Protecting-Group-Free Total Synthesis of (−)-Lycopodine via Phosphoric Acid Promoted Alkyne Aza-Prins Cyclization

Ma, Dawei; Zhong, Zhuliang; Liu, Zaimin; Zhang, Mingjie; Xu, Shiyan; Xu, Deyang; Song, Dengpeng; Xie, Xingang; She, Xuegong

doi:10.1021/acs.orglett.6b02072

Cited by 35 publications

(25 citation statements)

References 72 publications

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“…[ 17 ] We commenced our synthesis from the Wade's enone, which was easily prepared in large scale in 4 steps from R ‐pulegone (Scheme 7). [ 18 ] Michael addition of propargylindium reagent to Wade's enone followed by an acid‐promoted one‐pot translactamation/condensation reaction delivered two bicyclic alkyne‐ enamides 30 in high yields. After an extensive screening of the optimal acid promoters, the key aza ‐Prins cyclization of 30 smoothly proceeded to give the desired tricyclic compounds 33a and 33b in 90% and 96% yields, respectively, under the weaker Brōnsted acids conditions (HCO 2 H/85% H 3 PO 4 , 1 : 1).…”

Section: Total Syntheses Of Lycopodium Alkaloidsmentioning

confidence: 99%

Concise Total Syntheses of Bioactive Alkaloids Enabled by Development or Application of Cascade Reactions: A Personnel Adventure

Xie

She

2021

Chin. J. Chem.

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What is the most favorite and original chemistry developed in your research group? Total synthesis of bioactive natural products is the most favorite chemistry in my research group and development or application of new strategies to improve the synthetic efficiency is the most original chemistry developed in my research group. How do you get into this specific field? Could you please share some experiences with our readers? My PhD project was total synthesis of bioactive natural lignans and I devoted myself into synthetic methodology development during my postdoctoral research period. In my opinion, a highly efficient synthetic method will greatly shorten the synthetic route and improve its efficiency for a target-oriented total synthesis. On the other hand, target-oriented total synthesis is the best platform to evaluate the practical value of a synthetic method. So I choose total synthesis of natural products and target-oriented synthetic methodology development as my research fields when I began my independent research. How do you supervise your students? When the students start their projects, I discuss the research subjects with them once a month. Every Saturday night we hold a group meeting to learn and discuss the most recent published literatures related to our research. I give more encouragement when the students meet difficulties in their research. Then we try to solve the difficulties together. What is the most important personality for scientific research? In my view, diligence and persistence are the most important personalities for scientific research. What's your hobby? What's your favorite book(s)? Reading. My favorite book is Sapiens-a brief history of humankind. How do you keep balance between research and family? I usually spend six days (from Monday to Saturday) on research work. On Sunday I will cook some delicious food and enjoy it with my family. My wife understands and supports my work very well. She has done a lot for our family.

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Section: Total Syntheses Of Lycopodium Alkaloidsmentioning

confidence: 99%

Concise Total Syntheses of Bioactive Alkaloids Enabled by Development or Application of Cascade Reactions: A Personnel Adventure

Xie

She

2021

Chin. J. Chem.

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“…She and co-workers used the alkynyl aza-Prins cyclization as the key step of their total synthesis of (-)-lycopodine (135) (Scheme 30). 56 Beginning with 132, the aza-Prins reaction is initiated under aqueous acidic conditions by protonation of the enamide moiety to reveal the N-acyliminium electrophile 133. This species then undergoes distal cyclization by the nucleophilic alkyne.…”

Section: Reviewmentioning

confidence: 99%

Alkynyl Prins and Alkynyl Aza-Prins Annulations: Scope and Synthetic Applications

Abdul-Rashed¹,

Holt²,

Frontier³

2020

Synthesis

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This review focuses on alkynyl Prins and alkynyl aza-Prins cyclization processes, which involve intramolecular coupling of an alkyne with either an oxocarbenium or iminium electrophile. The oxocarbenium or iminium species can be generated through condensation- or elimination-type processes, to achieve an overall bimolecular annulation that enables the synthesis of both oxygen- and nitrogen-containing saturated heterocycles with different ring sizes and substitution patterns. Also discussed are cascade processes in which alkynyl Prins heterocyclic adducts react to trigger subsequent pericyclic reactions, including [4+2] cycloadditions and Nazarov electrocyclizations, to rapidly construct complex small molecules. Finally, examples of the use of alkynyl Prins and alkynyl aza-Prins reactions in the synthesis of natural products are described. The review covers the literature through the end of 2019.1 Introduction1.1 Alkyne-Carbonyl Coupling Pathways1.2 Coupling/Cyclization Cascades Using the Alkynyl Prins Reaction2 Alkynyl Prins Annulation (Oxocarbenium Electrophiles)2.1 Early Work2.2 Halide as Terminal Nucleophile2.3 Oxygen as Terminal Nucleophile2.4 Arene as Terminal Nucleophile (Intermolecular)2.5 Arene Terminal Nucleophile (Intramolecular)2.6 Cyclizations Terminated by Elimination3 Synthetic Utility of Alkynyl Prins Annulation3.1 Alkynyl Prins-Mediated Synthesis of Dienes for a [4+2] Cyclo- addition-Oxidation Sequence3.2 Alkynyl Prins Cyclization Adducts as Nazarov Cyclization Precursors3.3 Alkynyl Prins Cyclization in Natural Product Synthesis4 Alkynyl Aza-Prins Annulation4.1 Iminium Electrophiles4.2 Activated Iminium Electrophiles5 Alkynyl Aza-Prins Cyclizations in Natural Product Synthesis6 Summary and Outlook

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“…Very recently She's group succeeded in the asymmetric total synthesis of two Lycopodium alkaloids, with tetracyclic cores: (–)‐lycopodine ( 140 ) and (–)‐lycospidine A ( 141 ), which have been used in Chinese folk medicine as analgesics, for example . The main difference between the core structures of the two natural products resides in the A ring: in (–)‐lycopodine this is a six‐membered ring, whereas in (–)‐lycospidine A it is five‐membered (Scheme ).…”

Section: Synthesis Of Natural Products and Bioactive Moleculesmentioning

confidence: 99%

The Aza‐Prins Reaction in the Synthesis of Natural Products and Analogues

et al. 2017

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International audienceThe classical Prins cyclization reaction has been one of the most studied reactions during the last two decades and it has found many applications in key steps of natural product syntheses, especially for products containing pyran units and related structures in their core skeletons. The nitrogen-based version of the Prins reaction, aza-Prins cyclization, has found its own relevance in organic synthesis owing to the fact that it gives direct access to piperidines, which are even more widespread in natural products and in drugs. Even though the potential scope of the reaction is vast, and despite it having afforded significant progress in the synthesis of various azaheterocycles, its applications in the field of natural product synthesis is massively underdeveloped in comparison with the classical Prins reaction. A compilation of the applications of azaPrins cyclization in the preparation of natural products and selected analogues, especially compounds of potential biological interest, is presented, with emphasis placed on the key roles of this reaction in the total synthesis of these products

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Protecting-Group-Free Total Synthesis of (−)-Lycopodine via Phosphoric Acid Promoted Alkyne Aza-Prins Cyclization

Cited by 35 publications

References 72 publications

Concise Total Syntheses of Bioactive Alkaloids Enabled by Development or Application of Cascade Reactions: A Personnel Adventure

Concise Total Syntheses of Bioactive Alkaloids Enabled by Development or Application of Cascade Reactions: A Personnel Adventure

Alkynyl Prins and Alkynyl Aza-Prins Annulations: Scope and Synthetic Applications

The Aza‐Prins Reaction in the Synthesis of Natural Products and Analogues

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