153650-82-9Relevant articles and documents
Two concise enantioselective total syntheses of (-)-glabrescol implicate alternative biosynthetic pathways starting from squalene
Yang, Peng,Li, Pei-Fang,Qu, Jin,Tang, Liang-Fu
, p. 3932 - 3935 (2012/10/08)
The C2-symmetric (-)-glabrescol was synthesized in two steps from (10S,11R)-dihydroxy-10,11-dihydrosqualene or squalene with 50% or 10% overall yields, respectively. These highly efficient and biomimetic syntheses employed a base-promoted middl
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
Hoshino, Tsutomu,Yonemura, Yukie,Abe, Takamasa,Sugino, Yumi
, p. 792 - 801 (2008/03/27)
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.
Enzymatic cyclizations of squalene analogs with threo- And erythro-diols at the 6,7- or 10,11-positions by recombinant squalene cyclase. Trapping of carbocation intermediates and mechanistic insights into the product and substrate specificities
Abe, Takamasa,Hoshino, Tsutomu
, p. 3127 - 3139 (2007/10/03)
In order to trap the carbocation intermediates formed during the squalene cyclization cascade, squalene analogs with threo- and erythro-dioh at the 6,7- and 10,11-positions were incubated with the recombinant squalene cyclase from Alicyclobacillus acidocaldarius, leading to the construction of the triterpenes with tetrahydropyran, octahydrochromene, decahydronaphthalene with a carbonyl group, dodecahydrobenzo[f]chromene, tetradecahydronaphtho[2,1-b]oxepine and malabaricane skeletons, almost of which are novel compounds. These products indicate that 6-membered monocyclic, 6/6-fused bicyclic and 6/6/5-fused tricyclic cations were involved in the cyclization reaction in addition to acyclic cation. All the trapped cations were the stable tertiary cation, but not the secondary one, indicating that the polycyclization reaction proceeds with a Markovnikov closure. The product profiles revealed that the cyclization reactions proceeded with the product and substrate specificities in addition to enantioselectivity. Mechanistic insight into the observed stereochemical specificities indicated that the pre-organized chair-conformation of squalene-diols is tightly constricted by the cyclase and a free motion or a conformational change is not allowed in the reaction cavity, thus, the substrate and product specificities are dominantly directed by the least motion of the nucleophilic hydroxyl group toward the intermediary carbocation; a small rotation of the hydroxyl group afforded the cyclization products in a good yield, but a large rotation of the hydroxyl group gave a marginal or no detectable amount of products. The Royal Society of Chemistry 2005.
Arylacetic acid derivatization of 2,3- and internal erythro-squalene diols. Separation and absolute configuration determination
Abad, José-Luis,Camps, Francisco
, p. 11519 - 11525 (2007/10/03)
We have studied a new approach for the resolution and absolute configuration determination of the enantiomers of squalene diols as intermediate precursors in the chemical synthesis of different squalene oxides (SOs); (3R)- and (3S)-2,3-SO, (6R,7R)- and (6
Internal Oxidosqualenes: Determination of Absolute Configuration and Activity as Inhibitors of Purified Pig Liver Squalene Epoxidase
Abad, Jose-Luis,Casas, Josefina,Sanchez-Baeza, Francisco,Messeguer, Angel
, p. 3648 - 3656 (2007/10/02)
The preparation and characterization of oxidosqualenes 3-(6R,7R), 3-(6S,7S), 4-(10R,11R), and 4-(10S,11S) is reported.Squalenediol 6 was converted into the corresponding mixture of (R)-Mosher ester 8 and 9, which were separated by semipreparative HPLC.Esters 8 and 9 were reduced to the chiral diols 6-(6R,7S) and 6-(6S,7R), respectively, which were finally converted into the corresponding epoxides 3-(6R,7R) and 3-(6S,7S).A similar procedure was used for the preparation of chiral epoxy derivatives 4-(10R,11R) and 4-(10S,11S) from esters 10 and 11, respectively.The determination of the absolute configuration of these epoxides was carried out by using the method reported by Ohtani et al. (J.Am.Chem.Soc. 1991, 113, 4092), which was adapted to the case of racemic mixtures from synthetic origin.For this purpose, the (R)-Mosher esters derived from the enantiomers of squalendiols 6 or 7 were used.The validity of this approach was confirmed by the absolute configuration found for the threo squalenediols 6-(6R,7R), 6-(6S,7S), 7-(10R,11R), and 7-(10S,11S) formed in the Sharpless asymmetric dihydroxylation of squalene (Crispino, G.A.; Sharpless, K.B.Tetrahedron Lett. 1992, 33, 4273).Results on the inhibitory activity of oxidosqualenes 3-(6R,7R), 3-(6S,7S), 4-(10R,11R), and 4-(10S,11S) using purified squalene epoxidase (SE) from pig liver showed that epoxide 3-(6S,7S) was the best inhibitor within the compounds assayed (IC 50 = 6.7 μM), although oxidosqualene 4-(10R,11R) also exhibited a moderate inhibitory activity (IC 50 = 25μM).The inhibition elicited by the epoxy derivative 3-(6S,7S) was competitive with respect to squalene (Ki = 2.7 μM).This activity is comparable to that reported for the most potent competitive SE inhibitors described so far.Finally, incubation of oxidosqualene 3-(6S,7S) with purified SE led to the formation of dioxidosqualene 22-(3S,6S,7S), whereas its regioisomer 23-(3S,18S,19S) was not detected.In contrast, incubation of epoxide 3-(6R,7R) under the same conditions affored a mixture of dioxides 22-(3S,6R,7R) and 23-(3S,18R,19R) in a 5:12 molar ratio.The fact that oxidosqualenes 3 and 4 have been found in nature, and our previous results showing that racemic dioxide 23 is a potent inhibitor of oxidosqualene-lanosterol cyclase in rat liver microsomes (Abad, J.L.; et al.J.Org.Chem. 1993, 58, 3991), confers a potential physiological relevance to the results reported herein.
Asymmetric dihydroxylation of squalene
Crispino, Gerard A.,Sharpless, K. Barry
, p. 4273 - 4274 (2007/10/02)
The asymmetric dihydroxylation of squalene was studied using the new ligand (DHQD)2-PHAL. Moderate positional selectivity for the 2,3-olefm was observed with high % ee.
