654052-53-6

Upstream product

• 14050-42-1 2,3-Oxidosqualene 
• 111-02-4 2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene 
• 110390-75-5 squalene dibromohydrin: 3,22-dibromo-2,6,10,15,19,23-hexamethyl-6,10,14,18-tetracosatetraen-2,23-diol (all E) 

Downstream Products

• 132905-42-1 (4E,8E,12E,16E)-20,21-epoxy-N,N-dimethyl-4,8,13,17,21-pentamethyl-4,8,12,16-docosatetraenylamine 
• 132905-43-2 22,23-oxidoazasqualene N-oxide 

Relevant academic research and scientific papers

Squalene - Hopene cyclase: Final deprotonation reaction, conformational analysis for the cyclization of (3R,S)-2,3-oxidosqualene and further evidence for the requirement of an isopropylidene moiety both for initiation of the polycyclization cascade and for the formation of the 5-membered E-ring

To provide insight into the polycyclization mechanism of squalene by squalene-hopene cyclase (SHC) from Alicyclobacilus acidocaldarius, some analogs of nor- and bisnorsqualenes were synthesized including the deuterium-labeled squalenes and incubated with the wild-type SHC, leading to the following inferences. (1) The deprotonation reaction for the introduction of the double bond of the hopene skeleton occurs exclusively from the Z-methyl group on the terminal double bond of squalene. (2) 3R-Oxidosqualene was folded in a boat conformation for the A-ring construction, while the 3S-form was in a chair structure. (3) The terminal two methyl groups are indispensable both for the formation of the 5-membered E-ring of the hopene skeleton and for the initiation of the polycyclization cascade, but the terminal Z-methyl group has a more crucial role for the construction of the 5-membered E-ring than the E-methyl group. (4) Some of the novel terpene skeletons, 36,37, 39 and 40. were created from the analogs employed in this investigation.

Synthesis of a deuterated probe for the confocal Raman microscopy imaging of squalenoyl nanomedicines

The synthesis of ω-di-(trideuteromethyl)-trisnorsqualenic acid has been achieved from natural squalene. The synthesis features the use of a Shapiro reaction of acetone-d6 trisylhydrazone as a key step to implement the terminal isopropylidene-d

Production of epoxydammaranes by the enzymatic reactions of (3R)- and (3S)-2,3-squalene diols and those of 2,3:22,23-dioxidosqualenes with recombinant squalene cyclase and the mechanistic insight into the polycyclization reactions

The enzymatic cyclizations of (3R)- and (3S)-2,3-squalene diols by squalene cyclase afforded bicyclic compounds and epoxydamamranes in a ca. 3: 2 ratio. Formation of the epoxydammarane scaffold indicates that a 6/6/6/5-fused tetracyclic cation is involved as the intermediate in the polycyclization reaction. 2,3:22,23-Dioxidosqualenes also afforded an epoxydammarane skeleton, i.e., 3α- or 3β-hydroxyepoxydammaranes, but the amount of bicyclic compounds produced was markedly lower than that of the squalene diols, indicating that the larger steric bulk of the diols had a more significant influence on the polycyclization pathway than the smaller bulk of the expoxide. All the epoxydammaranes had 17R,20R stereochemistry except for one product, demonstrating that these analogs were folded into an all-chair conformation in the reaction cavity. The mechanistic insight into the observed stereochemical specificities indicated that the organized all-chair conformation is rigidly constricted by squalene cyclase and, thus, free conformational change is not allowed inside the reaction cavity; a small rotation of the hydroxyl group or the epoxide toward the intermediary cation gave a high yield of the enzymatic products, while a large rotation led to a low yield of the product. The stereochemistries of the generated epoxydammaranes are opposite to those from natural sources, and thus almost all of the enzymatic products described here are novel. This journal is The Royal Society of Chemistry.

Direct regio- and stereoselective synthesis of squalene 2,3;22,23-dioxide using dioxiranes

Dimethyldioxirane (1a) and its trifluoro analog (1b) were employed to achieve selectively the direct transformation of squalene 2,3(S)-oxide and of squalene 2,3(R)-oxide into the corresponding 2,3(S);22(S),23-dioxide and 2,3(R);22(R),23-dioxide, respectively. These transformations were found to occur with convenient regio- and diastereoselectivity, providing easy access to the valuable dioxides metabolites. The powerful methyl(trifluoromethyl)dioxirane (1b) is the reagent of choice to achieve optimum yields of the target compounds.

Stereoselective syntheses of 1,24-dihydroxy squalene 2,3;22,23-dioxides by double Sharpless epoxidation

A few step synthesis of the (all-E) squalene diol 10 from squalene 4, its double Sharpless epoxidation to the (-)-dihydroxy squalene 2,3;22,23-dioxide 3a, its enantiomer 3b, and the formation of a tetradeutero derivative 12 is described.

Dioxidosqualenes: Characterization and Activity as Inhibitors of 2,3-Oxidosqualene-Lanosterol Cyclase

The preparation and characterization of dioxidosqualenes 4-10 is reported.Treatment of the appropriate epoxysqualene 1,2, or 3 with NBS followed by chromatographic purification afforded the corresponding epoxybromohydrins 11-14 as diastereomeric mixtures, with the exception of compound 11, which could be separated into the respective racemates 11a and 11b.Further dehydrobromination with NaH in THF led to the respective dioxidosqualenes 4-8 in good conversion yields.Dioxides 9 and 10 were isolated from the crude reaction mixture of the treatment of epoxide 2 with dimethyldioxirane.Characterization of compounds 4-10 was carried out by combining 1H and 13C NMR spectral means with positive GC-MS-CI analysis.The GC-MS-CI analysis included the identification of the carbonyl compounds resulting from the cleavage of dioxido derivatives 4-10 with periodic acid.Finally, data on the activity of dioxidosqualenes as oxidosqualene-lanosterol cyclase (OSLC) inhibitors in rat liver microsomes are also presented.In this respect, 2,3:18,19-dioxidosqualene (7) was found to be the best inhibitor within the compounds assayed (IC50=0.11 μM), although dioxides 4,5, and 9 also exhibited a potent inhibitory activity (IC50=21.3, 13.0, and 9.3 μM, respectively).The fact that these compounds could be potentially generated in an organism constitutes a remarkable difference relative to other OSLC inhibitors described to date.

CONVENIENT SYNTHESIS OF CHIRAL EPOXYISOPRENOIDS BY YEAST REDUCTION

The terminal double bond of acyclic isoprenoids was converted into chiral epoxide in high optical yield by using asymmetric reduction of α-ketol with baker's yeast.

Synthesis of Squalenoid Acetylenes and Allenes, as Inhibitors of Squalene Epoxidase

In a search for potential "suicide" inhibitors of squalene epoxidase, a series of mono- and bifunctional squalenoid acetylenes and allenes was synthesized and their inhibitory activity was assayed in preliminary tests.Squalenoid acetylenes were obtained a

Synthesis and biological activity of azasqualenes, bis-azasqualenes and derivatives

Azasqualenes, bis-azasqualenes and derivatives, designed as inhibitors of squalene 2,3-epoxide cyclase, a key enzyme in sterol biosynthesis, were synthesized and their in vitro activities against a variety of yeasts, fungi, gram-positive and gram-negative bacteria were determined.The synthesis involves a new method of squalene degradation, together with an unusual procedure for the aminative reduction of lipophilic aldehydes.A study of the structure-activity relationship was attempted for different biological parameters: anti-bacterial and anti-fungal activities (MIC), inhibition of mycelial growth (GTT), surfactant activity (CMC) and membrane perturbation activity (induction of leakage in liposomes).