74844-91-0

Basic information

• Product Name: N-Boc-trans-4-Hydroxy-L-proline methyl ester
• Synonyms: N-T-BOC-TRANS-4-HYDROXY-L-PROLINE METHYL ESTER;N-(TERT-BUTOXYCARBONYL)-TRANS-HYDROXYL-L-PROLINE METHYL ESTER;N-ALPHA-T-BUTOXYCARBONYL-L-HYDROXYPROLINE METHYL ESTER;N-BOC-TRANS-4-HYDROXYL-L-PROLINE METHYL ESTER;N-BOC-TRANS-4-HYDROXY-L-PROLINE METHYL ESTER;N-BOC-4-HYDROXY-L-PROLINE METHYL ESTER;N-BOC-L-TRANS-4-HYDROXY-PROLINE METHYL ESTER;(2R,4R)-4-HYDROXY-PYRROLIDINE-1,2-DICARBOXYLIC ACID 1-TERT-BUTYL ESTER 2-METHYL ESTER
• CAS NO: 74844-91-0
• Molecular Formula: C₁₁H₁₉NO₅
• Molecular Weight: 245.27
• EINECS: 1592732-453-0
• Product Categories: Amino Acids and Derivatives;Hydroxyproline [Hyp];Unusual Amino Acids;Amino Acids 13C, 2H, 15N;Boc-Amino acid series;Amino Acids & Derivatives;Heterocycles;Peptide Synthesis;Proline Derivatives;Unnatural Amino Acid Derivatives
• Mol File: 74844-91-0.mol

Chemical Properties

• Melting Point: 92-96 °C(lit.)
• Boiling Point: 132°C/0.05mmHg(lit.)
• Flash Point: 156.55 °C
• Appearance: White to light beige/Crystalline Powder
• Density: 1.217 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.501
• Storage Temp.: 2-8°C
• Solubility: Soluble in chloroform, dichloromethane and ethyl acetate.
• PKA: 14.27±0.40(Predicted)
• CAS DataBase Reference: N-Boc-trans-4-Hydroxy-L-proline methyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: N-Boc-trans-4-Hydroxy-L-proline methyl ester(74844-91-0)
• EPA Substance Registry System: N-Boc-trans-4-Hydroxy-L-proline methyl ester(74844-91-0)

Safety Data

• Hazard Codes: Xn
• Statements: 20/21/22-36/37/38
• Safety Statements: 24/25-36-26
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 74844-91-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
N-Boc-trans-4-Hydroxy-L-proline methyl ester is used as an intermediate in the synthesis of various pharmaceutical compounds. Its unique structure allows for the development of new drugs with potential applications in treating different diseases.
Used in Organic Synthesis:
N-Boc-trans-4-Hydroxy-L-proline methyl ester is used as a building block in organic synthesis for the creation of complex molecules. Its functional groups can be selectively modified to produce a wide range of compounds with diverse properties and applications.
Used in Inhibitor Development:
N-Boc-trans-4-Hydroxy-L-proline methyl ester is used as a potential inhibitor of inducible nitric oxide synthase (iNOS), an enzyme involved in various physiological and pathological processes. Inhibiting iNOS can have therapeutic benefits in conditions such as inflammation, pain, and neurodegenerative diseases.
Used in Synthesis of (2S,4R)-4-Hydroxypyrrolidine-1,2-dicarboxylic Acid 1-tert-Butyl Ester 2-Methyl Ester:
N-Boc-trans-4-Hydroxy-L-proline methyl ester is used as a key component in the synthesis of (2S,4R)-4-Hydroxypyrrolidine-1,2-dicarboxylic Acid 1-tert-Butyl Ester 2-Methyl Ester, a compound with potential applications in the pharmaceutical industry.
Used in Synthesis of For-Met-Leu-Phe-OMe (fMLF-OMe) Analogues:
N-Boc-trans-4-Hydroxy-L-proline methyl ester is used in the synthesis of For-Met-Leu-Phe-OMe (fMLF-OMe) analogues, which are based on the replacement of the Met residue by a 4-amino-proline scaffold. These analogues have potential applications in the development of new drugs targeting various biological processes.
Chemical Properties:
N-Boc-trans-4-Hydroxy-L-proline methyl ester is a clear, colorless oil with the molecular formula C10H19NO4. Its chemical properties include the presence of a hydroxyl group, an ester group, and a Boc protecting group, which contribute to its reactivity and versatility in chemical synthesis and pharmaceutical applications.

InChI:InChI=1/C11H19NO5/c1-11(2,3)17-10(15)12-6-7(13)5-8(12)9(14)16-4/h7-8,13H,5-6H2,1-4H3/t7-,8+/m1/s1

Upstream product

• 186581-53-3 diazomethane 
• 13726-69-7 (2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid 
• 24424-99-5 di-tert-butyl dicarbonate 
• 40216-83-9 L-4-hydroxyproline methyl ester hydrochloride 
• 1070-19-5 N-(tert-butyloxycarbonyl) azide 
• 1499-56-5 (R)-4-hydroxy-L-proline ethyl ester 
• 74844-92-1 (2S,4R)-4-Methylsulfanylthiocarboxyoxy-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester 
• 267420-70-2 1-(tert-butyl) 2-methyl (2S,4R)-4-((tert-butyldimethylsilyl)oxy)-5-oxopyrrolidine-1,2-dicarboxylate 
• 67-56-1 methanol 
• 51-35-4 4R-4-hydroxyproline 
• 104241-30-7 (2S,4S)-2-(tert-butoxycarbonyl)amino-4-bromomethyl-γ-butyrolactone 
• 106391-74-6 (2S,4R)-2-(tert-butoxycarbonyl)amino-4-formyl-γ-butyrolactone 
• 104241-31-8 (2S,4S)-2-(tert-butoxycarbonyl)amino-3,4-epoxypentanoic acid methyl ester 
• 77-78-1 dimethyl sulfate 

Downstream Products

• 136024-60-7 1-(tert-butyl) 2-methyl (2S,4R)-4-(benzyloxy)pyrrolidine-1,2-dicarboxylate 
• 84520-67-2 (2S,4R)-4-(methylsulfonyloxy)pyrrolidine-1,2-dicarboxylic acid 1-tert-butylester-2-methylester 
• 168264-15-1 (2S,4S)-4-N³benzoylthymidyl-Boc-prolyl methyl ester 
• 88043-21-4 (2S,4R)-4-(toluene-4-sulfonyloxy)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester 
• 168264-25-3 Boc-(2S,4S)-p-nitrobenzoate-4-hydroxyproline methyl ester 
• 121147-94-2 1-tert-butyl 2-methyl (2S,4S)-4-((benzoyl)oxy)-1,2-pyrrolidinedicarboxylate 
• 93967-75-0 methyl (1-tert-butoxycarbonyl)-(4S)-phenoxy-(2S)-pyrrolidinylcarboxylate 
• 203866-16-4 1-tert-butyl 2-methyl (2S,4S)-4-fluoropyrrolidine-1,2-dicarboxylate 
• 226225-42-9 (2S,4R)-N-tert-butyloxycarbonyl-4-[(tert-butyldiphenylsilyl)oxy]pyrrolidine-2-carboxylic acid methyl ester 
• 169032-99-9 (2S,4S)-4-Chloro-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester 
• 629616-63-3 1-(1,1-dimethylethyl) 2-methyl (2S,4R)-4-{[(4-nitrophenyl)sulfonyl]oxy}-2,3,4,5-tetrahydro-1H-pyrrole-1,2-dicarboxylate 
• 848475-20-7 (4R)-4-[(4'-bromobenzyl)oxy]-N-Boc-L-proline methyl ester 
• 259214-70-5 (2S,4R)-4-(7-Methoxy-2-phenyl-quinolin-4-yloxy)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester 
• 842136-44-1 (2S,4R)-4-(4-Chloro-benzyloxy)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester 

Relevant articles and documents

Construction of Challenging Proline-Proline Junctions via Diselenide-Selenoester Ligation Chemistry

Polyproline sequences are highly abundant in prokaryotic and eukaryotic proteins, where they serve as key components of secondary structure. To date, construction of the proline-proline motif has not been possible owing to steric congestion at the ligatio

Synthesis of Ribo-Azanucleosides by Anodic Oxidation: Reactivity Control of Intermediate for Efficient Access to Pharmacophores

Azanucleosides, the sugar-modified nucleoside analogues, have various biological activities, while their efficient synthetic strategy is still under development. Herein, a novel method for the synthesis of pharmaceutically relevant azanucleosides, β-anomers of ribo-azanucleosides, by means of site-specific anodic C?H activation by using a nitroalkane–lithium perchlorate medium is reported. A mechanistic study of the electrochemical reaction and the armed/disarmed concept from traditional glycochemistry revealed that the 2′-substituent has a significant effect on the reactivity of prolinol derivative, and suitable carboxylic acid additives can control the reactivity of the intermediate species, an iminium cation equivalent. Finally, this method was demonstrated to be applicable for the synthesis of β-anomers of ribo-azanucleosides with all four nucleobases in a stereoselective manner.

C3′-endo-puckered pyrrolidine containing PNA has favorable geometry for RNA binding: Novel ethano locked PNA (ethano-PNA)

A novel peptide nucleic acid (PNA) analogue is designed with a constraint in the aminoethyl segment of the aegPNA backbone so that the dihedral angle β is restricted within 60-80, compatible to form PNA:RNA duplexes. The designed monomer is further functionalized with positively charged amino-/guanidino-groups. The appropriately protected monomers were synthesized and incorporated into aegPNA oligomers at predetermined positions and their binding abilities with cDNA and RNA were investigated. A single incorporation of the modified PNA monomer into a 12-mer PNA sequence resulted in stronger binding with complementary RNA over cDNA. No significant changes in the CD signatures of the derived duplexes of modified PNA with complementary RNA were observed.

A Highly Stereoselective and Scalable Synthesis of l -allo-Enduracididine

A highly stereoselective and scalable synthesis of l-allo-enduracididine from hydroxyproline derivative is described. Pyrrolidine oxidation and reductive ring opening are the key steps in the synthesis. Compared to previously reported approaches, the curr

Design and synthesis of fluorinated peptides for analysis of fluorous effects on the interconversion of polyproline helices

The unique interaction between fluorine atoms has been exploited to alter protein structures and to develop synthetic and analytical applications. To expand such fluorous interaction for novel applications, polyproline peptides represent an excellent molecular nanoscaffold for controlling the presentation of perfluoroalkyl groups on their unique secondary structure. We develop approaches to synthesis fluorinated peptides to systematically investigate how the number, location and types of the fluorous groups on polyproline affect the conformation by monitoring the transition between the two major polyproline structures PPI and PPII. This work provides valuable information on how fluorous interaction affects the peptide structure and also benefits the design of functional fluorous molecules.

Multipodal insulin mimetics built on adamantane or proline scaffolds

Multi-orthogonal molecular scaffolds can be applied as core structures of bioactive compounds. Here, we prepared four tri-orthogonal scaffolds based on adamantane or proline skeletons. The scaffolds were used for the solid-phase synthesis of model insulin mimetics bearing two different peptides on the scaffolds. We found that adamantane-derived compounds bind to the insulin receptor more effectively (Kd value of 0.5 μM) than proline-derived compounds (Kd values of 15–38 μM) bearing the same peptides. Molecular dynamics simulations suggest that spacers between peptides and central scaffolds can provide greater flexibility that can contribute to increased binding affinity. Molecular modeling showed possible binding modes of mimetics to the insulin receptor. Our data show that the structure of the central scaffold and flexibility of attached peptides in this type of compound are important and that different scaffolds should be considered when designing peptide hormone mimetics.

Design, Synthesis, and Biochemical Evaluation of Alpha-Amanitin Derivatives Containing Analogs of the trans-Hydroxyproline Residue for Potential Use in Antibody-Drug Conjugates

Alpha-amanitin, an extremely toxic bicyclic octapeptide extracted from the death-cap mushroom, Amanita phalloides, is a highly selective allosteric inhibitor of RNA polymerase II. Following on growing interest in using this toxin as a payload in antibody-drug conjugates, herein we report the synthesis and biochemical evaluation of several new derivatives of this toxin to probe the role of the trans-hydroxyproline (Hyp), which is known to be critical for toxicity. This structure activity relationship (SAR) study represents the first of its kind to use various Hyp-analogs to alter the conformational and H-bonding properties of Hyp in amanitin.

Synthesis and evaluation of “Ama-Flash”, a photocaged amatoxin prodrug for light-activated RNA Pol II inhibition and cell death

Amanitin is used extensively as a research tool to inhibit RNA Pol II thereby implicating its role in mRNA transcription. Recently, amanitin has gained traction as a toxic payload for targeted therapy. Here we report the first-ever photocaged amanitin analog, that is non-toxic and can be pre-loaded into cells. Light provides a means to inhibit RNA Pol II and provoke cell death on-demand.

VISUAL DETECTION OF PBD INDUCED DNA CROSSLINKS

The present invention relates to the field of oncology, laboratory tools and methods, and especially anti-tumor DNA crosslinking agents. Most patients with advanced solid tumors develop resistance to chemotherapy due to the ability of cancer cells to repair or tolerate sustained DNA damages. The inventors showed that the compounds according to the present invention allow the detection and visualization of alkylated DNA damages induced by PBDs without altering their DNA crosslinking ability. This enables the study of the effect and properties of PBDs. In particular, the present invention relates new derivates of PBD molecules and their synthesis. The present invention also relates to a method for visualizing DNA crosslinking; to a method for assessing the resistance of a tumor to a crosslinking agent and to a method for identifying a molecule or treatment for improving the efficiency of a crosslinking agent.

Quinoline-Proline, Triazole Hybrids: Design, Synthesis, Antituberculosis, Molecular Docking, and ADMET Studies

A series of novel quinoline-proline hybrids (11a-g) and quinoline-proline-1,2,3-triazole hybrids (12-14) were synthesized by click chemistry based on molecular hybridization concept and were characterized by NMR, mass spectrometry, and elemental analysis. All the titled target compounds were tested for antitubercular activity by MABA and LORA methods by in vitro. Interestingly, two compounds (2R,4S)-1-((2-cyclopropyl-4-(4-fluorophenyl)-quinolin-3-yl)-methyl)-4-(4-nitrobenzamido)-N-phenylpyrrolidine-2-carboxamide (11b) and (2R,4S)-1-((2-cyclopropyl-4-(4-fluorophenyl)-quinolin-3-yl)-methyl)-4-(4-fluorobenzamido)-N-phenylpyrrolidine-2-carboxamide (11c) exhibited significant activity against the tested Mycobacterium tuberculosis H37Rv strain. Further, the cytotoxicity (CC50) profile of the titled compounds against the Vero cell was performed and discussed. A molecular docking study of the hit compounds (11b and 11c) was also performed to find their putative binding interaction with the active site of the target proteins. Finally, in silico ADMET properties were also predicted for all the synthesized molecules to evaluate their drug-likeness behavior.