468-68-8Relevant academic research and scientific papers
Practical isolation of polygodial from Tasmannia lanceolata: A viable scaffold for synthesis
Just, Jeremy,Jordan, Timothy B.,Paull, Brett,Bissember, Alex C.,Smith, Jason A.
, p. 11200 - 11207 (2015)
Polygodial, a valuable sesquiterpene dialdehyde featuring an epimerizable stereocenter was efficiently extracted and isolated in gram-scale quantities (3.3% w/w) from Tasmannia lanceolata (Tasmanian native pepper) via a recently developed rapid pressurised hot water extraction (PHWE) technique that utilises an unmodified household espresso machine. This method was compared to the maceration of T. lanceolata under a range of conditions. Polygodial was used to achieve semi-syntheses of closely related sesquiterpene natural products drimendiol, (-)-drimenol, (+)-euryfuran, and some non-natural derivatives.
TERPENOIC ACID GLYCERIDES FROM THE DORID NUDIBRANCH ARCHIDORIS MONTEREYENSIS
Gustafson, Kirk,Andersen, Raymond J.,Chen, Marie H.M.,Clardy, Jon,Hochlowski, Jill E.
, p. 11 - 14 (1984)
Extracts of the dorid nudibranch Archidoris montereyensis contain a diterpenoic acid glyceride 1 whose structure has been determined by x-ray diffraction analysis.The structure of a minor metabolite, the sesquiterpenoic acid glyceride 2, was determined by chemical correlation.
Elimination of C-8-functional groups from driman-8α,11-diol-11- monoacetate and-diacetate
Kuchkova,Aryku,Barba,Vlad
, p. 412 - 416 (2007)
The dehydration products of driman-8α,11-diol-11-monoacetate that are formed upon reaction with several dehydrating agents and the products from elimination of the C-8 acetoxy group in driman-8α,11-diol diacetate were investigated in detail. A new effective synthesis of drimenylacetate from driman-8α, 11-diol-11-monoacetate by its regioselective dehydration using methanesulfonic acid trimethylsilyl ether was developed.
Synthesis of 11-aminodrim-7-ene from drimenol
Kuchkova,Arycu,Vlad
, p. 367 - 370 (2009)
11-Aminodrim-7-ene was synthesized from drimenol in four steps. Drimenol was oxidized into drimenal and its oxime was dehydrated by p-tosylchloride or acetic anhydride in pyridine to form 9-cyano-11-nordrim-7-ene, reduction of which by LiAlH4 in the presence of anhydrous AlCl3 produced 11-aminodrim-7-ene. The reaction of 9-cyano-11-nordrim-7-ene, NaBH 4, and CoCl2?6H2O produced a mixture of drimenylamine and 7,8-dihydrodrimenylamine in a 2:1 ratio.
Synthesis and bio-inspired optimization of drimenal: Discovery of chiral drimane fused oxazinones as promising antifungal and antibacterial candidates
Li, Dangdang,Zhang, Shasha,Song, Zehua,Li, Wei,Zhu, Feng,Zhang, Jiwen,Li, Shengkun
supporting information, p. 558 - 567 (2017/12/07)
The synthesis of antifungal natural product drimenal was accomplished. Bio-inspired optimization protruded chiral 8-(R)-drimane fused oxazinone D as a lead, considering favorable physicochemical profiles for novel pesticides. The improved scalable synthesis of scaffold D was implemented by Hofmann rearrangment under mild conditions. Detailed structural optimization was discussed for both antifungal and antibacterial exploration. Substituted groups (SGs) with C3～C5 hydrocarbon chain are recommended for exploration of antifungal agents, while substituents with C4～C6 carbon length are preferred for antibacterial ingredients. The chiral drimane fused oxazinone D8 was selected as a promising antifungal candidate against Botrytis cirerea, with an EC50 value of 1.18 mg/L, with the enhancement of up to >25 folds and >80 folds than the mother compound D, and acyclic counterpart AB5, respectively. The in vivo bioassay confirmed much better preservative effect of D8 than that of Carbendazim. The chiral oxazinone variant D10 possessed prominent antibacterial activity, with MIC values of 8 mg/L against both Bacillus subtilis and Ralstonia solanacearum, showing advantages over the positive control streptomycin sulfate.
Enzymatic Addition of Alcohols to Terpenes by Squalene Hopene Cyclase Variants
Kühnel, Lisa C.,Nestl, Bettina M.,Hauer, Bernhard
, p. 2222 - 2225 (2017/10/09)
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.
Synthesis and structure-activity relationships for cytotoxicity and apoptosis-inducing activity of (+)-halichonine B
Hayakawa, Ichiro,Nakamura, Tomomi,Ohno, Osamu,Suenaga, Kiyotake,Kigoshi, Hideo
, p. 9969 - 9976 (2015/10/12)
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.
SHIP1 MODULATORS AND METHODS RELATED THERETO
-
, (2014/07/23)
Compounds of formula (I): [Formula should be inserted here]; where [Formula should be inserted here], n, R1, R4a, R4b, R5, R7 and R8 are defined herein, or pharmaceutically acceptable salts thereof, are described herein. The disclosed compounds have activity as SHIP1 modulators, and thus may be used to treat any of a variety of diseases, disorders or conditions that would benefit from SHIP1 modulation. Compositions comprising a compound of formula (I) in combination with a pharmaceutically acceptable carrier or diluent are also disclosed, as are methods of SHIP1 modulation by administration of such compounds to an animal in need thereof.
Biogenetically inspired total synthesis of (+)-liphagal: A potent and selective phosphoinositide 3-kinase α (PI3Kα) inhibitor from the marine sponge Aka coralliphaga
Kamishima, Takaaki,Kikuchi, Takuya,Narita, Koichi,Katoh, Tadashi
, p. 3443 - 3450 (2014/06/09)
A biologically attractive and structurally unique marine natural product, (+)-liphagal, was biomimetically synthesized in 29% overall yield in a longest linear sequence of 13 steps from commercially available (+)-sclareolide. This synthesis involved the following crucial steps: (i) stereocontrolled hydrogenation of an endo-olefinic decalin to install the C8 stereogenic centre present in the requisite decalin segment; (ii) coupling of the decalin segment with an aromatic moiety to assemble the desired carbon skeleton; (iii) ring expansion of a proposed biogenetic intermediate followed by benzofuran formation to establish the requisite tetracyclic core structure. A few new aspects of the proposed biosynthetic pathway to this class of natural products were revealed. Copyright
Molecular cloning and characterization of drimenol synthase from valerian plant (Valeriana officinalis)
Kwon, Moonhyuk,Cochrane, Stephen A.,Vederas, John C.,Ro, Dae-Kyun
, p. 4597 - 4603 (2015/02/19)
Drimenol, a sesquiterpene alcohol, and its derivatives display diverse bio-activities in nature. However, a drimenol synthase gene has yet to be identified. We identified a new sesquiterpene synthase cDNA (VoTPS3) in valerian plant (Valeriana officinalis). Purification and NMR analyses of the VoTPS3-produced terpene, and characterization of the VoTPS3 enzyme confirmed that VoTPS3 synthesizes (-)-drimenol. In feeding assays, possible reaction intermediates, farnesol and drimenyl diphosphate, could not be converted to drimenol, suggesting that the intermediate remains tightly bound to VoTPS3 during catalysis. A mechanistic consideration of (-)-drimenol synthesis suggests that drimenol synthase is likely to use a protonation-initiated cyclization, which is rare for sesquiterpene synthases. VoTPS3 can be used to produce (-)-drimenol, from which useful drimane-type terpenes can be synthesized.
