A three-component coupling approach to the ACE-ring substructure of C19-diterpene alkaloids

Minagawa, Kosuke; Urabe, Daisuke; Inoue, M.

doi:10.1038/ja.2017.69

“…In 2017, Inoue and co-workers disclosed a three-component coupling approach to append the AE ring systems to the C ring of C 19 -diterpenoid alkaloids in an expedient manner (Scheme 21). 90 The strategy utilized a radical-polar crossover cascade initiated with Et 3 B/O 2 and iodide 291 to form a bridgehead radical that first underwent conjugate addition with enone 292 on the opposite side of the OTBS substituent. The boron enolate intermediate 293 then underwent an aldol addition with alkynal 294 via the sixmembered transition state 295 to form the coupled product 296.…”

Section: Review Syn Thesismentioning

confidence: 99%

Recent Advances Towards Syntheses of Diterpenoid Alkaloids

Dank¹,

Sanichar²,

Choo³

et al. 2019

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The diterpenoid alkaloids serve as a rich source of synthetic targets for organic chemists, due to the intriguing structure of the overlapping ring systems, along with biological activities commonly associated with compounds of this group. Fifteen total syntheses and numerous synthetic studies towards construction of ring fragments have been reported since 2010. This review article gives a brief overview of diterpenoid alkaloids and summarizes the recent synthetic efforts.1 Introduction1.1 Structural Classification and Biosynthetic Origin1.2 Structure Elucidation of the Aconitum Alkaloids2 Total Syntheses2.1 C18-Diterpenoid Alkaloids2.2 C19-Diterpenoid Alkaloids2.3 C20-Diterpenoid Alkaloids3 Strategies To Synthesize Ring Systems3.1 Radical-Based Cyclizations3.2 Ruthenium-Mediated Enyne Cycloisomerization3.3 Reductive Coupling3.4 Diels–Alder Reactions3.5 Oxidative Dearomatization/Diels–Alder Sequence3.6 Transannular Aziridation3.7 Intramolecular [5+2] Cycloaddition3.8 Miscellaneous4 Conclusion

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“…Synthetic chemists have been inspired to invent novel synthetic strategies to overcome the daunting chemical challenges posed by these molecules. [6,7] These strategies led to creative solutions enabling the total syntheses of seven C 18and C 19 -diterpenoid alkaloids with various numbers of oxygen functionalities (Figure 1). These include the syntheses of 1 (5 oxygen functionalities,4 3s teps,l ongest linear sequence), chasmanine (6 oxygen functionalities,5 6s teps), and 13desoxydelphonine (6 oxygen functionalities,5 7s teps) by the Wiesner group in the 1970s, [8] neofinaconitine (5 oxygen functionalities,3 4s teps) by the Gin group in 2013, [9] weisaconitine D( 4o xygen functionalities,3 3s teps) and liljestrandinine (4 oxygen functionalities,3 1s teps) by the Sarpong group in 2015, [10] and cardiopetaline (3 oxygen functionalities,3 3o r2 7s teps) by the Fukuyama group in 2016.…”

Section: Introductionmentioning

confidence: 99%

Total Synthesis of Talatisamine

Kamakura

¹

,

Todoroki

²

,

Urabe

³

et al. 2019

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Talatisamine (1) is a member of the C19‐diterpenoid alkaloid family, and exhibits K+ channel inhibitory and antiarrhythmic activities. The formidable synthetic challenge that 1 presents is due to its highly oxidized and intricately fused hexacyclic 6/7/5/6/6/5‐membered‐ring structure (ABCDEF‐ring) with 12 contiguous stereocenters. Here we report an efficient synthetic route to 1 by the assembly of two structurally simple fragments, chiral 6/6‐membered AE‐ring 7 and aromatic 6‐membered D‐ring 6. AE‐ring 7 was constructed from 2‐cyclohexenone (8) through fusing an N‐ethylpiperidine ring by a double Mannich reaction. After coupling 6 with 7, an oxidative dearomatization/Diels–Alder reaction sequence generated fused pentacycle 4 b. The newly formed 6/6‐membered ring system was then stereospecifically reorganized into the 7/5‐membered BC‐ring of 3 via a Wagner–Meerwein rearrangement. Finally, Hg(OAc)2 induced an oxidative aza‐Prins cyclization of 2, thereby forging the remaining 5‐membered F‐ring. The total synthesis of 1 was thus accomplished by optimizing and orchestrating 33 transformations from 8.

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“…Synthetic chemists have been inspired to invent novel synthetic strategies to overcome the daunting chemical challenges posed by these molecules. [6,7] These strategies led to creative solutions enabling the total syntheses of seven C 18and C 19 -diterpenoid alkaloids with various numbers of oxygen functionalities (Figure 1). These include the syntheses of 1 (5 oxygen functionalities,4 3s teps,l ongest linear sequence), chasmanine (6 oxygen functionalities,5 6s teps), and 13desoxydelphonine (6 oxygen functionalities,5 7s teps) by the Wiesner group in the 1970s, [8] neofinaconitine (5 oxygen functionalities,3 4s teps) by the Gin group in 2013, [9] weisaconitine D( 4o xygen functionalities,3 3s teps) and liljestrandinine (4 oxygen functionalities,3 1s teps) by the 19 -diterpenoid alkaloids.…”

Section: Introductionmentioning

confidence: 99%

Total Synthesis of Talatisamine

Kamakura

¹

,

Todoroki

²

,

Urabe

³

et al. 2019

Self Cite

View full text Add to dashboard Cite

Talatisamine (1) is a member of the C19‐diterpenoid alkaloid family, and exhibits K+ channel inhibitory and antiarrhythmic activities. The formidable synthetic challenge that 1 presents is due to its highly oxidized and intricately fused hexacyclic 6/7/5/6/6/5‐membered‐ring structure (ABCDEF‐ring) with 12 contiguous stereocenters. Here we report an efficient synthetic route to 1 by the assembly of two structurally simple fragments, chiral 6/6‐membered AE‐ring 7 and aromatic 6‐membered D‐ring 6. AE‐ring 7 was constructed from 2‐cyclohexenone (8) through fusing an N‐ethylpiperidine ring by a double Mannich reaction. After coupling 6 with 7, an oxidative dearomatization/Diels–Alder reaction sequence generated fused pentacycle 4 b. The newly formed 6/6‐membered ring system was then stereospecifically reorganized into the 7/5‐membered BC‐ring of 3 via a Wagner–Meerwein rearrangement. Finally, Hg(OAc)2 induced an oxidative aza‐Prins cyclization of 2, thereby forging the remaining 5‐membered F‐ring. The total synthesis of 1 was thus accomplished by optimizing and orchestrating 33 transformations from 8.

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A three-component coupling approach to the ACE-ring substructure of C19-diterpene alkaloids

Cited by 11 publications

References 39 publications

Recent Advances Towards Syntheses of Diterpenoid Alkaloids

Recent Advances Towards Syntheses of Diterpenoid Alkaloids

Total Synthesis of Talatisamine

Total Synthesis of Talatisamine

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