Enantiospecific total synthesis of the ajmaline related alkaloids (-)-suaveoline, (-)-raumacline, and (-)-Nb-methylraumacline

Fu, Xiaoyong; Cook, James M.

doi:10.1021/ja00043a043

Cited by 59 publications

(35 citation statements)

References 7 publications

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“…Consequently, as an important subject of biology-oriented synthesis (BIOS) 11,12 , these Nbridged [3.3.1] ring systems are arguably one of the most versatile classes of target scaffolds towards developing and discovering smallmolecule drugs and/or their leading compounds, which have been fascinated and pursued by both synthetic and pharmaceutical chemists for decades 7,13,14 . Synthetic access to these (pseudo-)natural compounds was pioneered by Cook and co-workers, who have accomplished very elegant total synthesis of several indole alkaloids with this structural feature by using Dieckmann condensation to construct the N-bridged framework [13][14][15][16] . Besides, efficient strategies also include biomimetic synthesis and olefin metathesis by the Martin group 17,18 , a [5 + 2] cycloaddition/ring enlargement by the Gaich group 19,20 , and other methods [21][22][23] .…”

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confidence: 99%

“…Moreover, only sporadic examples that disclosed the synthesis of chiral azabicyclo [3.3.1]nonane compounds have been available so far (Fig. 1b), which utterly relied on utilizing chiral auxiliary 24 or employing chiral starting materials [14][15][16][17][18][19][20][21][22][23] , respectively. To the best of our knowledge, the catalytic asymmetric protocol for constructing such ring systems has never been reported to date, which remains a tremendous challenge and long-standing assignment in modern synthetic chemistry.…”

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confidence: 99%

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Asymmetric synthesis of N-bridged [3.3.1] ring systems by phosphonium salt/Lewis acid relay catalysis

Tan

Shen

et al. 2022

Nat Commun

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Optically pure pseudo-natural products (PNPs), particularly exemplified by azabicyclo[3.3.1]nonane molecules and their analogs provide an attractive platform for structure−activity relationship studies, and also lead new compound discovery in drug development. However, there are currently no examples of guiding catalytic asymmetric strategies available to construct such important PN-scaffolds, thus limiting their broad use. Here, we report a general and modular method for constructing these pseudo-natural N-bridged [3.3.1] ring systems via cascade process by bifunctional phosphonium salt/Lewis acid relay catalysis. A wide variety of substrates bearing an assortment of functional groups (59 examples) are compatible with this protocol. Other features include a [3 + 2] cyclization/ring-opening/Friedel-Crafts cascade pathway, excellent reactivities and stereoselectivities, easily available starting materials, step economy and scalability. The obtained enantioenriched products showed potential of preliminary anticancer activities. Insights gained from our studies are expected to advance general efforts towards the catalytic synthesis of challenging even unprecedented chiral PNPs, offering new opportunities for bioactive small-molecule discovery.

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confidence: 99%

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confidence: 99%

Asymmetric synthesis of N-bridged [3.3.1] ring systems by phosphonium salt/Lewis acid relay catalysis

Tan

Shen

et al. 2022

Nat Commun

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“…Trudell 145 had originally achieved a total synthesis of (±)-suaveoline from (±)-tryptophan and in 1992 Fu et al 146 finished a total synthesis of (−)-suaveoline via the asymmetric Pictet–Spengler reaction. In 2000 Bailey and Morgan developed a synthesis of (−)-suaveoline starting from L-tryptophan.…”

Section: Synthesismentioning

confidence: 99%

Sarpagine and Related Alkaloids

Namjoshi

Cook

2016

The Alkaloids: Chemistry and Biology

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The sarpagine-related macroline and ajmaline alkaloids share a common biosynthetic origin, and bear important structural similarities, as expected. These indole alkaloids are widely dispersed in 25 plant genera, principally in the Apocynaceae family. Very diverse and interesting biological properties have been reported for this group of natural products. Isolation of new sarpagine-related alkaloids as well as the asymmetric synthesis of these structurally complex molecules are of paramount importance to the synthetic and medicinal chemists. A total of 115 newly isolated sarpagine-related macroline and ajmaline alkaloids, along with their physicochemical properties have been included in this chapter. A general and efficient strategy for the synthesis of these monomeric alkaloids, as well as bisindoles has been presented, which involves application of the asymmetric Pictet–Spengler reaction (>98% ee) as a key step because of the ease of scale up of the tetracyclic template. Also included in this chapter are the syntheses of the sarpagine-related alkaloids, published since the year 2000.

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“…Indoline skeletons have been considered as characteristic structures owing to their widespread use as key building blocks and chiral auxiliaries in asymmetric synthesis [1]. They are also widely present in alkaloids and other natural products with diverse biological activities [2][3][4][5][6][7][8][9], such as pentopril, which is a potent angiotensin enzyme inhibitor [3], strychnine, which is used as a pesticide [2], and lundurine A, which is effective for overcoming multidrug resistance in vincristine-resistant KB cells ( Fig. 1) [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Co(III)/Zn(II)-catalyzed dearomatization of indoles and coupling with carbenes from ene-yne ketones via intramolecular cyclopropanation

Chang

Kong

et al. 2018

Chinese Journal of Catalysis

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Enantiospecific total synthesis of the ajmaline related alkaloids (-)-suaveoline, (-)-raumacline, and (-)-Nb-methylraumacline

Cited by 59 publications

References 7 publications

Asymmetric synthesis of N-bridged [3.3.1] ring systems by phosphonium salt/Lewis acid relay catalysis

Asymmetric synthesis of N-bridged [3.3.1] ring systems by phosphonium salt/Lewis acid relay catalysis

Sarpagine and Related Alkaloids

Co(III)/Zn(II)-catalyzed dearomatization of indoles and coupling with carbenes from ene-yne ketones via intramolecular cyclopropanation

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