111-02-4Relevant academic research and scientific papers
Mutated variants of squalene-hopene cyclase: Enzymatic syntheses of triterpenes bearing oxygen-bridged monocycles and a new 6,6,6,6,6-fusded pentacyclic scaffold, named neogammacerane, from 2,3-oxidosqualene
Fukuda, Yoriyuki,Watanabe, Takashi,Hoshino, Tsutomu
, p. 6987 - 7000 (2018)
Squalene-hopene cyclase (SHC) catalyzes the conversion of acyclic squalene molecule into a 6,6,6,6,5-fused pentacyclic hopene and hopanol. SHC is also able to convert (3S)-2,3-oxidosqualene into 3β-hydroxyhopene and 3β-hydroxyhopanol and can generate 3α-hydroxyhopene and 3α-hydroxyhopanol from (3R)-2,3-oxidosqualene. Functional analyses of active site residues toward the squalene cyclization reaction have been extensively reported, but investigations of the cyclization reactions of (3R,S)-oxidosqualene by SHC have rarely been reported. The cyclization reactions of oxidosqualene with W169X, G600F/F601G and F601G/P602F were examined. The variants of the W169L generated new triterpene skeletons possessing a 7-oxabicyclo[2.2.1]heptane moiety (oxygen-bridged monocycle) with (1S,2S,4R)- and (1R,2S,4S)-stereochemistry, which were produced from (3R)- and (3S)-oxidosqualenes, respectively. The F601G/P602F double mutant also furnished a novel triterpene, named neogammacer-21(22)-en-3β-ol, consisting of a 6,6,6,6,6-fused pentacyclic system, in which Me-29 at C-22 of the gammacerane skeleton migrated to C-21. We propose to name this novel scaffold neogammacerane. The formation mechanisms of the enzymatic products from 2,3-oxidosqualene are discussed.
Cloning, expression analysis and functional characterization of squalene synthase (SQS) from tripterygium wilfordii
Zhang, Bin,Liu, Yan,Chen, Mengmeng,Feng, Juntao,Ma, Zhiqing,Zhang, Xing,Zhu, Chuanshu
, (2018)
Celastrol is an active triterpenoid compound derived from Tripterygium wilfordii which is well-known as a traditional Chinese medicinal plant. Squalene synthase has a vital role in condensing two molecules of farnesyl diphosphate to form squalene, a key precursor of triterpenoid biosynthesis. In the present study, T. wilfordii squalene synthase (TwSQS) was cloned followed by prokaryotic expression and functional verification. The open reading frame cDNA of TwSQS was 1242 bp encoding 413 amino acids. Bioinformatic and phylogenetic analysis showed that TwSQS had high homology with other plant SQSs. To obtain soluble protein, the truncated TwSQS without the last 28 amino acids of the carboxy terminus was inductively expressed in Escherichia coli Transetta (DE3). The purified protein was detected by SDS-PAGE and Western blot analysis. Squalene was detected in the product of in vitro reactions by gas chromatograph-mass spectrometry, which meant that TwSQS did have catalytic activity. Organ-specific and inducible expression levels of TwSQS were detected by quantitative real-time PCR. The results indicated that TwSQS was highly expressed in roots, followed by the stems and leaves, and was significantly up-regulated upon MeJA treatment. The identification of TwSQS is important for further studies of celastrol biosynthesis in T. wilfordii.
Enzymic products of the 2,3-oxidosqualene analog having an ethyl residue at 10-position. First trapping of the trimethylcyclohexanone ring by lanosterol synthase
Hoshino, Tsutomu,Sakai, Yoshiyuki
, p. 7319 - 7323 (2001)
Incubation of squalene analog, (3RS)-(6E,10E,14E,18E)-10-ethyl-2,6,19,23-tetramethyl-2,3-epoxytetracosa-6, 10,14,18,22-pentaene with 2,3-oxidosqualene-lanosterol cyclase from pig liver gave four products, consisting of two mono-, one tri- and one tetracyc
Squalene Synthetase. Inhibition by Ammonium Analogues of Carbocationic Intermediates in the Conversion of Presqualene Diphosphate to Squalene
Poulter, C. Dale,Capson, Todd L.,Thompson, Michael D.,Bard, Ronda S.
, p. 3734 - 3739 (1989)
Squalene synthetase (EC 2.5.1.21) catalyzes the formation of squalene (3) from farnesyl diphosphate (1) via presqualene diphosphate (2) in two steps.The mechanism of the rearrangement of 2 to 3 was studied with stable ammonium analogues 6 and 7 of primary and tertiary cyclopropylcarbinyl cations 4 and 5, respectively, proposed as intermediates.In non-pyrophosphate-containing buffers, 6 and 7 were not inhibitors.However, the combination of 6 or 7 with PPi produced potent synergistic inhibition of squalene synthesis from 1 and 2.Amino acid 8, an analogue in whicha phosphonophosphate moiety was tethered to the amino group in 6, was a potent inhibitor of squalene synthesis in pyrophosphate-free buffers.When synthesis of 2 and 3 from 1 was measured simultaneously in the presence of 8, both rates were depressed in an identical manner.It was concluded that squalene synthetase has a single active site which catalyzes 1 --> 2 and 2 --> 3.The mechanism of the second reaction is discussed.
ent-Kaurene and squalene synthesis in Fusarium fujikuroi cell-free extracts
Fernandez-Martin, Rafael,Domenech, Carlos,Cerda-Olmedo, Enrique,Avalos, Javier
, p. 723 - 728 (2000)
Sterols and gibberellins are the main terpenoids in the Ascomycete Fusarium fujikuroi. Their respective precursors squalene and ent-kaur-16-ene (henceforth called kaurene) were the main terpenoids synthesised from radioactive mevalonate by extracts of F. fujikuroi in vitro. Kaurene predominated when the extracts were obtained from mycelia engaged in gibberellin production. Squalene predominated in all other cases, and particularly when the extracts were obtained from mutants with various defects in gibberellin synthesis or nitrogen-fed wild-type cultures. New protein synthesis was required to maintain the production of gibberellins in vivo and of kaurene in vitro, but not to maintain the capacity to produce squalene in vitro. Addition of a nitrogen source to cultures engaged in gibberellin production caused a large, transient increase in the mycelial concentration of L-glutamine and abolished the accumulation of gibberellins immediately and the capacity to produce kaurene later. (C) 2000 Elsevier Science Ltd.
Reductive coupling of terpenic allylic halides catalyzed by Cp 2TiCl: A short and efficient asymmetric synthesis of onocerane triterpenes
Barrero, Alejandro F.,Herrador, M. Mar,Del Moral, Jose F. Quilez,Arteaga, Pilar,Arteaga, Jesus F.,Piedra, Maria,Sanchez, Elena M.
, p. 2301 - 2304 (2005)
(Chemical Equation Presented) Titanocene chloride catalyzes the regioselective α,α′-homocoupling of terpenic allylic halides. This process has been employed in the short and effective synthesis of terpenoids such as β-onoceradiene (1), β-onocerin (2), and squalene (3). Evidence is presented for η1-allyltitanium species being involved in the coupling.
PALLADIUM-CATALYZED COUPLING OF ALLYLIC ACETATES WITH ZINC
Sasaoka, Shin-ichi,Yamamoto, Taku,Kinoshita, Hideki,Inomata, Katsuhiko,Kotake, Hiroshi
, p. 315 - 318 (1985)
Allylic acetates were coupled with zinc dust in the presence of a catalytic amount of to give the corresponding 1,5-dienes under mild conditions in high yields.Significant cosolvent effects were found with methanol or 1,2-ethanediol in tetrahydrofuran.
Hexacarbonylmolybdenum(0)-Catalyzed Reductive Coupling of Allylic Acetates
Masuyama, Yoshiro,Otake, Kiyotaka,Kurusu, Yasuhiko
, p. 1527 - 1528 (1987)
The reaction of allylic acetates with zinc in the presence of a catalytic amount of hexacarbonylmolybdenum(0) led to reductive coupling for the formation of a 1,5-diene framework.Reductive coupling of nerolidyl acetate provided squalene and its isomers in high yield.
SYNTHESIS OF E,E-FARNESOL, FARNESYL ACETATE AND SQUALENE FROM FARNESENE VIA FARNESYL CHLORIDE
-
, (2019/12/28)
The present disclosure provides methods for preparing polyunsaturated hydrocarbons, such as E,E-farnesol, farnesyl acetate and squalene, by base catalyzed addition of a dialkylamine to a 3-methylene-1-alkene, such as farnesene. The present disclosure also provides compositions including one more farnesene derivatives prepared using the disclosed methods.
Homocoupling versus reduction of radicals: An experimental and theoretical study of Ti(iii)-mediated deoxygenation of activated alcohols
Prieto, Consuelo,González Delgado, José A.,Arteaga, Jesús F.,Jaraíz, Martín,López-Pérez, José L.,Barrero, Alejandro F.
, p. 3462 - 3469 (2015/03/18)
A detailed experimental and theoretical study corroborates that the reductive deoxygenation of activated (allylic or benzylic) alcohols with excess Ti(iii) proceeds via an allyl(benzyl)-radical and allyl(benzyl)-Ti, which is protonated, regioselectively in the case of allylic derivatives. The H atom of the newly formed C-H bond in the product originates from the -OH group of the starting material. The deoxygenation of lithium alkoxides or alcohols by using 1.0 mol of Ti(iii) leads to the corresponding dimerization products in good yields. An excellent agreement with the experimental data was obtained by using a reaction kinetics simulator to discriminate between competing reactions.
