Synthesis of the Core Structure of Daphnimacropodines

Chen, Yuye; Hu, Jingping; Guo, Lian‐Dong; Tian, Peilin; Xu, Tianyue; Xu, Jing

doi:10.1021/acs.orglett.9b01486

Cited by 15 publications

(10 citation statements)

References 83 publications

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“…Our synthetic exploration of this type of alkaloid, such as daphnimacropodine B, , started from bicyclic diketone compound 47 , which was bis-oxygenated to afford monomasked diol 48 (Scheme ). A hydroxyl-guided Simmons–Smith cyclopropanation diastereoselectively elaborated compound 49 .…”

Section: Synthetic Study Toward Daphnimacropodinesmentioning

confidence: 99%

“…Upon treatment with sodium hydride, carbamate 51 underwent an intramolecular aza-Michael addition that smoothly produced cyclic carbamate compound 52 . Subsequent construction of the hydropyrrole moiety was unexpectedly difficult . After many trials, a Au(I)-catalyzed alkyne hydration followed by an intramolecular aldol condensation afforded the desired hydropyrrole moiety in compound 54 , which possesses most of the key structural features of the daphniglaucin C-type alkaloids.…”

Section: Synthetic Study Toward Daphnimacropodinesmentioning

confidence: 99%

“…In addition to the four successful examples presented above, we would also like to briefly introduce our recent efforts 22 toward the synthesis of daphniglaucin C-type alkaloids 42 (Figure 6). Containing "only" a tetracyclic core system, these intriguing alkaloids are evidently as synthetically challenging as many other subfamily members of Daphniphyllum alkaloids, owing to their common structural features including a congested caged ring skeleton, vicinal quaternary centers, Our synthetic exploration of this type of alkaloid, such as daphnimacropodine B, 22,42b started from bicyclic diketone compound 47, which was bis-oxygenated to afford monomasked diol 48 (Scheme 6).…”

Section: Daphnimacropodinesmentioning

confidence: 99%

“…General strategies, such as rapid ring skeleton construction and highly selective reactions, are incorporated into our synthetic design . Starting from simple chiral bicyclic synthons, four complex Daphniphyllum alkaloids have been synthesized, while the synthesis of daphniglaucin C-type alkaloids has also been investigated . Here, we present a full account of these endeavors, comprising a difficult but exciting journey that has revealed many interesting synthetic strategies and methods and provided valuable insight into Daphniphyllum alkaloid synthesis.…”

Section: Introductionmentioning

confidence: 99%

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Total Synthesis of Daphniphyllum Alkaloids: From Bicycles to Diversified Caged Structures

Guo

Chen

2020

Acc. Chem. Res.

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Metrics & MoreArticle Recommendations CONSPECTUS: Native to the Asia-Pacific region and widely applied in traditional Chinese medicine, the genus Daphniphyllum has produced over 330 known Daphniphyllum alkaloids.Investigations into these alkaloids have shown an exceptional range of interesting bioactivities.Challenging and caged polycyclic architectures and the promising biological profiles make Daphniphyllum alkaloids intriguing synthetic targets. Based on their backbones, these alkaloids can be categorized into 13−35 structurally distinct subfamilies. In addition to our work, almost 30 impressive total syntheses of Daphniphyllum alkaloids from seven subfamilies, namely, daphniphylline-type, secodaphniphylline-type, daphnilactone A-type, bukittinggine-type, daphmanidin A-type, calyciphylline A-type, and calyciphylline B-type alkaloids, have been reported by 11 research groups. However, many Daphniphyllum alkaloid subfamilies remain inaccessible by chemical synthesis.In this Account, we summarize our recent endeavors in the total synthesis of Daphniphyllum alkaloids commencing from simple chiral bicyclic synthons. Daphniphyllum alkaloids with diversified skeletons from four different subfamilies, namely, calyciphylline A-type, daphnezomine A-type, bukittinggine-type, and yuzurimine-type alkaloids, have been achieved. Furthermore, the tricyclic core structure of daphniglaucin C-type alkaloids daphnimacropodines was also synthesized. First, we describe a 14-step synthesis of calyciphylline A-type alkaloid (−)-himalensine A, which features a mild Cu-mediated nitrile hydration, an intramolecular Heck reaction to assemble the pivotal 2-azabicyclo[3.3.1]nonane moiety, and a Meinwald rearrangement to introduce the critical oxidative state into the skeleton. We then introduce the synthesis of daphnezomine A-type alkaloid dapholdhamine B, which possesses a unique aza-adamantane core. This target molecule was fabricated using key reactions including Huang's amideactivation−annulation. An unexpected radical detosylation during the synthesis of dapholdhamine B further inspired an ambitious radical cyclization cascade strategy, which eventually led to an efficient total synthesis of bukittinggine-type alkaloid (−)-caldaphnidine O. This highly chemo-, regio-, and stereoselective radical reaction cascade also shed light on the synthetic strategy of other alkaloids with caged structures. We next describe the first total synthesis of yuzurimine-type alkaloid (+)-caldaphnidine J. The key steps in our approach include a Pd-catalyzed regioselective hydroformylation and a novel Swern oxidation/ketene dithioacetal Prins reaction cascade. The work has achieved the first synthesis of a member of the largest subfamily of Daphniphyllum alkaloids. Finally, we show our efforts toward the total synthesis of daphniglaucin C-type alkaloids. Overall, we hope that the interesting strategies and synthetic methods demonstrated in our efforts could inspire a wide variety of additional applications to natural product synthesis.

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Section: Synthetic Study Toward Daphnimacropodinesmentioning

confidence: 99%

Section: Synthetic Study Toward Daphnimacropodinesmentioning

confidence: 99%

Section: Daphnimacropodinesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Total Synthesis of Daphniphyllum Alkaloids: From Bicycles to Diversified Caged Structures

Guo

Chen

2020

Acc. Chem. Res.

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“…It possesses a hexacyclic scaffold with six contiguous stereogenic centers, two quaternary centers, and an α,β,γ,δ-unsaturated carboxylic ester thus signifying a formidable synthetic challenge. Following our long-lasting interest in the synthesis of the Daphniphyllum alkaloids 31 – 33 , 51 , 52 , we now wish to report an asymmetric total synthesis of yuzurimine-type alkaloid, (+)-caldaphnidine J. Our approach is featured with a Pd-catalyzed regioselective hydroformylation that furnishes the critical aldehyde motif, and the construction of the 5/5 bicyclic system using a SmI 2 -promoted pinacol coupling and a one-pot Swern oxidation/ketene dithioacetal Prins reaction.…”

Section: Introductionmentioning

confidence: 99%

Asymmetric total synthesis of yuzurimine-type Daphniphyllum alkaloid (+)-caldaphnidine J

Guo

Zhang

et al. 2020

Nat Commun

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Ever since Hirata's report of yuzurimine in 1966, nearly fifty yuzurimine-type alkaloids have been isolated, which formed the largest subfamily of the Daphniphyllum alkaloids. Despite extensive synthetic studies towards this synthetically challenging and biologically intriguing family, no total synthesis of any yuzurimine-type alkaloids has been achieved to date. Here, the first enantioselective total synthesis of (+)-caldaphnidine J, a highly complex yuzuriminetype Daphniphyllum alkaloid, is described. Key transformations of this approach include a highly regioselective Pd-catalyzed hydroformylation, a samarium(II)-mediated pinacol coupling, and a one-pot Swern oxidation/ketene dithioacetal Prins reaction. Our approach paves the way for the synthesis of other yuzurimine-type alkaloids and related natural products.

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Robinson Annulation Applied to the Total Synthesis of Natural Products

et al. 2023

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The Robinson annulation is a significant reaction for the synthesis of α,β‐unsaturated ketone ring including the generation of two C−C bonds. It involves a Michael addition of a ketone and a methyl or ethyl vinyl ketone with subsequent intramolecular aldol condensation. Natural products and their structurally related analogues have historically made a major contribution to pharmacotherapy, particularly for cancer and infectious diseases. The Robinson annulation has frequently been employed as a vital step in the total synthesis of these important naturally occurring compounds and related complex biologically active products. In this review, we try to underscore the applications of the Robinson annulation in the total synthesis of biologically active natural products.

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Synthesis of the Core Structure of Daphnimacropodines

Cited by 15 publications

References 83 publications

Total Synthesis of Daphniphyllum Alkaloids: From Bicycles to Diversified Caged Structures

Total Synthesis of Daphniphyllum Alkaloids: From Bicycles to Diversified Caged Structures

Asymmetric total synthesis of yuzurimine-type Daphniphyllum alkaloid (+)-caldaphnidine J

Robinson Annulation Applied to the Total Synthesis of Natural Products

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