Decane Derivatives Research Articles

Synthesis of 6-oxa-Spiro[4.5]decane Derivatives by Merging Ring-Opening of Benzo[c]oxepines and Formal 1,2-Oxygen Migration.

A facile one-pot synthetic method has been developed for constructing 6-oxa-spiro[4.5]decane skeletons by merging the ring-opening of benzo[c]oxepines and formal 1,2-oxygen migration reactions. More than 30 examples of the 6-oxa-spiro[4.5]decane derivatives have been synthesized under transition-metal-free conditions.

Diastereoselective Synthesis of Dearomatic 2‐oxa‐7‐azaspiro[4.5]decane Derivatives through Gold and Palladium Relay Catalytic Tandem Cyclization of Enynamides with Vinyl Benzoxazinanones

We present a diastereoselective Au/Pd relay catalytic tandem cyclization reaction to produce dearomatic 2‐oxa‐7‐azaspiro[4.5]decane derivatives under mild conditions. This process involves generating furan‐derived azadiene from readily available enynamide, followed by a [2 + 4] cycloaddition with Pd‐π‐allyl dipole decarboxylated from vinyl benzoxazinanone. Our method efficiently constructs the spiro[4.5]decane skeleton, achieving yields ranging from 31‐97% and diastereoselectivities from 6:1 dr to >20:1 dr across 34 examples. This research introduces new cycloaddition sites for azadienes as 1,2‐dipoles and offers a reliable approach for constructing oxa‐azaspiro[4.5]decane frameworks.

Construction of Spiro[4.5]decanes via Annulations of Azadienes with Nazarov Reagent and DFT Studies

AbstractA NaH‐promoted domino reaction between azadiene bearing an indene moiety with Nazarov reagent was developed. A variety of spiro[4.5]decane derivatives were obtained via [4+2] cycloaddition with good yields and high diastereoselectivity. The domino strategy benefited from mild reaction conditions and very broad substrate scope. Furthermore, a gram‐scale experiment and a transformation of the product were carried out. Lastly, density functional theory (DFT) calculations have been performed to verify the proposed reaction mechanism and analyze the observed diastereoselectivity.

1,3,8-Triazaspiro[4.5]decane Derivatives Inhibit Permeability Transition Pores through a FO-ATP Synthase c Subunit Glu119-Independent Mechanism That Prevents Oligomycin A-Related Side Effects

Permeability transition pore (PTP) molecular composition and activity modulation have been a matter of research for several years, especially due to their importance in ischemia reperfusion injury (IRI). Notably, c subunit of ATP synthase (Csub) has been identified as one of the PTP-forming proteins and as a target for cardioprotection. Oligomycin A is a well-known Csub interactor that has been chemically modified in-depth for proposed new pharmacological approaches against cardiac reperfusion injury. Indeed, by taking advantage of its scaffold and through focused chemical improvements, innovative Csub-dependent PTP inhibitors (1,3,8-Triazaspiro[4.5]decane) have been synthetized in the past. Interestingly, four critical amino acids have been found to be involved in Oligomycin A-Csub binding in yeast. However, their position on the human sequence is unknown, as is their function in PTP inhibition. The aims of this study are to (i) identify for the first time the topologically equivalent residues in the human Csub sequence; (ii) provide their in vitro validation in Oligomycin A-mediated PTP inhibition and (iii) understand their relevance in the binding of 1,3,8-Triazaspiro[4.5]decane small molecules, as Oligomycin A derivatives, in order to provide insights into Csub interactions. Notably, in this study we demonstrated that 1,3,8-Triazaspiro[4.5]decane derivatives inhibit permeability transition pores through a FO-ATP synthase c subunit Glu119-independent mechanism that prevents Oligomycin A-related side effects.

Alkylidene Meldrum's Acids as Platforms for the Vinylogous Synthesis of Dihydropyranones.

Upon Brønsted base organocatalysis, ketone-derived alkylidene Meldrum's acids proved to be competent vinylogous platforms able to undergo a formal (4+2) cycloaddition reaction with dihydro-2,3-furandione, providing an unprecedented route to 3,6-dihydropyran-2-ones as spiro[4.5]decane derivatives with up to 98 % ee thanks to the commercially available Takemoto catalyst. Preliminary investigation showed that this reaction could be extended to other activated ketones, establishing these alkylidene Meldrum's acids as a novel C4-synthon in the vinylogous series.

Alkylidene Meldrum's Acids as Platforms for the Vinylogous Synthesis of Dihydropyranones

AbstractUpon Brønsted base organocatalysis, ketone‐derived alkylidene Meldrum's acids proved to be competent vinylogous platforms able to undergo a formal (4+2) cycloaddition reaction with dihydro‐2,3‐furandione, providing an unprecedented route to 3,6‐dihydropyran‐2‐ones as spiro[4.5]decane derivatives with up to 98 % ee thanks to the commercially available Takemoto catalyst. Preliminary investigation showed that this reaction could be extended to other activated ketones, establishing these alkylidene Meldrum's acids as a novel C4‐synthon in the vinylogous series.

A naturally occurring mutation in ATP synthase subunit c is associated with increased damage following hypoxia/reoxygenation in STEMI patients.

Preclinical models of ischemia/reperfusion injury (RI) demonstrate the deleterious effects of permeability transition pore complex (PTPC) opening in the first minutes upon revascularization of the occluded vessel. The ATP synthase c subunit (Csub) influences PTPC activity in cells, thus impacting tissue injury. A conserved glycine-rich domain in Csub is classified as critical because, when mutated, it modifies ATP synthase properties, protein interaction with the mitochondrial calcium (Ca2+) uniporter complex, and the conductance of the PTPC. Here, we document the role of a naturally occurring mutation in the Csub-encoding ATP5G1 gene at the G87 position found in two ST-segment elevation myocardial infarction (STEMI) patients and how PTPC opening is related to RI in patients affected by the same disease. We report a link between the expression of ATP5G1G87E and the response to hypoxia/reoxygenation of human cardiomyocytes, which worsen when compared to those expressing the wild-type protein, and a positive correlation between PTPC and RI.

2-Oxaspiro[4.5]decane and α-pyrenocine derivatives from the endophytic fungus Roussoella sp. PSU-H51

One new 2-oxaspiro[4.5]decane, roussoellide, and one new α-pyrenocine, 2',3'-dihydropyrenocine A, together with nine known compounds including known arthropsolide A, and pyrenocines A and E, were obtained from the culture broth of the endophytic fungus Roussoella sp. Their structures were determined using spectroscopic data. The absolute configuration of known arthropsolide A was assigned on the basis of X-ray diffraction data using Cu Kα radiation. Known pyrenocine A displayed weak cytotoxic activity against breast cancer (MCF-7) cells with an IC50 value of 27.1 µM and weak antifungal activity against Microsporum gypseum SH-MU-4 with an MIC value of 615.2 µM.

Selective cloud point extraction of thorium (IV) using tetraazonium based ionic liquid

This study involves the synthesis and characterization of a new tetra-cationic surface-active ionic liquid (SAIL) based on tetraazonia-tricyclo[3.3.1.13,7]decane derivative. The surface properties of the synthesized SAIL revealed good surface activity, self-aggregation and clouding ability indicating its feasibility in surfactant-mediated extraction applications. Applying the synthesized SAIL combined with Triton X-100 as a mixed surfactant system in cloud point extraction of Th(IV) ions resulted in a sensitive and selective extraction procedure. Arsenazo III was used as Th(IV) chelating agent and the pre-concentrated chelate was spectrophotometrically determined. The main variables affecting the extraction efficiency were systematically investigated. The highest extraction efficiency was achieved at pH 5.0 with 2.5 × 10−3 mol L-1 SAIL and 1.0 % (v/v) Triton X-100. At the optimized conditions, the developed method exhibited a linear working range from 10.0 to 100.0 ng mL-1 with a detection limit of 77.0×10-2 ng mL−1. The interfering impact of various ions on Th(IV) extraction efficiency was evaluated. The applicability and reliability of the developed method were evaluated by determining Th(IV) at trace levels in various water samples and the obtained recovery values were ranging from 98.0 to 101.4%. The developed CPE method is sensitive, simple, reliable and consistent with the green chemistry principles.

Synthesis and evaluation of new 1-oxa-8-azaspiro[4.5]decane derivatives as candidate radioligands for sigma-1 receptors

We report the design, synthesis, and evaluation of a series of 1-oxa-8-azaspiro[4.5]decane and 1,5-dioxa-9-azaspiro[5.5]undecane derivatives as selective σ1 receptor ligands. All seven ligands exhibited nanomolar affinity for σ1 receptors (Ki(σ1) = 0.47 – 12.1 nM) and moderate selectivity over σ2 receptors (Ki(σ2)/ Ki(σ1) = 2 – 44). Compound 8, with the best selectivity among these ligands, was selected for radiolabeling and further evaluation. Radioligand [18F]8 was prepared via nucleophilic 18F-substitution of the corresponding tosylate precursor, with an overall isolated radiochemical yield of 12–35%, a radiochemical purity of greater than 99%, and molar activity of 94 – 121 GBq/μmol. Biodistribution studies of [18F]8 in mice demonstrated high initial brain uptake at 2 min. Pretreatment with SA4503 resulted in significantly reduced brain-to-blood ratio (70% − 75% at 30 min). Ex vivo autoradiography in ICR mice demonstrated high accumulation of the radiotracer in σ1 receptor-rich brain areas. These findings suggest that [18F]8 could be a lead compound for further structural modifications to develop potential brain imaging agents for σ1 receptors.

Gas chromatography-mass- spectroscopy analysis of bioactive compounds from Streptomyces spp. isolated from Tigris river sediments in Baghdad city

Background:The Streptomyces are considered the most important bacterial source for bioactive compounds production including natural antibiotics. 
 Objective: This study focused on analysis of these products to characterize the most active substances which may contain new antibiotics. 
 Materials and methods: Samples with the highest antibacterial activities (21, M5, N- and D-) were chosen from a previous study after secondary screening for the intracellular (biomass) extract which showed more antagonism efficiency than that observed in extracellular crude extract.Gas chromatography – mass spectroscopy (GC-MS) was preformed to detect the structure of the compounds in intracellular crude extracts in these isolates. 
 Results: The GC-MS analysis showed a total of 49 peaks observed in 4 isolates, isolate M5=14 peaks, isolate D=11peaks, isolate N= 20 peaks and isolate 21= 4peaks. Isolate D-, which showed the highest zone of inhibition in secondary screening than that in other isolates, is associated with the most prevalence active compounds like the Decane derivatives, in addition to Triadimenol; Azetidine, 1-(1,1-dimethylethyl)-3-methyl; Hexanoic acid, 2-ethyl-, 2-ethylhexyl ester and 3,3,7,7-Tetramethyl-1,5-diazabicyclo(3.3.0)octane. While isolate 21, has less peaks in comparing with the other samples, with great occurrence in components: 1-Dimethylaminohexane with molecular formula C8H19N and molecular weight 129 and Propamocarb with molecular formula C9H20N2O2 and molecular weight 188, in addition to many volatile organic compounds. The greatest components of isolate M5 were Triadimenol and 3,3,7,7-Tetramethyl-1,5-diazabicyclo(3.3.0)octane, in addition to the presence of Decane derivatives; amine compounds and Vitamin E. Isolate N- showed a great occurrence with components Triadimenol and Azetidine, 1-(1,1-dimethylethyl)-3-methyl-with a molecular formula C8H17N and with a molecular weight 127; also the presence of an important component Hexanoic acid, 2-methyl- with the molecular formula C7H14O2 and with molecular weight 103 which has been considered as an essential component of muramycin antibiotic; compounds which contain Benzene ring. 
 Conclusion: The most prominent compounds detected in the selected isolates by using GC-MS technique were Decane derivatives and Triadimenol.

Facile access to diverse all-carbon quaternary center containing spirobicycles by exploring a tandem Castro-Stephens coupling/acyloxy shift/cyclization/semipinacol rearrangement sequence.

Efficient combination of two or more reactions into a practically useful purification free sequence is of great significance for the achievement of structural complexity and diversity, and an important approach for the development of new synthetic strategies that are industrially step-economic and environmentally friendly. In this work, a facile and efficient method for the construction of highly functionalized spirocyclo[4.5]decane derivatives containing a synthetically challenging quaternary carbon center has been successfully developed through the realization of a tandem Castro–Stephens coupling/1,3-acyloxy shift/cyclization/semipinacol rearrangement sequence. Thus a series of multi-substituted spirocyclo[4.5]decane and functionalized cyclohexane skeletons with a phenyl-substituted quaternary carbon center have been constructed using this method as illustrated by 24 examples in moderate to good yields. The major advantages of this method over the known strategies are better transformation efficiency (four consecutive transformations in one tandem reaction), product complexity and diversity. As a support of its potential application, a quick construction of the key tetracyclic diterpene skeleton of waihoensene has been achieved.

Cp*Co(III)-Catalyzed Dearomative [3 + 2] Spiroannulation of 2-Alkenylphenols with Ynamides via C-H Activation.

An oxidative [3 + 2] C-H spiroannulation reaction of 2-alkenylphenols with ynamides has been developed toward the synthesis of spiro[4,5]decane derivatives. This dearomative reaction employs earth-abundant cobalt as the metal catalyst and occurs under rather mild reaction conditions (room temperature). The use of ynamides confers unique reactivity and exclusive regioselectivity. The products bearing an all-carbon quaternary stereogenic center were constructed in generally good yields with good functional group tolerance being observed. Experimental mechanistic studies were conducted, and a possible reaction mechanism is proposed.

Synthesis of Tricyclo[4.4.0.02,7]decane Derivatives from Tricyclo[4.1.0.02,7]heptane Precursors

Tricyclo[4.1.0.02,7]heptane and 1-phenyltricyclo[4.1.0.02,7]heptane reacted with 2,3-bis(benzenesulfonyl)propene in boiling toluene (20–24 h) in the presence of benzoyl peroxide via trans-selective cleavage of the C1–C7 central bicyclobutane bond to give 6(7)-syn-benzenesulfonyl-7(6)-exo-[2-(benzenesulfonyl)prop-2-en-1-yl]bicyclo[3.1.1]heptane derivatives. The latter underwent cyclization to 1,9- and 7,9-bis(benzenesulfonyl)tricyclo[4.4.0.02,7]decane derivatives by the action of potassium tert-butoxide in dioxane at 50°C as a result of intramolecular Michael addition. Heating of the cyclization products in dioxane at 100°C in the presence of potassium tert-butoxide resulted in elimination of benzenesulfinic acid molecule with the formation of mixtures of two isomeric benzenesulfonyl-substituted tricyclo[4.4.0.02,7]dec-3-enes.

Synthesis and Prediction of the Ubiquinol‐cytochrome c Reductase Inhibitory Activity of 3,4‐Dihydroisoquinolines and 2‐Azaspiro[4.5]decanes (Spiropyrrolines)

Isoquinolines rank as the second largest group among the plant alkaloids. Natural isoquinolines and synthetic isoquinoline derivatives exhibit numerous biological activities. In this study, the approaches to synthesis of new 3,4‐dihydroisoquinoline and 2‐azaspiro[4.5]decane (spiropyrroline) derivatives annelated by C(3)─C(4) bonds with a cyclohexyl or cyclopentyl moiety have been developed. In accord with the results of biological activity prediction by the pass software, molecular docking was carried out on the ubiquinol‐cytochrome c reductase (bc1 complex) model. Compounds 6e and 12a,d were found out as potential Q0 site inhibitors of the bovine bc1 complex.

Phosphine-Catalyzed [8 + 2]-Annulation of Heptafulvenes with Allenoates and Its Asymmetric Variant: Construction of Bicyclo[5.3.0]decane Scaffold.

In this paper, a phosphine-catalyzed [8 + 2]-annulation of heptafulvene with allenoates has been achieved under mild conditions, giving functionalized bicyclo[5.3.0]decane derivatives in moderate to excellent yields. Using chiral phosphine as the catalyst, optically active products were obtained in moderate to high yields with excellent enantioselectivities.

Synthetic studies on psiguadial B: Construction of bicyclo[4.3.1]decane skeleton via double cyclization reaction of alkyne dicobalt complex

A new method for constructing the polycyclic skeleton of psiguadial B (1), a meroterpenoid isolated from an evergreen shrub of Myrtaceae, was developed. The terpenoid substructure of 1 was constructed on the basis of a cascade double cyclization reaction of an alkyne dicobalt complex, which afforded the bicyclo[4.3.1]decane derivative having a benzyl group with the correct configuration. The substituted aromatic ring was introduced to the bridgehead position of the intermediate, and bromination under radical conditions followed by intramolecular cyclization reaction resulted in formation of the benzopyran moiety in a stereoselective manner.

Synthesis and Anticancer Activity of New 1-Thia-4-azaspiro[4.5]decane, Their Derived Thiazolopyrimidine and 1,3,4-Thiadiazole Thioglycosides.

New 1-thia-azaspiro[4.5]decane derivatives, their derived thiazolopyrimidine and 1,3,4-thiadiazole compounds were synthesized. The thioglycoside derivatives of the synthesized (1,3,4-thiadiazolyl)thiaazaspiro[4.5]decane and thiazolopyrimidinethione compounds were synthesized by glycosylation reactions using acetylated glycosyl bromides. The anticancer activity of synthesized compounds was studied against the cell culture of HepG-2 (human liver hepatocellular carcinoma), PC-3 (human prostate adenocarcinoma) and HCT116 (human colorectal carcinoma) cell lines and a number of compounds showed moderate to high inhibition activities.

Synthesis, biological evaluation and molecular modeling of 1-oxa-4-thiaspiro- and 1,4-dithiaspiro[4.5]decane derivatives as potent and selective 5-HT1A receptor agonists

Recently, 1-(1,4-dioxaspiro[4,5]dec-2-ylmethyl)-4-(2-methoxyphenyl)piperazine (1) was reported as a potent 5-HT1AR agonist with a moderate 5-HT1AR selectivity. In an extension of this work a series of derivatives of 1, obtained by combining different heterocyclic rings with a more flexible amine chain, was synthesized and tested for binding affinity and activity at 5-HT1AR and α1 adrenoceptors. The results led to the identification of 14 and 15 as novel 5-HT1AR partial agonists, the first being outstanding for selectivity (5-HT1A/α1d = 80), the latter for potency (pD2 = 9.58) and efficacy (Emax = 74%). Theoretical studies of ADME properties shows a good profile for the entire series and MDCKII-MDR1 cells permeability data predict a good BBB permeability of compound 15, which possess a promising neuroprotective activity. Furthermore, in mouse formalin test, compound 15 shows a potent antinociceptive activity suggesting a new strategy for pain control.

ChemInform Abstract: Rhodium‐Catalyzed [4 + 3] Cycloaddition to Furans: Direct Access to Functionalized Bicyclo[5.3.0]decane Derivatives.

AbstractA novel access to fused 5/7 ring systems through rhodium‐catalyzed [4 + 3] cycloaddition of mono‐ and disubstituted furans to cyclic donor‐acceptor diazocarboxylate (II) is described.