Total Syntheses of the Tetracyclic Cyclopiane Diterpenes Conidiogenone, Conidiogenol, and Conidiogenone B

Hou, Si‐Hua; Tu, Yong‐Qiang; Wang, Shuanghu; Xi, Chao-Chao; Zhang, Fu‐Min; Wang, Shaohua; Li, Yantao; Liu, Lin

doi:10.1002/anie.201600529

Cited by 62 publications

(42 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For compound 4 , the crystalline sponge method was applied, an X‐ray‐based technique that allows structural data to be determined from small quantities of material . The absolute configuration of its derivative 5 was based on an enantioselective total synthesis, whereas for 6 and 9 – 11 obtained from Fusarium enzymes, calculated and experimental electronic circular dichroism (ECD) spectra were compared. Compound 3 from Fusarium was shown to have the same absolute configuration as 3 from E. variecolor based on a comparison of their optical rotations.…”

Section: Methodsmentioning

confidence: 99%

A Family of Related Fungal and Bacterial Di‐ and Sesterterpenes: Studies on Fusaterpenol and Variediene

et al. 2019

View full text Add to dashboard Cite

The absolute configuration of fusaterpenol (GJ1012E) has been revised by an enantioselective deuteration strategy. A bifunctional enzyme with a terpene synthase and a prenyltransferase domain from Aspergillus brasiliensis was characterised as variediene synthase, and the absolute configuration of its product was elucidated. The uniform absolute configurations of these and structurally related di‐ and sesterterpenes together with a common stereochemical course for the geminal methyl groups of GGPP unravel a similar conformational fold of the substrate in the active sites of the terpene synthases. For variediene, a thermal reaction observed during GC/MS analysis was studied in detail for which a surprising mechanism was uncovered.

show abstract

Section: Methodsmentioning

confidence: 99%

A Family of Related Fungal and Bacterial Di‐ and Sesterterpenes: Studies on Fusaterpenol and Variediene

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Total syntheses of various triquinanes were executed through TMM diyl [3+2] cycloaddition reaction, and complex natural products with multiple quaternary centers were successfully synthesized through the TMM diyl‐mediated tandem cycloaddition reaction. Following these successful examples, we were to extend the synthetic strategy to the total synthesis of another challenging structure of tetracyclic diterpene, conidiogenone B, though total synthesis of conidiogenone B did not appear straightforward through the tandem cycloaddition reaction via TMM diyl [3+2] cycloaddition reaction …”

Section: Introductionmentioning

confidence: 99%

“…It was anticipated that a known synthetic intermediate ( 7 ) of conidiogenone B ( 8 ) could be prepared from 6 by introducing the gem ‐dimethyl quaternary center. The tetracyclic compound 6 was expected to be obtained from 5 through the TMM diyl‐mediated tandem cycloaddition reaction (Figure ).…”

Section: Introductionmentioning

confidence: 99%

Unexpected Selectivity of Intramolecular [3+2] Cycloaddition of Trimethylenemethane (TMM) Diyl toward Total Synthesis of Conidiogenone B

et al. 2020

View full text Add to dashboard Cite

In the course of a study toward a total synthesis of conidiogenone B through TMM diyl-mediated tandem cycloaddition reaction, unexpected regioselectivity for a bridged isomer was observed. The synthetic and computational studies [a] The synthesis commenced with chemoselective protection of commercially available Wieland-Miescher ketone 1 following the known procedure [9] (Scheme 1). Nucleophilic epoxidation of the resulting enone 9 afforded 10, and subsequent Eschenmoser-Tanabe fragmentation resulted in γ-ethynyl ketone 11. Introduction of an exo-cyclic methylene to the ketone moiety by Wittig reaction cleanly produced 3 in 78 %. Gratifyingly, 3 was successfully coupled with 4 generated from 12 in situ in the presence of CuI and LiOtBu in 1,4-dioxane, [10] to yield allene Full Paper Figure 2. Retrosynthetic analysis of conidiogenone B. 13 in 81 %. Deprotection of the dithiane moiety quantitatively afforded the ketone 14 that possessed all the carbon units for the tetracyclic structure of conidiogenone B. Scheme 1. Preparation of cycloaddition precursor 14.When the sodium salt of hydrazone compound 5 was heated to NaH, formation of 6 was expected through TMM diyl 17 via 15 and 16 (Scheme 2). While the intramolecular [3+2] cycloaddition reaction between the TMM diyl and olefin of 17 proceeded smoothly, to our surprise, the bridged product 18 was obtained as the major product which structure was unambiguously confirmed by single-crystal X-ray analysis. [11] In addition to the major product 18, 1,4-hydrogen atom transfer (1,4-HAT) product [12] 19 was obtained as a single diastereomer though the relative stereochemistry was not determined.Both of the products should have formed via radical intermediate 3 B obtained through the triplet pathway and the formation of the bridged isomer could be understood by the conformational analysis of the five-membered ring formation through Eur.

show abstract

“…Unfortunately,attempts to synthesize (À)-9 with high optical purity from 12 by the method described by Chen and Ghosez [10c] led to the product with only À60 % ee.T herefore, we resorted to the chiral resolution of rac-9.For this purpose, the stereoselective reduction of rac-9 with L-selectride afforded the alcohol rac-13 as as ingle diastereoisomer, which was converted into am ixture of the diastereomeric esters 14 and 15 with (1S,4R)-camphanoyl chloride.T he diastereoisomers 14 and 15 were separated chromatographically,h ydrolyzed, and oxidized with IBX to give (+ +)-and (À)-9 with an optical purity of 99 % ee.T he absolute configuration of 14 was confirmed by X-ray crystallographic analysis. [11] Subsequently,lithium-halogen exchange of 8 with t-BuLi gave the corresponding organolithium reagent, which was treated with ketone (À)-9 to give the product 16 as as ingle diastereoisomer after quenching with aqueous HCl solution. Protection of the tertiary alcohol group afforded the rearrangement precursor 7 in 92 %y ield.…”

mentioning

confidence: 99%

“…Thes tructure of 17 was confirmed by X-ray crystallographic analysis. [11] To ensure that the migration of the secondary rather than the tertiary carbon atom in precursor 7 dominated, and hence the desired regioselectivity,weintroduced aphenylthio group at the methylene carbon atom of 7 to enhance its electron density and increase its migratory aptitude. [12] Thus,(À)-9 was treated with freshly prepared LDAa nd then PhSSPh to provide the thioether product 9a in 68 %y ield (Scheme 3).…”

mentioning

confidence: 99%