- Enzymatic Addition of Alcohols to Terpenes by Squalene Hopene Cyclase Variants
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Squalene–hopene cyclases (SHCs) catalyze the polycyclization of squalene into a mixture of hopene and hopanol. Recently, amino-acid residues lining the catalytic cavity of the SHC from Alicyclobacillus acidocaldarius were replaced by small and large hydrophobic amino acids. The alteration of leucine 607 to phenylalanine resulted in increased enzymatic activity towards the formation of an intermolecular farnesyl–farnesyl ether product from farnesol. Furthermore, the addition of small-chain alcohols acting as nucleophiles led to the formation of non-natural ether-linked terpenoids and, thus, to significant alteration of the product pattern relative to that obtained with the wild type. It is proposed that the mutation of leucine at position 607 may facilitate premature quenching of the intermediate by small alcohol nucleophiles. This mutagenesis-based study opens the field for further intermolecular bond-forming reactions and the generation of non-natural products.
- Kühnel, Lisa C.,Nestl, Bettina M.,Hauer, Bernhard
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p. 2222 - 2225
(2017/10/09)
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- Synthesis and structure-activity relationships for cytotoxicity and apoptosis-inducing activity of (+)-halichonine B
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Halichonine B is a sesquiterpene alkaloid isolated from the marine sponge Halichondria okadai Kadota. Halichonine B has exhibited cytotoxicity against mammalian cancer cells and induced apoptosis in the human leukemia cell line HL60. Here we established a practical route for the synthesis of halichonine B and its analogues, and we evaluated their biological activities. It was revealed that the secondary amino groups in the side chain portion are important for the strong cytotoxicity of halichonine B and that the N11-prenyl group is unimportant. Halichonine B and its analogues were also observed to induce apoptosis in HL60 cells.
- Hayakawa, Ichiro,Nakamura, Tomomi,Ohno, Osamu,Suenaga, Kiyotake,Kigoshi, Hideo
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p. 9969 - 9976
(2015/10/12)
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- Total synthesis of bioactive drimane-epoxyquinol hybrid natural products: Macrophorin A, 4′-oxomacrophorin A, and 1′-epi-craterellin A
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Total synthesis of novel hybrid natural products, merosesquiterpenoids macrophorin A, 4′-oxomacrophorin A, and 1′-epi-craterellin A has been accomplished following a general strategy based on a sacrificial Diels-Alder-retroDiels-Alder approach to control regio- and stereoselectivity.
- Garai, Sumanta,Mehta, Goverdhan
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p. 6252 - 6256
(2014/12/10)
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- SESQUITERPENES FOR ANTIFUNGAL APPLICATIONS
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Bicyclic sesquiterpene compounds exhibiting antifungal characteristics are formulated into antifungal compositions for use in the treatment of fungal infections in humans, animals, and plants. Particularly, sesquiterpene alcohols derived from drimane have been discovered to possess broad-spectrum antifungal characteristics. Exemplary antifungal sesquiterpene compounds include albicanol and drimenol, which have been shown effective against a number of pathogenic fungi.
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Page/Page column 14
(2013/03/26)
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- New access to sesquiterpene hydroquinones: Synthesis of (+)-ent-chromazonarol
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A facile access to optically active (+)-ent-chromazonarol ent-1, isolated from the sponge Disidea pallescens, is reported from commercially available (+)-manool 4. Copyright Taylor & Francis LLC.
- Villamizar, Jose,Plata, Federico,Canudas, Nieves,Tropper, Eleonora,Fuentes, Juan,Orcajo, Angel
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p. 311 - 320
(2007/10/03)
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- Convenient synthesis of drimenol and its oxidation with selenium dioxide
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A convenient synthesis of drimenol by treatment of readily available drimane-8α, 11-diol 11-monoacetate with sulfuric acid in ethanol under mild conditions was developed. Oxidation of drimenol with selenium dioxide gives known drim-7-ene-9α, 11-diol and drim-7-ene-11,12-diol as the major products.
- Kuchkova,Aricu,Dragalin,Vlad
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p. 2862 - 2865
(2007/10/03)
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- Enzymatic cyclization reactions of geraniol, farnesol and geranylgeraniol, and those of truncated squalene analogs having C20 and C25 by recombinant squalene cyclase
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The substrate specificity of squalene-hopene cyclase was investigated using the C10-C25 analogs including naturally occurring substances, e.g. geraniol (C10), farnesol (C15) and geranylgeraniol (C20). No cyclization occurred for geraniol, but a significantly high conversion ratio (64%) was observed for farnesol, yielding the cyclic sesquiterpenes consisting of 6/6-fused bicyclic ring systems. Among them, an attractive compound having C30 was produced, in the structure of which acyclic the farnesol unit is linked to the bicyclic skeleton through ether linkage. Conversion of geranylgeraniol was low (ca. 12%). The squalene analogs having C20 and C25 also were cyclized in yields of ca. 33-36%, but the analogs having the methyl group at C(7) and/or at C(11) underwent no cyclization; the large steric bulk size of C(7)-Me and/or C(11)-Me, which is arranged in α-disposition for all the pre-chair conformation, would have interacted repulsively with the cyclase recognition site near to the C(7) and/or C(11), resulting in no construction of the all-chair conformation inside the reaction cavity. A relatively low yield of geranylgeraniol indicated that a less bulky hydrogen atom must be located at C(14) for the efficient polycyclization reaction. The squalene cyclase shows remarkably broad substrate specificity to accept the truncated analogs having carbon-chain lengths of C15-C25 in addition to C 30.
- Hoshino, Tsutomu,Kumai, Yuko,Kudo, Isao,Nakano, Shin-Ichi,Ohashi, Shumi
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p. 2650 - 2657
(2007/10/03)
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