A Concise Total Synthesis of (±)-Minfiensine

Liu, Peijun; Wang, Juan; Zhang, Jiancun; Qiu, Fayang G.

doi:10.1021/ol2027224

Cited by 54 publications

(31 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was found that the regioselectivity of the ring‐opening reaction highly depends on the reagents used (Table ). Treatment of epoxide 12 with TMSOTf/DBU led to only minor conversion, and the undesired regioisomer 14 was the major product (entry 1). To increase the selectivity by favoring proton abstraction at the less hindered C2 of the ring system, a sterically hindered Lewis acid/base pair, Al(O i Pr) 3 was employed .…”

Section: Figurementioning

confidence: 99%

Total Synthesis of (+)‐Minfiensine: Construction of the Tetracyclic Core Structure by an Asymmetric Cascade Cyclization

2016

View full text Add to dashboard Cite

A new method for one-step construction of the tetracyclic core structure of the indole alkaloid (+)-minfiensine was developed utilizing a palladium-catalyzed asymmetric indole dearomatization/iminium cyclization cascade. An efficient total synthesis of (+)-minfiensine was realized using this strategy. The present method enables access to the common core structure of a series of monoterpene indole alkaloids, such as vincorine, echitamine, and aspidosphylline A.Monoterpeneindolealkaloidsconstitutealargecategoryof natural products.[1] Among them, an array of strychnos and akuammiline alkaloids are quite attractive because of their unique cagelike structure and promising biological activity (Figure 1). [1, 2] These natural products share a common core structure, the 4a,9a-heterocycle-fused tetrahydrocarbazole skeleton, which bears two adjacent quaternary stereocenters.To address the synthetic challenges posed by these complex alkaloids, the development of strategies for efficient asymmetric assembly of the core structure is in demand. During the past decade, these monoterpene indole alkaloids attracted much research interest from the synthetic community. As a result, a large number of total syntheses have been reported. [3][4][5] However, the strategies that rendered efficient asymmetric syntheses are still limited. [3a,b,d, 4d, 5b,c] For instance, for a representative member in these alkaloids, (+)-minfiensine, only two catalytic asymmetric methods have been reported to date for achieving its total synthesis (Scheme 1). [3a,b,d] Given the effort devoted to the syntheses of these important alkaloids, the discovery of efficient and flexible new strategies for asymmetric assembly of the core framework would promote advances in this field.We sought to develop a new and straightforward approach to (+)-minfiensine based on the catalytic asymmetric dearomatization of indole (Scheme 1). It is envisioned that intramolecular asymmetric allylic substitution of the indole substrate A gives the intermediate C, which upon in situ trapping of the generated iminium ion [3a-d,g, 6, 8f] affords the tetracycle D, having the desired core structure. The advantage of this design is that the exocyclic C = C bond formed by allylic alkylation largely facilitates creation of the hydroxymethyl functionality in (+)-minfiensine. To our surprise, although palladium- [7] and iridium-catalyzed [8] asymmetric allylic alkylations of indole have been well established, [9] very little effort was made to utilize the synthetic power of those protocols in Figure 1. Representative strychnos and akuammiline alkaloids and their common core structure. Scheme 1. Previous asymmetric syntheses of (+)-minfiensine and the designed asymmetric cascade cyclization strategy. Boc = tert-butoxycarbonyl, PMB = para-methoxybenzyl.

show abstract

Section: Figurementioning

confidence: 99%

Total Synthesis of (+)‐Minfiensine: Construction of the Tetracyclic Core Structure by an Asymmetric Cascade Cyclization

2016

View full text Add to dashboard Cite

show abstract

“…Lapidilectine B, grandilodine C [22], and lundurine B exhibit multidrug resistance (MDR) in vincristine-resistant KB cancer cells [23–24]. Minfiensine alkaloid [25–31] containing a novel 1,2,3,4-tetrahydrocarbazole ring skeleton shows anticancer activity [32]. König and co-workers identified some propellane derivatives as cannabinoid CB 1 receptor antagonists [33], which are potential drugs for the treatment of schizophrenia and alcohol addiction [34].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of indole-based propellane derivatives via Weiss–Cook condensation, Fischer indole cyclization, and ring-closing metathesis as key steps

Kotha¹,

Chinnam²,

Tiwari³

2013

Beilstein J. Org. Chem.

View full text Add to dashboard Cite

show abstract

“…Based on the retrosynthetic analysis,o ur synthesis of (+ +)-flavisiamine F( 1)c ommenced with the protected carbazolone 5,w hich was prepared from carbazole-3,2'-[1,3]dioxolane [10] by introducing the phenylsulfonyl group in basic conditions followed by acidic deprotection. Reaction with LiHMDS and Hendrickson-McMurray reagent afforded the triflate 6 as shown in Scheme 2.…”

mentioning

confidence: 99%

Enantioselective Total Synthesis of (+)‐Flavisiamine F via Late‐Stage Visible‐Light‐Induced Photochemical Cyclization

et al. 2019

View full text Add to dashboard Cite

The structural features Kopsia alkaloids,i np articular multiple all-carbon quaternary stereocenters in ac aged and strained polycyclic skeleton, poses particular challenges for enantioselective total synthesis.Herein, we reported the first total synthesis of (+ +)-flavisiamine F. The synthetic approach involved ar oom-temperature Overman rearrangement for introducing the chiral amine at C21, aT MS-promoted ketal Claisen rearrangement for constructing the all-carbon quaternary stereocenter at C20, and alate-stage visible-light-induced photochemical cyclization for establishing the all-carbon quaternary stereocenter at C7.

show abstract

A Concise Total Synthesis of (±)-Minfiensine

Cited by 54 publications

References 19 publications

Total Synthesis of (+)‐Minfiensine: Construction of the Tetracyclic Core Structure by an Asymmetric Cascade Cyclization

Total Synthesis of (+)‐Minfiensine: Construction of the Tetracyclic Core Structure by an Asymmetric Cascade Cyclization

Synthesis of indole-based propellane derivatives via Weiss–Cook condensation, Fischer indole cyclization, and ring-closing metathesis as key steps

Enantioselective Total Synthesis of (+)‐Flavisiamine F via Late‐Stage Visible‐Light‐Induced Photochemical Cyclization

Contact Info

Product

Resources

About