Discovery of highly potent analgesic activity of isopulegol-derived (2R,4aR,7R,8aR)-4,7-dimethyl-2-(thiophen-2-yl)octahydro-2H-chromen-4-ol

Nazimova, E. V.; Павлова, А. В.; Mikhalchenko, Oksana S.; Ильина, И. В.; Корчагина, Д. В.; Толстикова, Т. Г.; Волчо, К. П.; Salakhutdinov, N. F.

doi:10.1007/s00044-016-1573-3

Cited by 45 publications

(38 citation statements)

References 24 publications

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“…It is known that compounds with a chromene (benzopyran) scaffold have a broad spectrum of biological activity . A high pharmaceutical potential and low toxicity of these substances resulted in a considerable interest in the synthesis of new chromene derivatives . Recently, it has been shown, that in catalytic condensation of a natural allyl alcohol (−)‐isopulegol (I) with aldehydes, substituted octahydro‐2 H ‐chromen‐4‐ol (III) as 4 R ‐ and 4 S ‐diastereomers was formed along with a dehydration product IV (Scheme ).…”

Section: Methodsmentioning

confidence: 99%

“…Recently, it has been shown, that in catalytic condensation of a natural allyl alcohol (−)‐isopulegol (I) with aldehydes, substituted octahydro‐2 H ‐chromen‐4‐ol (III) as 4 R ‐ and 4 S ‐diastereomers was formed along with a dehydration product IV (Scheme ). Different catalysts such as I 2 , p ‐toluenesulfonic acid, BF 3 ⋅Et 2 O, zeolites, clays were used in this reaction . A relatively high 4 R /4 S ratio (9.0) with overall yields of 70–88 % were observed in condensation of isopulegol (obtained by cyclization of R ‐citronellal) with aromatic aldehydes at −78 °C using scandium triflate .…”

Section: Methodsmentioning

confidence: 99%

“…Some synthesized octahydro‐2 H ‐chromen‐4‐ols on the basis of isopulegol display a pronounced physiological activity . Thus, 4 R ‐diastereomer obtained by the reaction of I with thiophene‐2‐carbaldehyde on K‐10 clay exhibited in vivo prolonged analgesic effect surpassing that of Diclofenac .…”

Section: Methodsmentioning

confidence: 99%

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Acid‐modified Halloysite Nanotubes as a Stereoselective Catalyst for Synthesis of 2H‐Chromene Derivatives by the Reaction of Isopulegol with Aldehydes

et al. 2018

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Acid-modified halloysite nanotubes were used for the first time as a stereoselective catalyst for synthesis of oxygen-containing heterocycles applying of allyl alcohol (À)-isopulegol condensation with aldehydes to the octahydro-2H-chromenol (4R-and 4S-diastereomers) as an example. The catalysts were characterized by XRF, XRD, N 2 -adsorption, FTIR with pyridine and MAS NMR methods. A high ratio of 4R/4S diastereomers (7.6-14.5) under mild conditions in cyclohexane was considerably exceeding previously reported results. Unprecedented selectivity (79-83 %) to 4R isomer of thiophenyl-substituted chromenol exhibiting high analgesic activity was achieved. An increase in stereoselectivity with a decrease in the halloysite drying temperature and catalyst acidity clearly indicates formation of 4R diastereomer on the weak Brønsted sites. This work is an example that control of the stereoselectivity of acid-catalyzed organic reactions can be effectively carried out by varying water content on the aluminosilicate surface. Modified halloysite nanotubes can be considered as extremely promising catalysts for stereoselective synthesis of heterocyclic compounds.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Acid‐modified Halloysite Nanotubes as a Stereoselective Catalyst for Synthesis of 2H‐Chromene Derivatives by the Reaction of Isopulegol with Aldehydes

et al. 2018

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“…Key intermediate (-)-3-methylenetetrahydrofuran 3 was prepared from commercially available (-)-isopulegol 1 by oxidizing its hydroxyl function, followed by the stereoselective reduction of the resulting carbonyl group, thus providing (+)-neoisopulegol 2 [48][49][50][51]. The allylic chlorination of (+)neoisopulegol 2 was followed by the cyclization-produced (-)-methylenetetrahydrofuran 3 [52][53][54][55], which was transformed into (−)-methylenetetrahydrofuran 4 by allylic oxidation after applying the literature method [55,56] (Figure 1).…”

Section: Synthesis Of Key Intermediatementioning

confidence: 99%

“…Synthesis of (-)-isopulegol-based methylenetetrahydrofuran 3: (i) PCC (2 equivalents), DCM (Dichloromethane), 25 °C, 48 h, 80% than L-selectride (1.5 equivalents) dry THF, −78 °C, 1 h, 90% [48][49][50][51]…”

Section: Figurementioning

confidence: 99%

Synthesis and Application of 1,2-Aminoalcohols with Neoisopulegol-Based Octahydrobenzofuran Core

et al. 2019

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A library of 1,2-aminoalcohol derivatives with a neoisopulegol-based octahydrobenzofuran core was developed and applied as chiral catalysts in the addition of diethylzinc to benzaldehyde. The allylic chlorination of (+)-neoisopulegol, derived from natural (-)-isopulegol followed by cyclization, gave the key methyleneoctahydrobenzofuran intermediate. The stereoselective epoxidation of the key intermediate and subsequent oxirane ring opening with primary amines afforded the required 1,2-aminoalcohols. The ring closure of the secondary amine analogues with formaldehyde provided spiro-oxazolidine ring systems. The dihydroxylation of the methylenetetrahydrofuran moiety with OsO 4 /NMO (4-methylmorpholine N-oxide) resulted in the formation of a neoisopulegol-based diol in a highly stereoselective reaction. The antimicrobial activity of both the aminoalcohol derivatives and the diol was also explored. Molecules 2020, 25, 21 2 of 14 antimalarial [26-28], and antileishmanial [29] agents. The 1,2-aminoalcohol function is found in a broad range of β-adrenergic blockers that are used extensively in the management of cardiovascular disorders [30], including hypertension, angina pectoris and cardiac arrhythmias, and other disorders that are related to the sympathetic nervous system [31,32]. 1,2-aminoalcohols have also been demonstrated to be excellent chiral auxiliaries and chiral catalysts in asymmetric synthesis [33]. To achieve new, efficient, and commercially available chiral catalysts, natural chiral terpenes, such as α-pinene [34-38], β-pinene [34,39], (-)-3-carene [39,40], (-)-verbenone [41,42], (-)-fenchone [43,44], (+)-camphor [43,45,46], and (-)-menthone [47] have proven to be excellent sources for the synthesis of bifunctional chiral compounds and heterocycles.In the present work, we set out to create a compound library with a (+)-neoisopulegol-based octahydrobenzofuran core and 1,2-aminoalcohol moieties. The synthesis started from commercially available (-)-isopulegol and then utilizing the resulting 1,2-aminoalcohol derivatives as chiral catalysts in the enantioselective addition of diethylzinc to benzaldehyde. Furthermore, the antimicrobial activities of the synthesized compounds were also tested on multiple bacterial and fungal strains. Results Synthesis of Key Intermediate 3Key intermediate (-)-3-methylenetetrahydrofuran 3 was prepared from commercially available (-)-isopulegol 1 by oxidizing its hydroxyl function, followed by the stereoselective reduction of the resulting carbonyl group, thus providing (+)-neoisopulegol 2 [48][49][50][51]. The allylic chlorination of (+)-neoisopulegol 2 was followed by the cyclization-produced (-)-methylenetetrahydrofuran 3 [52-55], which was transformed into (−)-methylenetetrahydrofuran 4 by allylic oxidation after applying the literature method [55,56] (Figure 1).

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Corymbia citriodora: A Valuable Resource from Australian Flora for the Production of Fragrances, Repellents, and Bioactive Compounds

Goodine

Oelgemöller

2020

ChemBioEng Reviews

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As global chemical manufacturing has historically relied on inexpensive feedstocks from the petrochemical industry, the identification of new naturally derived feedstocks represents an important and sustainable alternative. This review introduces Corymbia citriodora (Hook.) K.D.Hill & L.A.S.Johnson as an attractive renewable resource of natural compounds for organic chemical transformations. Although native to Australia, this plant species is now grown and harvested worldwide. The chemical composition of citriodora oils varies with location, harvesting season and age of leaves. Beyond their historic uses as fragrances or repellents, the more abundant terpenes found in citriodora oils such as citronellal, citronellol, and isopulegol have notable roles in the manufacture of fine chemicals. This review highlights several industrial processes intimately related to the citriodora terpenes, some advances in fragrances and repellents, as well as the use of these terpenes in the most recently reported synthesis of bioactive compounds. Where relevant, processes highlighting the adoption of green chemistry principles are presented and briefly discussed.

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Discovery of highly potent analgesic activity of isopulegol-derived (2R,4aR,7R,8aR)-4,7-dimethyl-2-(thiophen-2-yl)octahydro-2H-chromen-4-ol

Cited by 45 publications

References 24 publications

Acid‐modified Halloysite Nanotubes as a Stereoselective Catalyst for Synthesis of 2H‐Chromene Derivatives by the Reaction of Isopulegol with Aldehydes

Acid‐modified Halloysite Nanotubes as a Stereoselective Catalyst for Synthesis of 2H‐Chromene Derivatives by the Reaction of Isopulegol with Aldehydes

Synthesis and Application of 1,2-Aminoalcohols with Neoisopulegol-Based Octahydrobenzofuran Core

Corymbia citriodora: A Valuable Resource from Australian Flora for the Production of Fragrances, Repellents, and Bioactive Compounds

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