5309-56-8Relevant academic research and scientific papers
The Mechanism of Dehydrating Bimodules in trans-Acyltransferase Polyketide Biosynthesis: A Showcase Study on Hepatoprotective Hangtaimycin
Deng, Zixin,Dickschat, Jeroen S.,Dong, Yulu,Lu, Junlei,Luo, Minghe,Qi, Miaomiao,Shen, Kun,Sun, Guo,Sun, Yuhui,Tang, Lingjie,Xiang, Jin,Xu, Houchao,Yin, Zhiyong
supporting information, p. 19139 - 19143 (2021/08/03)
A bioassay-guided fractionation led to the isolation of hangtaimycin (HTM) from Streptomyces spectabilis CCTCC M2017417 and the discovery of its hepatoprotective properties. Structure elucidation by NMR suggested the need for a structural revision. A putative HTM degradation product was also isolated and its structure was confirmed by total synthesis. The biosynthetic gene cluster was identified and resembles a hybrid trans-AT PKS/NRPS biosynthetic machinery whose first PKS enzyme contains an internal dehydrating bimodule, which is usually found split in other trans-AT PKSs. The mechanisms of such dehydrating bimodules have often been proposed, but have never been deeply investigated. Here we present in vivo mutations and in vitro enzymatic experiments that give first and detailed mechanistic insights into catalysis by dehydrating bimodules.
Iron-Catalyzed Reactions of 2-Pyridone Derivatives: 1,6-Addition and Formal Ring Opening/Cross Coupling
Huang, Lin,Gu, Yiting,Fürstner, Alois
, p. 4017 - 4023 (2019/08/07)
In the presence of simple iron salts, 2-pyridone derivatives react with Grignard reagents under mild conditions to give the corresponding 1,6-addition products; if the reaction medium is supplemented with an aprotic dipolar cosolvent after the actual addition step, the intermediates primarily formed succumb to ring opening, giving rise to non-thermodynamic Z,E-configured dienoic acid amide derivatives which are difficult to make otherwise. Control experiments as well as the isolation and crystallographic characterization of a (tricarbonyl)iron pyridone complex suggest that the active iron catalyst generated in situ exhibits high affinity to the polarized diene system embedded into the heterocyclic ring system of the substrates, which likely serves as the actual recognition element.
Formal ring-opening/cross-coupling reactions of 2-pyrones: Iron-catalyzed entry into stereodefined dienyl carboxylates
Sun, Chang-Liang,Fuerstner, Alois
supporting information, p. 13071 - 13075 (2014/01/06)
Open access: Despite the exceptional level of sophistication in cross-coupling chemistry, reactions of substrates that incorporate the leaving group as an integral part into a heterocyclic scaffold are scarce. The title reaction outlines the utility of this reaction format (see scheme; acac=acetylacetonate), provides a convenient entry into stereodefined diene carboxylates, and adds a new chapter to the field of iron catalysis. Copyright
One-flask tethered ring closing metathesis-electrocyclic ring opening for the highly stereoselective synthesis of conjugated Z/E-dienes
Schmidt, Bernd,Kunz, Oliver
, p. 1008 - 1018 (2012/03/27)
A one-flask reaction sequence comprising ring closing metathesis (RCM) of butenoates derived from allylic alcohols and a base-mediated ring opening gives 2Z,4E-configured dienoic acids in high yields and stereoselectivities. Application of the method to the synthesis of the natural product fusanolide A suggests that the originally published structure was erroneously assigned and should be revised. Ring closing metathesis (RCM) of butenoates derived from allylic alcohols can be combined with base-induced ring opening in a one-flask sequence. In this way, dienoic acids become accessible in an operationally simple procedure in very high yields and excellent stereoselectivities, with the tether remaining in the product as a valuable functional group for further transformations. Copyright
Studies toward the synthesis of (-)-zampanolide: preparation of N-acyl hemiaminal model systems.
Troast, Dawn M,Porco Jr., John A
, p. 991 - 994 (2007/10/03)
[structure: see text] Synthesis of N-acyl hemiaminal model systems related to the side chain of the antitumor natural product zampanolide is reported. Key steps involve oxidative decarboxylation of N-acyl-alpha-amino acid intermediates, followed by ytterb
Total syntheses of (+)-zampanolide and (+)-dactylolide exploiting a unified strategy
Smith III, Amos B.,Safonov, Igor G.,Corbett, R. Michael
, p. 11102 - 11113 (2007/10/03)
The first total syntheses of (+)-zampanolide (1) and (+)-dactylolide (2), members of a new class of tumor cell growth inhibitory macrolides, have been achieved. Key features of the unified synthetic scheme included the stereocontrolled construction of the cis-2,6-disubstituted tetrahydropyran via a modified Petasis-Ferrier rearrangement, a highly convergent assembly of the macrocyclic domain, and, in the case of zampanolide, a Curtius rearrangement/acylation tactic to install the N-acyl hemiaminal. The complete relative and absolute stereochemistries for both (+)-zampanolide and (+)-dactylolide were also assigned, albeit tentatively in the case of (+)-zampanolide (1).
Stereochemistry of Thermolytic Base-catalysed Decarboxylation to form Cojugated Diene-Acids: Synthesis using Ethylidenemalonic Ester Condensation
Crombie, Leslie,Crombie, W. Mary L.
, p. 1267 - 1274 (2007/10/02)
The condensation of aromatic aldehydes with ethylidenemalonic ester in the presence of benzyltrimethylammonium hydroxide leads to 2(E),4(E)-half-esters, which are decarboxylated in refluxing pyridine to 2(E),4(E)-esters.When decarboxylated by thermolysis in quinoline at 130 deg C cinnamylidenemalonic acid gives almost pure 5-phenylpenta-2(Z),4(E)-dienoic acid which slowly stereomutates, but on continued heating at 170 deg C it passes over to give almost pure 2(E),4(E)-acid.In pyridine near its boiling point, however, the malonic acid is converted into a 64:36 mixture of 2(Z),4(E)-:2(E),4(E)-acids, the composition of which does not change on continued refluxing.The use of carboxy-labelled dideuteriomalonic acid in the pyridine reaction leads to 5-phenylpenta-2(Z),4(E)-dienoic acid and its 2(E),4(E)-stereoisomer, each having similar ca. 2.1 α/γ deuterium labelling.The latter stereoisomer does not arise by stereomutation, and a dual pathway originating from a common deuteriated lactone is proposed.Decarboxylation of the deuteriomalonic acid in quinoline at 130 deg C, giving almost pure 2(Z),4(E)-dienoic acid with ca. 2:1 α/γ labelling, involves only one of the pathways.The ethylidenemalonic acid method is suitable for the preparation of 2(E),4(E)-half-esters and 5-phenylpenta-2(Z),4(E)-dienoic acids having both electron-withdrawing as well as electron-releasing aryl substituents. 2(Z),4(E)-Sorbic acid can also be made from the corresponding malonic acid by quinoline-catalysed decarboxylation, whereas the classical pyridine-catalysed Doebner reaction forms almost entirely 2(E),4(E)-sorbic acid.
Synthesis of 2(E),4(E)-Dienamides and 2(E),4(E)-Dienoates from 1,3-Dienes via 2-Phenylsulfonyl 1,3-Dienes
Plobeck, Niklas A.,Baeckvall, Jan-E.
, p. 4508 - 4512 (2007/10/02)
A procedure for the preparation of 2E,4E unsaturated carboxylic acid derivatives from dienes was developed.Transformation of terminal 1,3-dienes to (E)-2-phenylsulfonyl 1,3-dienes and subsequent addition of a carboxy anion equivalent and elimination of benzenesulfinic acid led to 2,4-dienoic amides and esters.In this way the natural products N-isobutyl-2(E),4(E)-undecadienamide (1a), N-isobutyl-2(E),4(E)-decadienamide (pellitorine, 1b), and methyl 2(E),4(E)-decadienoate (1c) were obtained in high isomeric purity.
