Total Synthesis of Yuzurine-type Alkaloid Daphgraciline

Li, Lixuan; Min, Long; Yao, Tian-Bing; Ji, Shu-Xiao; Qiao, Chuang; Tian, Peilin; Sun, Jianwei; Li, Chuang‐Chuang

doi:10.1021/jacs.2c09548

“…[1] Among them, Daphniphyllum alkaloids isolated from plants of the genus Daphniphyllum have attracted great interest of synthetic chemists [2] for their structural complexities and broad biological activities such as anticancer, anti-human immunodeficiency virus (HIV), antiox-idation, and vasorelaxant activities. [2a, 3] Since Heathcock and co-workers completed several impressive syntheses of Daphniphyllum alkaloids via a remarkable tetracyclization process (Figure 1), [4] the groups of Carreira, [5] A. Li, [6] Smith, [7] Fukuyama, [8] Hanessian, [9] Dixon, [10] Qiu, [11] Xu, [12] Gao, [13] Sarpong, [14] C. Li, [15] Lu, [16] C.-C. Li, [17] and our group [18] successively accomplished the total syntheses of a series of Daphniphyllum alkaloids, which have promoted the development of powerful methodologies and strategies in this area.…”

Section: Introductionmentioning

confidence: 99%

Divergent Total Syntheses of (−)‐Daphnezomines A and B and (+)‐Dapholdhamine B

Su

¹

,

Lin

²

,

Zhai

³

2023

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The daphnezomine A-type subfamily of Daphniphyllum alkaloids structurally features a unique aza-adamantane core skeleton and anticipates efficient strategies for completing their syntheses to thoroughly investigate their biological activities. Herein, divergent total syntheses of (À )-daphnezomines A and B and (+)-dapholdhamine B have been accomplished in 16-20 steps from a known epoxide via rapid construction of a common core intermediate. The present work features a Ti-mediated radical cyclization to establish the azabicyclo[3.3.1]nonane ring system, an intramolecular Heck reaction to install the bridgehead all-carbon quaternary stereocenter, a tandem deprotection/reduction/keto amine-carbinolamine tautomerization to furnish the aza-adamantane backbone, and an NIS-promoted 6-endo-trig aminocyclization to assemble the (+)-dapholdhamine B backbone.

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“…[1] Among them, Daphniphyllum alkaloids isolated from plants of the genus Daphniphyllum have attracted great interest of synthetic chemists [2] for their structural complexities and broad biological activities such as anticancer, anti-human immunodeficiency virus (HIV), antiox-idation, and vasorelaxant activities. [2a, 3] Since Heathcock and co-workers completed several impressive syntheses of Daphniphyllum alkaloids via a remarkable tetracyclization process (Figure 1), [4] the groups of Carreira, [5] A. Li, [6] Smith, [7] Fukuyama, [8] Hanessian, [9] Dixon, [10] Qiu, [11] Xu, [12] Gao, [13] Sarpong, [14] C. Li, [15] Lu, [16] C.-C. Li, [17] and our group [18] successively accomplished the total syntheses of a series of Daphniphyllum alkaloids, which have promoted the development of powerful methodologies and strategies in this area.…”

Section: Introductionmentioning

confidence: 99%

Divergent Total Syntheses of (−)‐Daphnezomines A and B and (+)‐Dapholdhamine B

Su

¹

,

Lin

²

,

Zhai

³

2023

Angewandte Chemie

0

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The daphnezomine A‐type subfamily of Daphniphyllum alkaloids structurally features a unique aza‐adamantane core skeleton and anticipates efficient strategies for completing their syntheses to thoroughly investigate their biological activities. Herein, divergent total syntheses of (−)‐daphnezomines A and B and (+)‐dapholdhamine B have been accomplished in 16–20 steps from a known epoxide via rapid construction of a common core intermediate. The present work features a Ti‐mediated radical cyclization to establish the azabicyclo[3.3.1]nonane ring system, an intramolecular Heck reaction to install the bridgehead all‐carbon quaternary stereocenter, a tandem deprotection/reduction/keto amine‐carbinolamine tautomerization to furnish the aza‐adamantane backbone, and an NIS‐promoted 6‐endo‐trig aminocyclization to assemble the (+)‐dapholdhamine B backbone.

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“…(2022); [29] (+)‐caldaphnidine J (2020) by Guo et al. ; [30] daphgraciline (2022) by Li et al [31] . etc.…”

Section: Introductionmentioning

confidence: 99%

Synthetic Studies to exo‐Ring‐Junction based Fused 5/5/n‐Tricyclic Systems: Access to A, B, C‐Ring System of Longeracinphyllin A, Himalenine D, and Daphnipaxiamine A.

Kotha

¹

,

Agrawal

²

,

Keesari

³

2023

Asian J Org Chem

1

0

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We report a short synthetic approach to various tricyclic systems that are present in several diquinane‐based natural products starting with a readily available exo‐dicyclopentadiene‐1‐one. To this end, we have successfully assembled a fused 5/5/7‐tricyclic enone via ring‐rearrangement metathesis as a key step. The strategy has been further extended to synthesize the 1,3‐dihydroxy and then 1‐keto‐3‐hydroxy derivatives by utilizing regio‐ and stereoselective epoxidation and ring‐rearrangement metathesis reactions as key steps. All these target compounds are found to be present in diquinane‐based natural products such as longeracinphyllins A, himalenine D and daphnipaxianine A, etc. Moreover, the newly synthesized tricyclic compounds matches the exact ring‐junction stereochemistry (5/5‐exo) of these natural products. Hence, the synthetic studies disclosed here may be useful in the synthesis of biologically significant natural products and in the drug design. The newly synthesized molecules were characterized by NMR and HRMS data. Some of these structures were confirmed by a single crystal X‐ray diffraction studies.

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Total Synthesis of Yuzurine-type Alkaloid Daphgraciline

Cited by 17 publications

References 91 publications

Divergent Total Syntheses of (−)‐Daphnezomines A and B and (+)‐Dapholdhamine B

Divergent Total Syntheses of (−)‐Daphnezomines A and B and (+)‐Dapholdhamine B

Divergent Total Syntheses of (−)‐Daphnezomines A and B and (+)‐Dapholdhamine B

Synthetic Studies to exo‐Ring‐Junction based Fused 5/5/n‐Tricyclic Systems: Access to A, B, C‐Ring System of Longeracinphyllin A, Himalenine D, and Daphnipaxiamine A.

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