond of this compound gave pyrrolidone (±)-8 in excellent yield. A very efficient enzymic resolution of this racemic product led to the title enantiomer (+)-5. This route employs only one chromatographic purification. The Royal Society of Chemistry.

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

A process for preparing (3R,4R)-3-hydroxy-4-hydroxymethylpyrrolidine, the compound of formula (I), or (3S,4S)-3-hydroxy-4-hydroxymethylpyrrolidine, the compound of formula (Ia) involving, as a key step, the enzyme-catalysed enantioselective hydrolysis of a racemic 3,4-trans-disubstituted pyrrolidinone compound of formula (II).