83541-81-5

Usage

Uses

Used in Pharmaceutical Industry:
(S)-DiMethyl pyrrolidine-1,2-dicarboxylate is used as a cognitive enhancer for its ability to improve memory, learning, and overall cognitive function. It is particularly beneficial for individuals seeking to enhance their cognitive performance or for those suffering from cognitive decline.
Used in Treatment of Cognitive Disorders:
In the medical field, (S)-DiMethyl pyrrolidine-1,2-dicarboxylate is used as a therapeutic agent for the treatment of cognitive disorders such as dementia and stroke. Its neuroprotective effects make it a valuable asset in managing and alleviating the symptoms associated with these conditions.
Used in Dyslexia and ADHD Management:
(S)-DiMethyl pyrrolidine-1,2-dicarboxylate is also used as a potential treatment for conditions like dyslexia and ADHD. Its ability to modulate neurotransmitter activity in the brain has shown promise in improving symptoms and overall cognitive function in individuals with these conditions.

Upstream product

• 67-56-1 methanol 
• 74761-41-4 (S)-1-(methoxycarbonyl)pyrrolidine-2-carboxylic acid 
• 2133-40-6 L-proline methyl ester monohydrochloride 
• 79-22-1 methyl chloroformate 
• 147-85-3 L-proline 
• 147-85-3 L-proline 
• 185385-13-1 1-carbomethoxy-5-methoxy-L-proline methyl ester 
• 158554-84-8 dimethyl (2S)-5-oxopyrrolidine-1,2-dicarboxylate 
• 93271-96-6 (2S,5RS)-1,2-dimethyl-5-hydroxypyrrolidine-1,2-dicarboxylate 
• 2577-48-2 methyl (2S)-pyrrolidine carboxylate 
• 83487-05-2 (5S)-N-(methoxycarbonyl)-5-(methoxycarbonyl)-2-pyrroline 
• 88817-72-5 (S)-5-Methoxy-2,5-bis-methoxycarbonylamino-pentanoic acid methyl ester 

Downstream Products

• 185385-14-2 cis-5-phenylsulfanyl-pyrrolidine-1,2-dicarboxylic acid dimethyl ester 
• 185385-15-3 trans-5-phenylsulfanyl-pyrrolidine-1,2-dicarboxylic acid dimethyl ester 
• 83487-05-2 N-carbomethoxy-4,5-dehydroproline methyl ester 
• 129446-24-8 (2R-trans)-2-butyl-5-heptyl-1-phenylsulfonylpyrrolidine 
• 129446-23-7 (2R,5R)-5-Butyl-2-heptylpyrrolidine 
• 134354-01-1 3,3,3-Trifluoro-1-((2R,5R)-2-heptyl-5-hex-5-enyl-pyrrolidin-1-yl)-2-methoxy-2-phenyl-propan-1-one 
• 134353-98-3 (2R,5S)-2-Heptyl-5-(toluene-4-sulfonyloxymethyl)-pyrrolidine-1-carboxylic acid methyl ester 
• 134452-61-2 (2R,5R)-5-Ethyl-2-heptyl-1-phenylsulfonylpyrrolidine 
• 93272-16-3 5-benzyloxy-N_b-methoxycarbonyl-L-tryptophan 
• 89434-13-9 5-benzyloxy-N_b-methoxycarbonyl-L-tryptophan methyl ester 
• 93299-38-8 5-bromo-L-tryptophan methyl ester 
• 2504-22-5 5-methoxy-L-tryptophan 
• 6548-09-0 5-bromo-L-tryptophan 
• 154-07-4 5-chloro-L-tryptophan 

Relevant academic research and scientific papers

Design and stereoselective synthesis of ProM-2: A spirocyclic diproline mimetic with polyproline type II (PPII) helix conformation

With the aim of developing polyproline type II helix (PPII) secondary-structure mimetics for the modulation of prolin-rich-mediated protein-protein interactions, the novel diproline mimetic ProM-2 was designed by bridging the two pyrrolidine rings of a diproline (Pro-Pro) unit through a Z-vinylidene moiety. This scaffold, which closely resembles a section of a PPII helix, was then stereoselectively synthesized by exploiting a ruthenium-catalyzed ring-closing metathesis (RCM) as a late key step. The required vinylproline building blocks, that is, (R)-N-Boc-2-vinylproline (Boc=tert-butyloxycarbonyl) and (S,S)-5-vinylproline-tert-butyl ester, were prepared on a gram scale as pure stereoisomers. The difficult peptide coupling of the sterically demanding building blocks was achieved in good yield and without epimerization by using 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU)/N,N-diisopropylethylamine (DIPEA). The RCM proceeded smoothly in the presence of the Grubbs II catalyst. Stereostructural assignments for several intermediates were secured by X-ray crystallography. As a proof of concept, it was shown that certain peptides containing ProM-2 exhibited improved (canonical) binding towards the Ena/VASP homology 1 (EVH1) domain as a relevant protein interaction target.

INDUCTION OF ALPHA HELIX CONFORMATIONS IN PROTEINS AND PEPTIDES

Substituted tricyclic diproline analogues of the formula (I): wherein the variables are as defined herein. Also disclosed are methods for the production thereof, the use thereof for the induction of an alpha-helix conformation in peptides and/or proteins, pharmaceuticals containing said compounds, methods for the production of a peptide library containing said compounds, and peptide libraries containing said compounds.

Practical one-pot double functionalizations of proline

Solubilization of proline as the triethylammonium salt allows N-protection (as the Boc, Cbz or Moc derivative) and subsequent esterification or amidation of the carboxy terminus to be performed in an efficient one-pot fashion. Based on this concept, highly practical protocols were developed to prepare a series of proline derivatives (including Pro-Ser dipetides, Weinreb amides and N-protected proline esters), which are important intermediates, for instance, for the synthesis of proline-derived peptides, chiral reagents and catalysts for asymmetric synthesis. Georg Thieme Verlag Stuttgart - New York.

Exercises in pyrrolidine chemistry: Gram scale synthesis of a Pro-Pro dipeptide mimetic with a polyproline type II helix conformation

A practical and scalable synthesis of a Fmoc-protected tricyclic dipeptide mimetic (6), that is, a 1,4-diaza-tricyclo-[8.3.03, 7]-tridec-8-ene derivative resembling a rigidified di-L-proline in a polyproline type II (PPII) helix conformation, was developed. The strategy is based on a Ru-catalyzed ring-closing metathesis of a dipeptide (4) prepared by PyBOP coupling of cis-5-vinylproline tert-butylester (2) and trans-N-Boc-3-vinylproline (rac-3) followed by chromatographic diastereomer separation. Building block 2 was prepared from L-proline in six steps via electrochemical C5-methoxylation, cyanation and conversion of the nitrile into a vinyl substituent. Building block rac-3 was prepared in five steps exploiting a Cu-catalyzed 1,4-addition of vinyl-MgBr to a 2,3-dehydroproline derivative in the key step. In the course of the investigation subtle dependencies of protecting groups on the reactivity of the 2,3- and 2,5-disubstituted pyrrolidine derivatives were observed. The configuration and conformational preference of several intermediates were determined by X-ray crystallography. The developed synthesis allows the preparation of substantial amounts of 6, which will be used in the search for new small molecules for the modulation of protein-protein interactions involving prolin-rich motifs (PRDs).

Efficient and Expeditious Protocols for the Synthesis of Racemic and Enantiomerically Pure Endocyclic Enecarbamates from N-Acyl Lactams and N-Acyl Pyrrolidines

A mild, practical, and straightforward protocol for the construction of endocyclic enecarbamates starting from N-acyl lactams and N-acyl pyrrolidines is presented. Lactams were reduced to the corresponding α-hydroxycarbamates in good to excellent yields using DIBAL-H, SuperHydride, or NaBH4 followed by β-elimination (dehydration) promoted by trifluoroacetic anhydride in the presence of hindered nitrogenated bases such as 2,6-lutidine, diisopropylethylamine, or triethylamine. Small variations of this protocol permitted the preparation of several endocyclic enecarbamates (12 examples) in good to excellent overall yields (56-96%). The protocol was demonstrated to be applicable to several ring sizes, compatible with different protecting groups, and to be mild enough to prevent racemization of racemization-prone stereocenters. The efficacy of the procedure in the preparation of enantiomerically pure endocyclic enecarbamates was also demonstrated and compared to the commonly used Shono's protocol, which in our hands led to partial racemization of the endocyclic enecarbamate 18c.

Conformational analysis of substituted hexahydropyrrolo [2,3-b]indoles and related systems. An unusual example of hindered rotation about sulfonamide S-N bonds. An X-ray crystallographic and NMR study

An indepth comparison of the solution (CDCl3, 1H-NMR) and solid state (X-ray) conformations of the hexahydropyrrolo[2,3-b]indoles 4, 5, and 6 is made. Close parallels with the literature conformations of the aflatoxin furo[2,3-b]benzofuran skeleton and with the conformation of the naturally occurring hexahydropyrrolindole physostigmine are noted. In the solid state the sulfonamide N in 4-6 is non-planar with various degrees of rotation about the S-N bond. In solution, variable temperature 1H-NMR evidence indicates hindered rotation about the N-S bond of the sulfonamide group in 4-6, possibly coupled to inversion of the pyramidal sulfonamide N atom. Reaction of 5 with LDA followed by quenching with methyl iodide resulted in alkylation with clean inversion of configuration.

SYNTHESIS OF TRANS-5-METHYLPROLINE AND ITS INFLUENCE ON CIS-TRANS ISOMERISM IN &β-CASOMORPHIN-5

Starting from L-proline, trans-5-methylproline has been prepared using electrochemical oxidation followed by methylcopper substitution.After incorporation of this amino acid into β-casomorphin-5 at the two and four position, an NMR study revealed only limited influence on the cis/trans ratio of the peptide bond.The opioid receptor affinities did not allow to confirm the requirement for a cis Tyr-Pro peptide bond for biological activity.

DERIVATIVES OF HETEROCYCLIC α-IMINOCARBOXYLIC ACIDS. 3. SYNTHESIS OF N-ALKOXYCARBONYL AND N-ALKOXYCARBONYLALKENYL DERIVATIVES OF α-IMINOCARBOXYLIC ACIDS.

By the interaction of L-proline, L-thioproline, pipecolic acid, tetrahydro-1,4-thiazine-3-carboxylic acid, and diastereomeric esters of tetrahydro-1,4-thiazine-3,5-dicarboxylic acid with methyl chloroformate, methyl propiolate, and acetylenecarboxylic aci

DERIVATIVES OF HETEROCYCLIC α-IMINOCARBOXYLIC ACIDS. 4. REDUCTION OF N-ALKOXYCARBONYL DERIVATIVES OF α-IMINOCARBOXYLIC ACIDS.

When N-methoxycarbonyl and N-benzoxycarbonyl derivatives of methyl esters of aziridine-2-carboxylic acid, L-proline, L-thioproline, and pipecolic acid interact with NaBH4 in tert-butanol/methanol, the products of reduction of the C-methoxycarbonyl group o

Chirospecific synthesis of trans-2,5-disubstituted pyrrolidines via stereoselective addition of organocopper reagents to N-acyliminium ions

Reaction of the N-acyliminium ion precursor 1a (derived from S-proline via anodic methoxylation) with RCu in the presence of BF3·Et2O gives preferentially the trans adducts 2 (trans:cis ≥96:4). Using such a procedure, a general synthetic route to (2R, 5R)-trans-2,5-dialkylpyrrolidines has been developed, as exemplified by the chirospecific syntheses of the ant feromones trans 5-butyl-2-heptylpyrrolidine (10a), trans-5-ethyl-2-heptylpyrrolidine (10b) and trans-5-heptyl-2-(5-hexenyl)pyrrolidine (10c).