A Unified Approach for the Assembly of Atisine‐ and Hetidine‐type Diterpenoid Alkaloids: Total Syntheses of Azitine and the Proposed Structure of Navirine C

Liu, Jie; Ma, Dawei

doi:10.1002/ange.201803018

Cited by 19 publications

(2 citation statements)

References 53 publications

(28 reference statements)

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“…Of the biosynthetically related atisine-, hetidine-, and hetisine-type C 20 -diterpenoid alkaloids, the hexacyclic hetidine core has a characteristic C14–C20 linkage; besides the C14–C20 linkage, the hetisine core has an additional C6–N linkage, forming a complex heptacyclic framework. The unique biological profiles and structural complexity of C 20 -diterpenoid alkaloids render them highly sought-after synthetic targets. − Successful total syntheses of hetisine-type alkaloids have been reported by the groups of Muratake/Natsume, Gin, and Sarpong, as well as our group, reflecting considerable achievements toward total synthesis of various C 20 -diterpenoid alkaloids in recent years. − However, there has been limited success in the synthesis of the seemingly less complex hetidine-type alkaloids, despite considerable efforts having been made toward this subtype. , Guided by network analysis, Sarpong’s group accomplished a unified total synthesis of C 18 -, C 19 -, and C 20 -diterpenoid alkaloids ,,, and developed an elegant approach of Ga-catalyzed cycloisomerization to synthesize dihydronavirine, a structurally very similar analogue of navirine. , Baran’s group applied a two-phase synthetic strategy to synthesize the atisine alkaloids and construct the hetidine skeleton from a readily available ent -kaurane . Qin and Liu developed an efficient biomimetic approach to access the denudatine- and atisine-type alkaloids and the hetidine skeleton from an atisine-type precursor .…”

Section: Introductionmentioning

confidence: 99%

Asymmetric Total Synthesis of Hetidine-Type C₂₀-Diterpenoid Alkaloids: (+)-Talassimidine and (+)-Talassamine

et al. 2021

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Here, we report the first asymmetric total synthesis of (+)-talassimidine and (+)-talassamine, two hetidine-type C20-diterpenoid alkaloids. A highly regio- and diastereoselective 1,3-dipolar cycloaddition of an azomethine ylide yielded a chiral tetracyclic intermediate in high enantiopurity, thus providing the structural basis for asymmetric assembly of the hexacyclic hetidine skeleton. In this key step, the introduction of a single chiral center induces four new continuous chiral centers. Another key transformation is the dearomative cyclopropanation of the benzene ring and subsequent SN2-like ring opening of the resultant cyclopropane ring with water as a nucleophile, which not only establishes the B ring but also precisely installs the difficult-to-achieve equatorial C7–OH group.

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Section: Introductionmentioning

confidence: 99%

Asymmetric Total Synthesis of Hetidine-Type C₂₀-Diterpenoid Alkaloids: (+)-Talassimidine and (+)-Talassamine

et al. 2021

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“…5 The so-called Grignard reagent is capable of reacting with various electrophiles such as aldehydes, ketones, carbon dioxide, amides, and several more ( Figure 1 A), 6 opening facile access to valuable compounds, used in the synthesis of fine chemicals, pharmaceuticals and natural products. 6 , 7 …”

Section: Introductionmentioning

confidence: 99%

Strategies for the Photocatalytic Generation of Carbanion Equivalents for Reductant-Free C–C Bond Formations

Donabauer

König

2020

Acc. Chem. Res.

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Conspectus The use of photocatalysis in organic chemistry has encountered a surge of novel transformations since the start of the 21st century. The majority of these transformations are driven by the generation and subsequent reaction of radicals, owing to the intrinsic property of common photocatalysts to transfer single electrons from their excited state. While this is a powerful and elegant method to develop novel transformations, several research groups recently sought to further extend the toolbox of photocatalysis into the realm of polar ionic reactivity by the formation of cationic as well as anionic key reaction intermediates to furnish a desired product. Our group became especially interested in the photocatalytic formation of anionic carbon nucleophiles, as the overall transformation resembles classical organometallic reactions like Grignard, Barbier, and Reformatsky reactions, which are ubiquitous in organic synthesis with broad applications especially in the formation of valuable C–C bonds. Although these classical reactions are frequently applied, their use still bears certain disadvantages; one is the necessity of an (over)stoichiometric amount of a reducing metal. The reducing, low-valent, metal is solely applied to activate the starting material to form the organometallic carbanion synthon, while the final reaction product does generally not contain a metal species. Hence, a stoichiometric amount of metal salt is bound to be generated at the end of each reaction, diminishing the atom economy. The use of visible light as mild and traceless activation agent to drive chemical reactions can be a means to arrive at a more atom economic transformation, as a reducing metal source is avoided. Beyond this, the vast pool of photocatalytic activation methods offers the potential to employ easily available starting materials, as simple as unfunctionalized alkanes, to open novel and more facile retrosynthetic pathways. However, as mentioned above, photocatalysis is dominated by open-shell radical reactivity. With neutral radicals showing an intrinsically different reactivity than ionic species, novel strategies to form intermediates expressing a polar behavior need to be developed in order to achieve this goal. In the last couple of years, several methods toward this aim have been reported by our group and others. This Account aims to give an overview of the different existing strategies to photocatalytically form carbon centered anions or equivalents of those in order to form C–C bonds. As the main concept is to omit a stoichiometric reductant source (like a low-valent metal in classical organometallic reactions), only redox-neutral and reductant-free transformations were taken into closer consideration. We present selected examples of important strategies and try to illustrate the intentions and concepts behind the methods developed by our group and others.

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A Concise Total Synthesis of (−)‐Himalensine A

Chen

Guo

et al. 2019

Angewandte Chemie

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The daphniphyllum alkaloids are a structurally fascinating and remarkably diverse family of natural products. General strategies for the chemical synthesis of their challenging architectures are highly desirable for efficiently accessing these intriguing alkaloids and addressing their pharmaceutical potential. Herein, a concise strategy designed to provide general and diversifiable access to various daphniphyllum alkaloids is described and utilized in the asymmetric synthesis of (−)‐himalensine A, which was accomplished in 14 steps. Key features of this strategy include a Cu‐catalyzed nitrile hydration, a Heck reaction to construct the challenging 2‐azabicyclo[3.3.1]nonane motif, a Meinwald rearrangement reaction, six, pot‐economic reactions, and the minimal use of protecting groups, which significantly improved the overall synthetic efficiency.

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A Unified Approach for the Assembly of Atisine‐ and Hetidine‐type Diterpenoid Alkaloids: Total Syntheses of Azitine and the Proposed Structure of Navirine C

Cited by 19 publications

References 53 publications

Asymmetric Total Synthesis of Hetidine-Type C₂₀-Diterpenoid Alkaloids: (+)-Talassimidine and (+)-Talassamine

Asymmetric Total Synthesis of Hetidine-Type C₂₀-Diterpenoid Alkaloids: (+)-Talassimidine and (+)-Talassamine

Strategies for the Photocatalytic Generation of Carbanion Equivalents for Reductant-Free C–C Bond Formations

A Concise Total Synthesis of (−)‐Himalensine A

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A Unified Approach for the Assembly of Atisine‐ and Hetidine‐type Diterpenoid Alkaloids: Total Syntheses of Azitine and the Proposed Structure of Navirine C

Cited by 19 publications

References 53 publications

Asymmetric Total Synthesis of Hetidine-Type C20-Diterpenoid Alkaloids: (+)-Talassimidine and (+)-Talassamine

Asymmetric Total Synthesis of Hetidine-Type C20-Diterpenoid Alkaloids: (+)-Talassimidine and (+)-Talassamine

Strategies for the Photocatalytic Generation of Carbanion Equivalents for Reductant-Free C–C Bond Formations

A Concise Total Synthesis of (−)‐Himalensine A

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Asymmetric Total Synthesis of Hetidine-Type C₂₀-Diterpenoid Alkaloids: (+)-Talassimidine and (+)-Talassamine

Asymmetric Total Synthesis of Hetidine-Type C₂₀-Diterpenoid Alkaloids: (+)-Talassimidine and (+)-Talassamine