A Concise Total Synthesis of (±)-Stepharine and (±)-Pronuciferine

Chen, Ruimin; Jia, Shihu; Man, Yuning; Cheng, Hong‐Gang; Zhou, Qianghui

doi:10.1055/a-1984-0755

Cited by 7 publications

(4 citation statements)

References 37 publications

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“…Isolated from Neilzlmbo nucifera by Bernauer and co-workers in 1963, (±)-stepharine and (±)-pronuciferine are two representative members of proaporphine alkaloids featuring a 6–6–5–6 ring system, including a THIQ moiety and a spiro-cyclohexadienone skeleton. A retrosynthetic analysis is presented in Scheme A . We conceived that the spiro-cyclohexadienone scaffold could be assembled from 1-methylene-THIQ 53 via an oxidative dearomatization followed by reduction, referring to Honda’s work .…”

Section: Application In Total Synthesismentioning

confidence: 99%

“…A retrosynthetic analysis is presented in Scheme 14A. 51 We conceived that the spirocyclohexadienone scaffold could be assembled from 1methylene-THIQ 53 via an oxidative dearomatization followed by reduction, referring to Honda's work. 52 The crucial intermediate 53 could be constructed through an Au-catalyzed 6-exo-dig cyclization of 2′-alkynylaryl-2-ethylamine 54.…”

Section: Total Synthesis Of Dactyllactone Amentioning

confidence: 99%

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Benzo-Fused-Ring Toolbox Based on Palladium/Norbornene Cooperative Catalysis: Methodology Development and Applications in Natural Product Synthesis

2023

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Metrics & MoreArticle Recommendations CONSPECTUS: Benzo-fused skeletons are ubiquitous in agrochemicals, medicines, natural products, catalysts, and other organic function materials. The assembly of these skeletons in an efficient manner is an actively explored field in organic synthesis. Palladium/norbornene (Pd/NBE) cooperative catalysis is a powerful tool for the expeditious assembly of polysubstituted arenes through bisfunctionalization of the ortho and ipso positions of aryl iodides in one operation.Owing to the efforts of Lautens, Catellani, and others, an array of Pd/NBEpromoted annulations for the syntheses of diversified benzo-fused rings have been developed. However, these methods have not been broadly applied in total synthesis yet.Our group is interested in efficient and practical total synthesis of biologically active molecules. In the past 7 years, we have been devoted to the development of new annulation strategies for the assembly of common benzo-fused skeletons through Pd/NBE-promoted reactions of aryl iodides with novel bifunctional reagents. In this Account, we summarize our laboratory's systematic efforts in this direction. First, readily available epoxides and aziridines were exploited as versatile bifunctional alkylating reagents, which enables quick assembly of a series of valuable benzo-fused heterocycles, including isochromans, dihydrobenzofurans, 1,3-cis-tetrahydroisoquinolines (THIQs), 1,3-trans-THIQs, etc. Second, a convergent access to 5−7-membered benzo-fused carbocycles (including indanes and tetrahydronaphthalenes) was developed by Pd/NBE-promoted annulation of aryl iodides with simple olefinic alcohol-containing alkylating reagents. Third, a Pd/NBE-promoted annulation between aryl iodides and cyclohexanone-containing amination reagents was developed for the construction of benzo-fused N-containing bridged scaffolds. Thus, we have established a practical and versatile toolbox for the quick assembly of diversified benzo-fused skeletons. These new annulation reactions are of high chemo-, regio-, and stereoselectivities with good step and atom economy. Moreover, they are able to rapidly increase molecular complexity from simple building blocks. Finally, their synthetic value has been demonstrated by immediate adoption in several efficient total syntheses of medicines and complex natural products. Compared to conventional synthetic logics, the Pd/NBE-promoted annulation toolbox allows the development of highly convergent strategies, which significantly improves the overall synthetic efficiency.We believe the results presented in this Account will have significant implications beyond our research. It can be envisaged that new Pd/NBE-promoted annulations as well as new applications in complex total synthesis will be revealed in the near future.

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Section: Application In Total Synthesismentioning

confidence: 99%

Section: Total Synthesis Of Dactyllactone Amentioning

confidence: 99%

Benzo-Fused-Ring Toolbox Based on Palladium/Norbornene Cooperative Catalysis: Methodology Development and Applications in Natural Product Synthesis

2023

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“…1). 1 Thus, great efforts have been devoted to the synthesis of functionalized spiro-cyclohexadienones. 2 Several strategies for the efficient construction of spiro-cyclohexadienones have been reported in recent years.…”

Section: Introductionmentioning

confidence: 99%

Palladium-catalyzed and ligand-controlled divergent cycloadditions of vinylidenecyclopropane-diesters with para-quinone methides enabled by zwitterionic π-propargyl palladium species

Shen,

Long,

Shi

et al. 2024

Org. Chem. Front.

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“…For instance, spirooxindole A is a crucial intermediate in synthesizing the potent and selective vasopressin inhibitor SR121463A C (Figure 1) 2 . Similarly, spirodihydroquinolone B is essential in preparing azagalanthamine D. 3 Furthermore, spindomycine B E, featuring a spirocyclohexadienone linked to oxindole, acts as a Bcr-Abl inhibitor, 4 while spirocyclohexadienones tethered to the tetrahydroisoquinoline molecule F (Stepharine) exhibit antihypertensive activity 5 (Figure 1). Pyrazolone tethered to the spirocyclohexadienone core G shows anti-tumor activity against cancer cells.…”

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confidence: 99%

PIFA-Mediated Intramolecular Dearomatization of Phenol-Tethered 1,2-Diazoles: Synthesis of Spirocyclohexadienone-pyrazolo[3,4-b]piperidinones

Natarajan,

Bachhaley,

Tripathy

et al. 2024

Synthesis

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In recent years, the significance of spirocyclic motifs in drug discovery has increased, owing to their unique ability to engage biological targets. We present the first example of PIFA-mediated dearomative spirocyclization of phenol-tethered pyrazoles, highlighting intramolecular trapping by the pyrazole moiety. This method efficiently affords a variety of spirocyclohexadienone pyrazolo[3,4-b]piperidinones with yields of up to 82%. Mechanistic studies reveal that the dearomatization process involves a cationic intermediate.

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A Concise Total Synthesis of (±)-Stepharine and (±)-Pronuciferine

Cited by 7 publications

References 37 publications

Benzo-Fused-Ring Toolbox Based on Palladium/Norbornene Cooperative Catalysis: Methodology Development and Applications in Natural Product Synthesis

Benzo-Fused-Ring Toolbox Based on Palladium/Norbornene Cooperative Catalysis: Methodology Development and Applications in Natural Product Synthesis

Palladium-catalyzed and ligand-controlled divergent cycloadditions of vinylidenecyclopropane-diesters with para-quinone methides enabled by zwitterionic π-propargyl palladium species

PIFA-Mediated Intramolecular Dearomatization of Phenol-Tethered 1,2-Diazoles: Synthesis of Spirocyclohexadienone-pyrazolo[3,4-b]piperidinones

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