Concise Enantiospecific, Stereoselective Syntheses of (+)-Crispine A and Its (−)-Antipode

Mahender, Gurram; Gyimóthy, Balázs; Wang, Ruifang; Lam, Sang Q.; Ahmed, Feryan; Herr, R. J.

doi:10.1021/jo102112k

Cited by 30 publications

(9 citation statements)

References 94 publications

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“…(–)‐( S )‐8,9‐Dimethoxy‐1,2,3,5,6,10b‐hexahydropyrrolo[2,1‐ a ]isoquinoline [(–)‐crispine] (1): Using the same procedure as above (for (+)‐ 1 ) compound ( – )‐ 1 was synthesized in 79 % yield. Spectroscopic data and optical rotation are in full agreement with reported in literature 12. [ α ] D 25 = –88 ( c = 1, CHCl 3 ).…”

Section: Methodssupporting

confidence: 87%

Asymmetric Synthesis of Crispine A: Constructing Tetrahydroisoquinoline Scaffolds Using Pummerer Cyclizations

2013

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For the first time, a concise, linear and stereoselective synthesis of both enantiomers of the natural product crispine A has been achieved in six steps with an overall yield of ≥ 20 %, starting from commercially available veratraldehyde. Asymmetric Keck allylation and trifluoroacetic anhydride‐mediated Pummerer cyclization were the key transformations used to construct the tetrahydroisoquinoline core structure.

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Section: Methodssupporting

confidence: 87%

Asymmetric Synthesis of Crispine A: Constructing Tetrahydroisoquinoline Scaffolds Using Pummerer Cyclizations

2013

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“…Our deprotonation–transmetalation–Negishi coupling process is also suitable for natural product synthesis, and the cytotoxic alkaloid ( R )-crispine A, isolated from Carduus Crispus , was selected as an appropriate target. In recent times, ( R )- or ( S )-crispine A has proved to be a popular target molecule, and several asymmetric strategies have been reported . The shortest route to ( R )-crispine A is 3 steps (32% overall yield) and is also the most recently reported synthesis .…”

Section: Resultsmentioning

confidence: 99%

Enantioselective, Palladium-Catalyzed α-Arylation of N-Boc Pyrrolidine: In Situ React IR Spectroscopic Monitoring, Scope, and Synthetic Applications

et al. 2011

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A comprehensive study of the enantioselective Pd-catalyzed α-arylation of N-Boc pyrrolidine has been carried out. The protocol involves deprotonation of N-Boc pyrrolidine using s-BuLi/(-)-sparteine in TBME or Et(2)O at -78 °C, transmetalation with ZnCl(2) and Negishi coupling using Pd(OAc)(2), t-Bu(3)P-HBF(4) and the aryl bromide. This paper reports several new features including in situ React IR spectroscopic monitoring of the process; use of (-)-sparteine and the (+)-sparteine surrogate to access products with opposite configuration; development of a catalytic asymmetric lithiation-Negishi coupling reaction; extension to a wide range of heteroaromatic bromides; total synthesis of (R)-crispine A, (S)-nicotine and (S)-SIB-1508Y via short synthetic routes; and examples of α-vinylation of N-Boc pyrrolidine using vinyl bromides exemplified by the total synthesis of naturally occurring (+)-maackiamine (thus establishing its configuration as (R)). In this way, the full scope and limitations of the methodology are delineated.

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“…Herr and co-workers, 64 using commercially available methyl esters of (S)-and (R)-3,4-dimethoxyphenylalanine (171 and ent-171) and 4-chloro-1,1-dimethoxybutane (172) as substrates, synthesized the natural (R)-crispine A (177), a pyrroloisoquinoline alkaloid, and its (S)-enantiomer (ent-177) using the Pictet− Spengler methodology. Scheme 17 shows the three-step synthesis of the natural and unnatural alkaloids.…”

Section: Pictet−spengler Cyclizationmentioning

confidence: 99%

Asymmetric Synthesis of Isoquinoline Alkaloids: 2004–2015

2016

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In the past decade, the asymmetric synthesis of chiral nonracemic isoquinoline alkaloids, a family of natural products showing a wide range of structural diversity and biological and pharmaceutical activity, has been based either on continuation or improvement of known traditional methods or on new, recently developed, strategies. Both diastereoselective and enantioselective catalytic methods have been applied. This review describes the stereochemically modified traditional syntheses (the Pictet-Spengler, the Bischler-Napieralski, and the Pomeranz-Fritsch-Bobbitt) along with strategies based on closing of the nitrogen-containing ring B of the isoquinoline core by the formation of bonds between C-N, N-C, C-N/N-C, and C-N/C-C atoms. Methods involving introduction of substituents at the C1 carbon of isoquinoline core along with syntheses applying various biocatalytic techniques have also been reviewed.

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Concise Enantiospecific, Stereoselective Syntheses of (+)-Crispine A and Its (−)-Antipode

Cited by 30 publications

References 94 publications

Asymmetric Synthesis of Crispine A: Constructing Tetrahydroisoquinoline Scaffolds Using Pummerer Cyclizations

Asymmetric Synthesis of Crispine A: Constructing Tetrahydroisoquinoline Scaffolds Using Pummerer Cyclizations

Enantioselective, Palladium-Catalyzed α-Arylation of N-Boc Pyrrolidine: In Situ React IR Spectroscopic Monitoring, Scope, and Synthetic Applications

Asymmetric Synthesis of Isoquinoline Alkaloids: 2004–2015

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