654052-53-6Relevant articles and documents
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
Hoshino, Tsutomu,Nakano, Schin-Ichi,Kondo, Tomohiro,Sato, Tsutomu,Miyoshi, Aya
, p. 1456 - 1470 (2004)
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.
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.
Stereoselective syntheses of 1,24-dihydroxy squalene 2,3;22,23-dioxides by double Sharpless epoxidation
Hauptfleisch, Roland,Franck, Burchard
, p. 383 - 386 (2007/10/03)
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.
