469-61-4Relevant articles and documents
The Wender Cedrene Synthesis Revisited: A Catalytic Enantioselective Entry to the Chiral Key Intermediate
Westphal, Julia,Schumacher, Christian Eric,Schmalz, Hans-Günther
, (2017)
The seminal synthesis of the sesquiterpene (±)-α-cedrene reported by Wender in 1981 offers a uniquely short and elegant access to the bridged-tricyclic target compound by exploiting an intramolecular arene-olefin photocycloaddition. However, the synthesis was performed only in the racemic series so far. This synthesis was now re-investigated and the catalytic methods for the enantioselective preparation of the chiral key intermediate were evaluated. It was found that Cu-catalyzed allylic substitution of a cinnamyl chloride with MeMgBr in the presence of a Taddol-derived chiral phosphine-phosphite ligand affords the corresponding (1-methylallyl)arene with high enantioselectivity (94% ee). Hydroboration and subsequent Suzuki coupling gave (R)-curcuphenol methyl ether from which (-)-α-cedrene was prepared along the route paved by Wender.
Olefins by Transition Metal Catalyzed Elimination Reactions from Tertiary Alcohols and Acetates
Schmidt, Thomas
, p. 8155 - 8160 (1991)
The elemination reaction of water or acetic acid from tertiary alcohols and acetates is catalyzed by transition metal complexes.Olefins are obtained in high yields with catalyst dependent regioselectivity. β-Cedrene 6b can be prepared as major product from cedryl acetate 5.Key Words: Catalytic elimination; olefin formation; molybdenum catalysts; regioselectivity; α- and β-cedrene
Titanium and Cobalt Bimetallic Radical Redox Relay for the Isomerization of N -Bz Aziridines to Allylic Amides
Wood, Devin P.,Guan, Weiyang,Lin, Song
supporting information, p. 4213 - 4220 (2021/08/10)
Herein a bimetallic radical redox-relay strategy is employed to generate alkyl radicals under mild conditions with titanium(III) catalysis and terminated via hydrogen atom transfer with cobalt(II) catalysis to enact base-free isomerizations of N-Bz aziridines to N-Bz allylic amides. This reaction provides an alternative strategy for the synthesis of allylic amides from alkenes via a three-step sequence to accomplish a formal transpositional allylic amination.
Cedar camphor derivative as well as preparation method and application thereof
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Paragraph 0051-0054, (2021/04/03)
The invention relates to the technical field of synthetic drugs, in particular to a cedar camphor derivative as well as a preparation method and an application thereof. The cedar camphor derivative isany one of compounds shown in the following structural formula, tautomers, hydrates, solvates or pharmaceutically acceptable salts thereof, and the cedar camphor derivative has a good treatment effect on viruses, especially influenza viruses, so that the application range of the cedar camphor and the derivatives thereof is expanded, and the variety of the cedar camphor derivatives is expanded.
Sesquiterpene Cyclizations inside the Hexameric Resorcinarene Capsule: Total Synthesis of δ-Selinene and Mechanistic Studies
Zhang, Qi,Tiefenbacher, Konrad
supporting information, p. 12688 - 12695 (2019/08/12)
The synthesis of terpene natural products remains a challenging task due to the enormous structural diversity in this class of compounds. Synthetic catalysts are unable to reproduce the tail-to-head terpene cyclization of cyclase enzymes, which create this diversity from just a few simple linear terpene substrates. Recently, supramolecular structures have emerged as promising enzyme mimetics. In the present study, the hexameric resorcinarene capsule was utilized as an artificial cyclase to catalyze the cyclization of sesquiterpenes. With the cyclization reaction as the key step, the first total synthesis of the sesquiterpene natural product δ-selinene was achieved. This represents the first total synthesis of a sesquiterpene natural product that is based on the cyclization of a linear terpene precursor inside a supramolecular catalyst. To elucidate the reaction mechanism, detailed kinetic studies and kinetic isotope measurements were performed. Surprisingly, the obtained kinetic data indicated that a rate-limiting encapsulation step is operational in the cyclization of sesquiterpenes.
Stereoselective quenching of cedryl carbocation in epicedrol biosynthesis
Shinde, Sandip S.,Navale, Govinda R.,Said, Madhukar S.,Thulasiram, Hirekodathakallu V.
supporting information, p. 1161 - 1164 (2016/03/09)
Epicedrol synthase catalyzes the cyclization of achiral diphosphate substrate, (E,E)-farnesyldiphosphate (FPP) into epicedrol. GC-MS analysis of assay extracts obtained by incubating FPP with epicedrol synthase in 21.6 at % H218O buffer showed the molecular ion of 224 for epicedrol. The labeled oxygen study presented here unambiguously demonstrates that the hydroxyl group of the epicedrol synthase enzymatic product, epicedrol, is derived from a water molecule, not from the phosphate moiety of the FPP.
An oxidative dearomatization-induced [5 + 2] cascade enabling the syntheses of α-cedrene, α-pipitzol, and sec -cedrenol
Green, Jason C.,Pettus, Thomas R. R.
, p. 1603 - 1608 (2011/04/16)
Efficient syntheses of α-cedrene (1), α-pipitzol (2), and sec-cedrenol (3) were carried out using a new method, which was inspired by the proposed biosynthesis of the tricyclic skeleton of cedrol (12). The key transformation begins with the oxidative dearomatization of curcuphenol (5a) followed by an intramolecular [5 + 2] cycloaddition of the respective phenoxonium intermediate across the tethered olefin. The benzylic stereocenter effectively guides the formation of the first two stereocenters during the [5 + 2] reaction. The cascade then terminates with the selective incorporation of acetic acid to generate a third stereocenter, setting it apart from other previous cationic [5 + 2] reactions. The phenolic precursors (5a-h) are constructed from readily available salicylaldehydes, either as the racemate (one pot) or as a specific enantiomer (four pots) by a modification to our method for the generation of ortho-quinone methides (o-QMs).
Structural elucidation of cisoid and transoid cyclization pathways of a sesquiterpene synthase using 2-fluorofarnesyl diphosphates
Noel, Joseph P.,Dellas, Nikki,Faraldos, Juan A.,Zhao, Marylin,Hess, B. Andes,Smentek, Lidia,Coates, Robert M.,O'Maille, Paul E.
body text, p. 377 - 392 (2011/02/23)
Sesquiterpene skeletal complexity in nature originates from the enzyme-catalyzed ionization of (trans,trans)-farnesyl diphosphate (FPP) (1a) and subsequent cyclization along either 2,3-transoid or 2,3-cisoid farnesyl cation pathways. Tobacco 5-epi-aristolochene synthase (TEAS), a transoid synthase, produces cisoid products as a component of its minor product spectrum. To investigate the cryptic cisoid cyclization pathway in TEAS, we employed (cis,trans)-FPP (1b) as an alternative substrate. Strikingly, TEAS was catalytically robust in the enzymatic conversion of (cis,trans)-FPP (1b) to exclusively (?99.5%) cisoid products. Further, crystallographic characterization of wild-type TEAS and a catalytically promiscuous mutant (M4 TEAS) with 2-fluoro analogues of both all-trans FPP (1a) and (cis,trans)-FPP (1b) revealed binding modes consistent with preorganization of the farnesyl chain. These results provide a structural glimpse into both cisoid and transoid cyclization pathways efficiently templated by a single enzyme active site, consistent with the recently elucidated stereochemistry of the cisoid products. Further, computational studies using density functional theory calculations reveal concerted, highly asynchronous cyclization pathways leading to the major cisoid cyclization products. The implications of these discoveries for expanded sesquiterpene diversity in nature are discussed.
Bisabolyl-derived sesquiterpenes from tobacco 5-epi-aristolochene synthase-catalyzed cyclization of (2Z,6E)-farnesvl diohosohate
Faraldos, Juan A.,O'Maille, Paul E.,Dellas, Nikki,Noel, Joseph P.,Coates, Robert M.
experimental part, p. 4281 - 4289 (2010/05/15)
We report the structures and stereochemistry of seven bisabolyl-derived sesquiterpenes arising from an unprecedented 1,6-cyclization (cisoid pathway) efficiently catalyzed by tobacco 5-epi-aristolochene synthase (TEAS). The use of (2Z,6E)-farnesyl diphosphate as an alternate substrate for recombinant TEAS resulted in a robust enzymatic cyclization to an array of products derived exclusively (≥99.5%) from the cisoid pathway, whereas these same products account for ca. 2.5% of the total hydrocarbons obtained using (2E,6E)-farnesyl diphosphate. Chromatographic fractionations of extracts from preparative incubations with the 2Z,6E substrate afforded, in addition to the acyclic allylic alcohols (2Z,6E)-farnesol (6.7%) and nerolidol (3.6%), five cyclic sesquiterpene hydrocarbons and two cyclic sesquiterpene alcohols: (+)-2-epiprezizaene (44%), (-)-α-cedrene (21.5%), (R)-(-)-β-curcumene (15.5%), R-acoradiene (3.9%), 4-epi-α-acoradiene (1.3%), and equal amounts of α-bisabolol (1.8%) and epi-R-bisalolol (1.8%). The structures, stereochemistry, and enantiopurities were established by comprehensive spectroscopic analyses, optical rotations, chemical correlations with known sesquiterpenes, comparisons with literature data, and GC analyses. The major product, (+)-2-epi-prezizaene, is structurally related to the naturally occurring tricyclic alcohol, jinkohol (2-epi-prezizaan-7 β-ol). Cisoid cyclization pathways are proposed by which all five sesquiterpene hydrocarbons are derived from a common (7R)-β-bisabolyl+/pyrophosphate - ion pair intermediate. The implications of the cisoid catalytic activity of TEAS are discussed.
Total synthesis of α-cedrene: A new strategy utilizing N- aziridinylimine radical chemistry
Lee, Hee-Yoon,Lee, Sejin,Kim, Deogil,Kim, Byung Kyu,Bahn, Jong Soo,Kim, Sunggak
, p. 7713 - 7716 (2007/10/03)
Tandem free radical cycloaddition reaction of the N-Aziridinylimine intermediate produced tricyclo[5.3.1.01,5]undecane skeleton stereoselectively. A total synthesis of α-cedrene was completed in three step sequence from the cyclization product.
