90365-74-5

Usage

Uses

Used in Organic Synthesis:
(3S,4S)-1-Benzylpyrrolidine-3,4-diol is used as a building block for the preparation of novel chiral crown ethers. Its unique stereochemistry and functional groups make it a versatile component in the design and synthesis of complex organic molecules with potential applications in various fields.
Used in Pharmaceutical Industry:
(3S,4S)-1-Benzylpyrrolidine-3,4-diol is used as an intermediate in the synthesis of (3R,4R)1-benzyl-4-fluoropyrrolidin-3-amine. (3S,4S)-1-Benzylpyrrolidine-3,4-diol has potential applications in the development of new pharmaceuticals, particularly in the area of drug discovery and medicinal chemistry.
Used in Nucleic Acid Chemistry:
(3S,4S)-1-Benzylpyrrolidine-3,4-diol is used as an intermediate in the preparation of 3-hydroxy-4-pyrrolidinyl analogs of nucleobases. These analogs can be incorporated into nucleic acid structures, potentially leading to the development of new nucleic acid-based therapeutics and diagnostic tools.

InChI:InChI=1/C11H15NO2/c13-10-7-12(8-11(10)14)6-9-4-2-1-3-5-9/h1-5,10-11,13-14H,6-8H2/p+1/t10-,11-/m0/s1

Upstream product

• 100-46-9 benzylamine 
• 1464-53-5 rac-1,2,3,4-diepoxybutane 
• 75172-31-5 (3R,4R)-1-benzyl-3,4-dihydroxypyrrolidine-2,5-dione 
• 87-69-4 L-Tartaric acid 
• 1031246-25-9 6-benzyl-2,3-dimethoxy-2,3-dimethylhexahydro-[1,4]dioxino[2,3-c]pyrrole 
• 136137-85-4 (3R,4R)-1-benzyl-2,5-dioxopyrrolidine-3,4-diyl diacetate 
• 187032-53-7 (3S,4S)-1-N-benzyl-3,4-dihydroxypyrrolidine-2,6-dione 
• 57495-46-2 (2S,3S)-butane-1,4-diol bis[4-methylbenzenesulfonate] 

Downstream Products

• 137945-72-3 (3S,4S)-1-Benzyl-3,4-bis(methoxymethoxy)pyrrolidine 
• 138228-44-1 (3S,4S)-3,4-dibenzoyloxy-1-benzylpyrrolidine 
• 90481-32-6 (3S,4S)-pyrrolidine-3,4-diol 
• 138228-45-2 (3S,4S)-1-benzyl-3,4-bis{[(tert-butyl)dimethylsilyl]oxy}pyrrolidine 
• 104351-40-8 (3S,4S)-1-benzyl-3,4-pyrrolidinediyl bis(methanesulfonate) 
• 144866-75-1 (3S,4S)-3,4-Bis-allyloxy-1-benzyl-pyrrolidine 
• 169619-34-5 (3S,4S)-3,4-Bis<(tert-butyldiphenylsilyl)oxy>-N-benzylpyrrolidine 
• 140134-20-9 (3R,4R)-3,4-diazido-1-benzylpyrrolidine 
• 201601-55-0 Succinic acid mono-[(3S,4S)-1-benzyl-4-(3-carboxy-propionyloxy)-pyrrolidin-3-yl] ester 
• 201601-50-5 (3S,4S)-1-benzyl-3-(tert-butyldimethylsilyl)oxy-4-hydroxypyrrolidine 
• 204002-64-2 (3S,4S)-1-Benzyl-4-(2-methoxy-ethoxymethoxy)-pyrrolidin-3-ol 
• 219317-52-9 (3S,4S)-1-benzylpyrrolidine-3,4-diyl bis(trifluoromethanesulfonate) 
• 636580-16-0 (3R,4R)-1-benzyl-3,4-bis(2-naphthylsulfanyl)pyrrolidine 
• 219505-62-1 (+)-(3R,4R)-1-benzyl-3,4-bis(phenylsulfanyl)pyrrolidine 

Relevant academic research and scientific papers

Selective Isomerization via Transient Thermodynamic Control: Dynamic Epimerization of trans to cis Diols

Traditional approaches to stereoselective synthesis require high levels of enantio- and diastereocontrol in every step that forms a new stereocenter. Here, we report an alternative approach, in which the stereochemistry of organic substrates is selectivel

Electrostatics Favor PNA : DNA Stability over Stereochemistry in Pyrrolidine-Based Cationic Dual-Backbone PNA Analogues

Modifications to the peptide nucleic acid (PNA) backbone has been well known to alter the thermodynamical parameters of PNA : DNA complexes to broaden their utility for different applications. Electrostatic interactions between a modified PNA having a positively charged backbone and the negatively charged DNA has been shown to enhance thermal stabilities of PNA : DNA complexes at various instances. On the other hand, chiral introduction in PNA backbone leads to stereochemical preference that affects binding properties. However, the interplay between electrostatics and stereochemistry has not been systematically studied so far. Herein, we report the synthesis and biophysical characterization of cationic PNA named dapPNA, first of its kind, having a dual PNA backbone constituting of a pyrrolidine ring having a β-substitution. One of the aims of this study was to investigate the role of electrostatics over stereochemical preferences. The results show that electrostatic attraction between cationic dapPNA and negatively charged DNA overcomes the unfavorable stereochemical effects and enhances stability of PNA : DNA complexes. Moreover, two different PNA backbones derived from a single PNA monomer expands the repertoire of pyrrolidine based PNA analogues.

(3S,4S)-N-substituted-3,4-dihydroxypyrrolidines as ligands for the enantioselective Henry reaction

The enantioselective Henry reaction is a very important and useful carbon–carbon bond forming reaction. The execution of this reaction requires the use of efficient chiral catalysts. In this work, in situ formed complexes of N-substituted dihydroxypyrrolidines, chiral ligands derived from L-tartaric acid and amines, were evaluated as catalysts in the enantioselective Henry reaction. The results showed that the nature of the N-substituent on the ligand significantly influences the outcome of the reaction. Best results were obtained using a Cu (II) complex of (3S,4S)-N-benzyl-3,4-dihydroxypyrrolidine, in the presence of DIPEA, for the reaction of aromatic aldehydes with nitromethane, at room temperature, originating products with er up to 92:8 (R:S) and conversions up to 96%. The interaction between the pyrrolidine ligand and the copper ion, in isopropanol, was followed by UV-vis spectrophotometry, showing a 1:1 stoichiometry and a binding constant of 4.4. The results obtained will contribute to the design and development of more efficient chiral catalysts for this type of reaction.

Synthesis of Three-Dimensional (Di)Azatricyclododecene Scaffold and Its Application to Peptidomimetics

A novel sp3 carbon-rich tricyclic 3D scaffold-based peptide mimetic compound library was constructed to target protein-protein interactions. Tricyclic framework 7 was synthesized from 9-azabicyclo[3,3,1]nonan-3-one (11) via a gold(I)-catalyzed Conia-ene reaction. The electron-donating group on the pendant alkyne of cyclization precursor 12 b–e was the key to forming 6-endo-dig cyclized product 7 with complete regioselectivity. Using the synthetic strategy for regioselective construction of bridged tricyclic framework 7, a diazatricyclododecene 3D-scaffold 8 a, which enables the introduction of substituents into the scaffold to mimic amino acid side chains, was designed and synthesized. The peptide mimetics 21 a–u were synthesized via step-by-step installation of three substituents on diazatricyclododecene scaffold 8 a. Compounds 21 a–h were synthesized as α-helix peptide mimics of hydrophobic ZZxxZ and ZxxZZ sequences (Z=Leu or Phe) and subjected to cell-based assays: antiproliferative activity, HIF-1 transcriptional activity which is considered to affect cancer malignancy, and antiviral activity against rabies virus. Compound 21 a showed the strongest inhibitory activity of HIF-1 transcriptional activity (IC50=4.1±0.8 μM), whereas compounds 21 a–g showed antiviral activity with IC50 values of 4.2–12.4 μM, suggesting that the 3D-scaffold 8 a has potential as a versatile peptide mimic skeleton.

Preorganized helical chirality controlled homochiral self-assembly and circularly polarized luminescence of a quadruple-stranded Eu2 L 4 helicate

β-Diketones are one of the most widely used ligands for sensitizing the luminescence of lanthanide complexes due to their excellent sensitization abilities. However, the difficulties in introducing chiral groups to take part in the electronic transitions of conjugated systems limit their application in lanthanide circularly polarized luminescence (CPL) materials. In view of the inherent chirality of the helical structure, herein, a pair of homochiral quadruple-stranded helicates, Eu2L4, is assembled based on chiral bis-β-diketonate ligands, wherein the two point chirality centers in the spacer preorganize the helical conformation of the ligand (3S,4S)/(3R,4R)-3,4-bis(4,4′-bis(4,4,4-trifluoro-1,3-dioxobutyl)phenoxyl)-1-benzylpyrrolidine, LSS/LRR. X-ray crystallographic analyses reveal that the R,R configurations of the chiral carbons in the spacer induce the M helical sense of the ligand, while the S,S configurations induce the P helical sense. Through the comprehensive spectral characterization in combination with semiempirical geometry optimization using the Sparkle/RM1 model, it is confirmed that the preorganized ligands successfully control the homochirality of the helicates. Moreover, the mirror-image CD and CPL spectra and NMR measurements confirm the formation of enantiomeric pairs and their diastereopurities in solution. Detailed photophysical and chiroptical characterization studies reveal that the helicates not only exhibit intense circularly polarized luminescence (CPL) with |glum| values reaching 0.10, but also show a high luminescence quantum yield of 34%. This study effectively combines the helical chirality of the helicates with the excellent sensitization ability of the β-diketones, providing an effective strategy for the syntheses of chiral lanthanide CPL materials.

Enantiospecific Synthesis of (3 R,4 R)-1-Benzyl-4-fluoropyrrolidin-3-amine Utilizing a Burgess-Type Transformation

Manufacture of an EGFR inhibitor required the asymmetric synthesis of a key 3,4-trans-substituted pyrrolidine suitable for pilot-plant scale. The initial synthetic route utilized reagents and intermediates that posed safety concerns due to their energetic potential and then required supercritical fluid chromatography to access the desired single enantiomer. Burgess-type reagents provide tremendous utility in organic synthesis but see limited use on large scales because of their high cost and instability. Nevertheless, extensive process development led to a scale-friendly process where in situ formation of a Boc-Burgess reagent enabled access to a chiral cyclic sulfamate from inexpensive materials. ReactIR monitoring was used to study intermediate stability and enabled processing on a multikilogram scale. The sulfamate was converted to trans-3-fluoro-4-aminopyrrolidine 1 with complete stereospecificity. Intermediate crystallinity offered purity control points where byproducts and impurities were rejected, avoiding the need for chromatography.

Investigation of stereoisomeric bisarylethenesulfonic acid esters for discovering potent and selective PTP1B inhibitors

Protein tyrosine phosphatase 1B (PTP1B) has been considered as a promising therapeutic target for type 2 diabetes mellitus (T2DM) and obesity due to its key regulating effects in insulin signaling and leptin receptor pathways. In this work, a series of cis- and trans-pyrrolidine bisarylethenesulfonic acid esters were prepared and their PTP1B inhibitory potency, selectivity and membrane permeability were evaluated. These novel stereoisomeric molecules especially trans-isomers exhibited remarkable inhibitory activity, significant selectivity as well as good membrane permeability (e.g. compound 28a, IC50 = 120, 1940 and 2670 nM against PTP1B, TCPTP and SHP2 respectively, and Papp = 1.74 × 10?6 cm/s). Molecular simulations indicated that trans-pyrrolidine bisarylethenesulfonic acid esters yielded the stronger binding affinity than their cis-isomers by constructing more interactions with non-catalytic sites of PTP1B. Further biological activity studies revealed that compound 28a could enhance insulin-stimulated glucose uptake and insulin-mediated insulin receptor β (IRβ) phosphorylation with no significant cytotoxicity.

Compound JK-03M having higher protein kinase G inhibitory activity or pharmaceutically acceptable salt thereof and preparation method thereof

The invention discloses a compound which has higher protein kinase G inhibitory activity and is shown in a formula I or pharmaceutically acceptable salt thereof and a preparation method thereof. The compound JK-03M having the higher protein kinase G inhibitory activity comprises a pharmaceutical composition of a new compound and application of the new compound in treatment of pain, in particular to chronic pain. The formula (1) is shown in the description.

Synthesis and α-glucosidase inhibition activity of dihydroxy pyrrolidines

A new series of Deacetylsarmentamide A and B derivatives, amides and sulfonamides of 3,4-dihydroxypyrrolidines as α-glucosidase inhibitors were designed and synthesized. The biological screening test against α-glucosidase showed that some of these compounds have the positive inhibitory activity against α-glucosidase. Saturated aliphatic amides were more potent than the olefinic amides. Among all the compounds, 5o/6o having polar –NH2 group, 10f/11f having polar –OH group on phenyl ring displayed 3–4-fold more potent than the standard drugs. Acarbose, Voglibose and Miglitol were used as standard references. The promising compounds 6i, 5o, 6o, 10a, 11a, 10f and 11f have been identified. Molecular docking simulations were done for compounds to identify important binding modes responsible for inhibition activity of α-glucosidase.

Novel PTP1B enzyme inhibitor, preparation method and applications thereof

The present invention provides a novel PTP1B enzyme inhibitor, a preparation method and applications thereof, and particularly discloses a class of bis 2-substituted ethylene sulfonate compounds and a preparation method thereof, and uses of the bis 2-substituted ethylene sulfonate compounds as the PTP1B enzyme activity inhibitor. According to the present invention, the prepared novel compound has good PTP1B enzyme activity inhibition effect, and has the application value in preparation of drugs for treatment and prevention of diabetes and obesity.