85416-73-5

Usage

Uses

Used in Pharmaceutical Industry:
S-(+)-Rolipram is used as a PDE4 inhibitor for its anti-inflammatory and anti-depressant properties in the central nervous system. Its inhibition of PDE4 enzymes leads to increased levels of cyclic AMP, which in turn modulates various cellular processes and signaling pathways associated with inflammation and depression.
Used in Research Applications:
S-(+)-Rolipram is used as a research tool to study the role of PDE4 enzymes in various biological processes and diseases. Its selectivity for the S isomer allows researchers to investigate the specific effects of PDE4 inhibition in cellular and molecular studies, providing valuable insights into the development of targeted therapies for inflammatory and neuropsychiatric disorders.
Used in Drug Development:
S-(+)-Rolipram serves as a lead compound in the development of new drugs targeting PDE4 enzymes for the treatment of various inflammatory and neuropsychiatric conditions. Its unique properties and selectivity for the S isomer make it an attractive candidate for further optimization and drug design efforts to improve potency, selectivity, and safety profiles.

Biological Activity

Less active enantiomer of the PDE4 inhibitor rolipram (4-(3-(Cyclopentyloxy)-4-methoxyphenyl)pyrrolidin-2-one ).

Upstream product

• 141099-45-8 4-Amino-3-(3-cyclopentyloxy-4-methoxy-phenyl)-butyric acid methyl ester 
• 146426-63-3 (+/-)-1-Benzyl-4-(3-cyclopentyloxy-4-methoxyphenyl)-pyrrolidin-2-one 
• 61413-54-5 Rolipram 
• 137-43-9 Cyclopentyl bromide 
• 37942-01-1 5-bromo-2-methoxyphenol 
• 1001860-35-0 (S)-methyl 3-(3-cyclopentyloxy-4-methoxyphenyl)-4-nitrobutanoate 
• 959799-63-4 ethyl (S)-3-[3-(cyclopentyloxy)-4-methoxyphenyl]-4-phthalimidobutanoate 
• 1259130-31-8 (S)-S-benzyl 3-(3-(cyclopentyloxy)-4-methoxyphenyl)-4-nitrobutanethioate 
• 141332-74-3 2-(cyclopentyloxy)-1-methoxy-4-(2-nitrovinyl)benzene 
• 108-59-8 malonic acid dimethyl ester 
• 1047973-99-8 (S)-3-(3-(cyclopentyloxy)-4-methoxyphenyl)-4-nitrobutanal 
• 138715-51-2 C₁₆H₂₀O₄ 
• 133332-34-0 (E)-3-(3-cyclopentyloxy-4-methoxyphenyl)acrylaldehyde 
• 613-70-7 2-methoxyphenyl acetate 

Downstream Products

• 1295626-74-2 (S)-4-(3-cyclopentyloxy-4-methoxyphenyl)-1-methylpyrrolidin-2-one 

Relevant academic research and scientific papers

Multistep continuous-flow synthesis of (R)- and (S)-rolipram using heterogeneous catalysts

Chemical manufacturing is conducted using either batch systems or continuous-flow systems. Flow systems have several advantages over batch systems, particularly in terms of productivity, heat and mixing efficiency, safety, and reproducibility. However, fo

Enantioselective Flow Synthesis of Rolipram Enabled by a Telescoped Asymmetric Conjugate Addition-Oxidative Aldehyde Esterification Sequence Using in Situ-Generated Persulfuric Acid as Oxidant

A novel approach is reported for the enantioselective flow synthesis of rolipram comprising a telescoped asymmetric conjugate addition-oxidative aldehyde esterification sequence followed by trichlorosilane-mediated nitro group reduction and concomitant la

Enantioselective Synthesis of Pyroglutamic Acid Esters from Glycinate via Carbonyl Catalysis

Direct α-functionalization of NH2-free glycinates with relatively weak electrophiles such as α,β-unsaturated esters still remains a big challenge in organic synthesis. With chiral pyridoxal 5 d as a carbonyl catalyst, direct asymmetric conjugated addition at the α-C of glycinate 1 a with α,β-unsaturated esters 2 has been successfully realized, to produce various chiral pyroglutamic acid esters 4 in 14–96 % yields with 81–97 % ee's after in situ lactamization. The trans and cis diastereomers can be obtained at the same time by chromatography and both of them can be easily converted into chiral 4-substituted pyrrolidin-2-ones such as Alzheimer's drug Rolipram (11) with the same absolute configuration via tert-butyl group removal and subsequent Barton decarboxylation.

Synthesis method of flurolipram

The invention discloses a synthesis method of flurolipram, which comprises the following steps: carrying out catalytic reaction on a compound represented by formula 1 and an alcohol compound represented by formula II by using an N-heterocyclic carbene catalyst to generate an intermediate represented by formula 3.1 and/or 3.2, and carrying out a series of reactions on the intermediate represented by formula 3.1 and/or 3.2 to finally obtain flurolipram.The method is simple to operate, and the substrate is easy to prepare; reaction conditions are mild, and high yield and high stereoselectivity are achieved.

Efficient synthesis of (?)-(R)- and (+)-(S)-rolipram

A novel, efficient and protecting group free enantioselective synthetic approach of (?)-(R)-1 and (+)-(S)-rolipram 2 is described employing the organocatalyzed asymmetric Michael addition, Henry condensation, Wittig olefination and reductive lactamization

Unprecedented hydrophobic amplification in noncovalent organocatalysis "on water": Hydrophobic chiral squaramide catalyzed michael addition of malonates to nitroalkenes

In this study, water was demonstrated to be an exceptionally efficient reaction medium for the noncovalent, hydrogen-bonding-promoted enantioselective Michael addition of malonates to diverse nitroolefins using cinchona-based squaramide catalysts. A significant increase in the reaction rate was observed when the reaction was performed "on water" rather than in the conventional organic solvents, because of the hydrophobic hydration effect. This hydrophobic amplification was significantly dependent upon the hydrophobicity of the C3-substituent (vinyl or ethyl) of cinchona-based catalysts. Thus, the use of more hydrophobic catalyst with an ethyl group at the C3-position, even a highly challenging Michael donor such as dimethyl methylmalonate was also smoothly converted to the desired adduct. Furthermore, because of the remarkable rate acceleration under "on water" conditions, the catalyst loading also significantly decreased. Thus, in the case of β-ketoesters, even 0.01 mol % of catalyst loading was enough to complete the reaction at room temperature, affording the corresponding Michael adducts with perfect diastereo- and enantioselectivity (up to >99:1 d.r., up to 99% ee). The developed "on water" protocol was successfully applied for the scalable syntheses of an antidepressant (S)-rolipram and an anticonvulsant (S)-pregabalin.

METHOD OF PREPARING PHARMACEUTICAL BY CONTINUOUS FLOW MULTI-STAGE REACTION

PROBLEM TO BE SOLVED: To obtain optic active compounds efficiently by incorporating, into a multi-stage flow synthesis system, a column provided with a solid-phase synthesis device necessary for synthesizing optic active compounds to become pharmaceutical

METHOD FOR PREPARING (R)-ROLIPRAM PRECURSOR BY CATALYTIC ENANTIOSELECTIVE MICAHEL REACTION AND METHOD FOR PREPARING (R)-ROLPTRAM USING THE (R)-ROLIPRAM PRECURSOR

According to the present invention, a method for preparing chiral (R)-rolipram precursors includes a step of enabling an asymmetric Michael reaction of 3-(cyclo pentoxy)-4-methoxyphenyl nitro and malonate in the presence of a soluble chiral catalyst. Accordingly, the present invention can synthesize chiral (R)-rolipram precursors at low costs by using an organic catalyst not including transition metals with high optical selectivity and reactivity in the presence of water, aqueous solution, or a mixed solution of an organic solvent which are not harmful to the human body and do not cause environmental pollution.COPYRIGHT KIPO 2015

Multisite organic-inorganic hybrid catalysts for the direct sustainable synthesis of GABAergic drugs

Multisite organic-inorganic hybrid catalysts have been prepared and applied in a new general, practical, and sustainable synthetic procedure toward industrially relevant GABA derivatives. The domino sequence is composed of seven chemical transformations which are performed in two one-pot reactions. The method produces both enantiomeric forms of the product in high enantiopurity as well as the racemate in good yields after a single column purification step. This protocol highlights major process intensification, catalyst recyclability, and low waste generation.

A simple enantioselective route toward (R)- and (S)-Rolipram via anhydride desymmetrization

A highly enantioselective metal-free synthesis of both enantiomers of Rolipram is reported. The key stereoinductive step is a cinchona alkaloid catalyzed opening of a cyclic anhydride prepared from isovanillin, where both enantiomers are available using t