- β-Amyrin Biosynthesis: Effect of Steric Bulk at the 6-, 10- and 15-Positions in the 2,3-Oxidosqualene Backbone on Polycyclisation Cascades
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β-Amyrin synthase incubation experiments have been conducted to determine the influence of steric effects at the 6-, 10- and 15-positions of 2,3-oxidosqualene on the polycyclisation pathway. Nor- and ethyl-substituted oxidosqualene analogues were synthesised. Cyclisation of the ethyl-substituted analogues did not occur, but the nor analogues underwent a polycyclisation cascade to yield fully cyclised products with 6/6/6/6/6-fused pentacyclic scaffolds generated via a final oleanyl cation. Previously, we reported that 19- and 23-ethyl-substituted analogues underwent polycyclisation reactions. Therefore, the catalytic domain involved in earlier cyclisation steps is notably compact. In contrast, the catalytic domain in the later cyclisation steps is more loosely packed (less compact) to accommodate the bulky ethyl group. The reaction cavities for recognising branched methyl groups are discussed by comparing β-amyrin synthase with other triterpene cyclases such as lanosterol and hopene synthases.
- Terasawa, Yuri,Sasaki, Yusuke,Yamaguchi, Yuki,Takahashi, Kazunari,Hoshino, Tsutomu
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supporting information
p. 287 - 295
(2017/01/24)
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- Lanosterol biosynthesis: The critical role of the methyl-29 group of 2,3-oxidosqualene for the correct folding of this substrate and for the construction of the five-membered D ring
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Lanosterol synthase catalyzes the polycyclization reaction of (3S)-2,3-oxidosqualene (1) into tetracyclic lanosterol 2 by folding 1 in a chair-boat-chair-chair conformation. 27-Nor- and 29-noroxidosqaulenes (7 and 8, respectively) were incubated with this enzyme to investigate the role of the methyl groups on 1 for the polycyclization cascade. Compound 7 afforded two enzymatic products, namely, 30-norlanosterol (12) and 26-normalabaricatriene (13; 12/13 9:1), which were produced through the normal chair-boat-chair-chair conformation and an atypical chair-chair-boat conformation, respectively. Compound 8 gave two products 14 and 15 (14/15 4:5), which were generated by the normal and the unusual polycyclization pathways through a chair-chair-boat-chair conformation, respectively. It is remarkable that the twist-boat structure for the B-ring formation was changed to an energetically favored chair structure for the generation of 15. Surprisingly, 14 and 15 consisted of a novel 6,6,6,6-fused tetracyclic ring system, thus differing from the 6,6,6,5-fused lanosterol skeleton. Together with previous results, we conclude that the methyl-29 group is critical to the correct folding of 1, with lesser contributions from the other branched methyl groups, such as methyl-26, -27, and -28. Furthermore, we demonstrate that the methyl-29 group has a crucial role in the formation of the five-membered D ring of the lanosterol scaffold. Ringing in the changes: The incubation of 1 with porcine-liver cyclase afforded new nortriterpenes 2 and 3 with 6,6,6,6-fused tetracyclic skeletons, which were produced by chair-boat-chair-chair and chair-chair-boat-chair conformations, respectively (see scheme), thus indicating that the 29-methyl group is critical to the correct folding of oxidosqualene and to the formation of the five-membered D ring for lanosterol biosynthesis. Copyright
- Hoshino, Tsutomu,Chiba, Akifumi,Abe, Naomi
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supporting information
p. 13108 - 13116
(2013/01/15)
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- Total synthesis of polyprenylhydroquinols and benzoquinones
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The total synthesis of polyprenylhydroquinols and benzoquinones is described.First, two appropriate aromatic allyl carbonates (moieties with one and two prenyls) and two activated bifunctional terpenyl derivatives (moieties with two and three prenyls) were synthesized.These molecules were then reacted together using a highly regio- and stereoselective coupling with Pd(PPh3)4 as a catalyst.The synthesis was achieved by functional group elimination and formation of quinonic and hydroquinonic moieties. - Keywords: polyprenylbenzoquinol; polyprenylhydroquinone; allylcarbonate; ?-allyl palladium complex
- Bouzbouz, Samir,Kirschleger, Bernard,Villieras, Jean
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- Surface-mediated reactions. 5. Oxidation of sulfides, sulfoxides, and alkenes with tert-butyl hydroperoxide
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Silica gel mediates the reactivity of (CH3)3COOH, affording a convenient, environmentally benign method for oxidizing sulfides, sulfoxides, and alkenes. Electrophilic oxidation of sulfides and alkenes (Scheme 1A) and nucleophilic oxidation of sulfoxides (Scheme 1B) are apparently involved. Basic alumina mediates the oxidation of sulfoxides.
- Breton, Gary W.
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p. 3825 - 3828
(2007/10/02)
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- Synthesis of Vinyl Sulfide Analogs of 2,3-Oxidosqualene and Their Inhibition of 2,3-Oxidosqualene Lanosterol-Cyclases
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Syntheses of all trans(6E)-5-, (10E)-9-, (14E)-16- and (18E)-20-thia-2,3-oxidosqualenes as inhibitors of 2,3-oxidosqualene-lanosterol cyclase (OSC) are reported.To mimic the natural geometry of 2,3-oxidosqualene (2,3-OS), we required E-vinyl sulfides which were prepared by condensation of sulfur-substituted Wittig-Horner reagents (α-thioterpenoidyl diphenylphosphine oxides) with appropriate aldehydes.Mixtures of syn and anti α-hydroxydiphenylphosphine adducts were seperated by chromatography and the syn isomers were transformed to the E-vinyl sulfides.Both (6E)-5- and (18E)-20-thia-2,3-OS inhibited OSC from Candida albicans (IC50 = 47 and 0.2 μM, respectively) and rat liver (IC50 = 7.7 and 0.32 μM, respectively).Their activities were compared with those of previously synthesized (6E)-8- and (14E)-13-thia-2,3-Oss (IC50 = 0.68 and 45 μM, C. albicans, IC50 = 34 and 61 μM, rat liver, respectively).The best inhibitor among these compounds for the OSC of C. albicans and rat liver is the (18E)-20-thia-2,3-OS.This result suggests that modification of C-20 region of the 2,3-OS skeleton is an attractive strategy for development of OSC inhibitors.
- Zheng, Yi Feng,Dodd, Dharmpal S.,Oehlschlager, Allan C.,Hartman, Peter G.
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p. 5255 - 5276
(2007/10/02)
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- Stereoselective Synthesis of (+/-)-Irones
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β-, α-cis-, and α-trans-irones (1, 2a, and 2b) have been prepared via 2,5,6,6-tetramethyl-1-cyclohexene (7) and 1,4β,5,5-tetramethyl-6β-cyclohexene (8a) and its C-6 epimer (8b).Electrochemical epoxidation of
- Torii, Sigeru,Uneyama, Kenji,Matsunami, Setsuo
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