A total synthesis of chelidonine

Cushman, Mary; Choong, Tung-Chung; Valko, Joseph T.; Koleck, Mary P.

doi:10.1016/0040-4039(80)80196-1

Cited by 24 publications

(8 citation statements)

References 20 publications

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“…Imines can combine with cyclic anhydrides to yield cyclocondensation products that appear to arise from addition of a carboxylic acid enolate to an intermediate N -acyliminium species (e.g., eq 58). ,− A prototypical reaction involving succinic anhydride and PhCHNMe yields pyrrolidinone 210 as a mixture enriched in the trans isomer (eq 58) . Generally, succinic, glutaric, and homophthalic anhydrides condense well with benzaldimines, but just moderate stereochemical control is obtained.…”

Section: 34 Carbonyl Groups As Nucleophiles Via Enols and Enolatesmentioning

confidence: 99%

“…An enolate-based N -acyliminium cyclization that is useful in the synthesis of isoquinoline alkaloids involves the condensation of imines and cyclic anhydrides. ,− This approach is illustrated by the reaction of succinic anhydride with PhCHNMe in eq 58 . The reaction transpires well with succinic, glutaric, or homophthalic anhydrides and with benzaldimines.…”

Section: 46 Enols and Enolatesmentioning

confidence: 99%

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Cyclizations of N-Acyliminium Ions

et al. 2004

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effectively in cyclizations with N-acyliminum species. Electron-attracting substituents other than N-acyl, such as N-sulfonyl, can also be employed in analogues of N-acyliminium ion reactions. However, this review will concentrate on cyclizations of the N-acyl type, encompassing groups such as alkanoyl, aroyl, carbalkoxy, and N,N-dialkylcarbamyl, with limited coverage of sulfonyl groups. Most significantly, this review will focus on intramolecular reactions of N-acyliminium ions that result in the formation of new carbon-carbon bonds, rather than new carbonheteroatom bonds. Although β-lactam synthesis based on the cyclocondensation of imines with acid halides, Bruce E. Maryanoff earned B.S. (1969) and Ph.D. (1972) degrees from Drexel University and then conducted postdoctoral studies at Princeton University, working with Prof. Kurt Mislow. He joined McNeil Laboratories, a Johnson & Johnson subsidiary, in 1974 and advanced to Distinguished Research Fellow, the highest scientific position in the company. From 1976 to 1992, he principally worked on discovering drugs for treating central nervous system disorders; in 1992, he moved into cardiovascular research and presently leads the Vascular Research Team. Dr. Maryanoff is recognized for his work in organic and medicinal chemistry, especially the Wittig olefination reaction; peptides and peptidomimetics; antiepileptics and antidepressants; thrombin inhibitors; and protease-activated receptors. He discovered TOPAMAX topiramate, which is marketed worldwide for the treatment of epilepsy and is being developed for migraine headache. He has published 200 scientific papers, is an inventor on 60 U.S. patents, and has received two national awards, the ACS Heroes of Chemistry Award (2000) and the ACS Award in Industrial Chemistry (2003). Dr. Maryanoff is a Fellow in the American Association for the Advancement of Science and the Royal Society of Chemistry. Han-Cheng Zhang received B.S. and M.S. degrees in chemistry from Xiamen University, P.R.C., and served as a faculty member there for 5 years. He came to the United States and earned a Ph.D. degree in organic chemistry from Rensselaer Polytechnic Institute (1992), working with Prof. Doyle Daves. He joined the R. W. Johnson Pharmaceutical Research Institute as a Postdoctoral Scientist with Dr. Bruce Maryanoff and, after one year, as a Scientist. Dr. Zhang has worked as a medicinal chemist in the areas of G-protein-coupled receptors, proteases, and kinases to discover new drug candidates, recently leading a project that identified the first potent, selective antagonists for the thrombin receptor, proteaseactivated receptor 1. He is now at the level of Principal Scientist in Johnson & Johnson Pharmaceutical Research & Development. Dr. Zhang has published over 40 scientific papers and is an inventor on 13 U.S. patents (issued or pending). His scientific interests include the design and synthesis of novel therapeutic agents, heterocycles, stereoselective reactions, organometallic chemistry, and solid-phase organic synthesis. Judi...

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Section: 34 Carbonyl Groups As Nucleophiles Via Enols and Enolatesmentioning

confidence: 99%

Section: 46 Enols and Enolatesmentioning

confidence: 99%

Cyclizations of N-Acyliminium Ions

et al. 2004

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“…Limited efforts towards the syntheses of B/C hexahydrobenzo[c]phenanthridine alkaloids have been reported. These include racemic syntheses of homochelidonine, [13] chelamidine, [13c] chelidonine, [14] chelamine [14e] and norchelidonine. [14a, d] Abstract: New enantioselective syntheses of the B/C hexahydrobenzo[c]phenanthridine alkaloids (+)-homochelidonine, (+)-chelamidine, (+)-chelidonine, (+)-chelamine, and (+)-norchelidonine are described.…”

Section: Introductionmentioning

confidence: 99%

Concise Enantioselective Total Syntheses of (+)‐Homochelidonine, (+)‐Chelamidine, (+)‐Chelidonine, (+)‐Chelamine and (+)‐Norchelidonine by a Pd^II‐Catalyzed Ring‐Opening Strategy

Fleming

McManus

Rudolph

et al. 2008

Chemistry A European J

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New enantioselective syntheses of the B/C hexahydrobenzo[c]phenanthridine alkaloids (+)-homochelidonine, (+)-chelamidine, (+)-chelidonine, (+)-chelamine, and (+)-norchelidonine are described. Our rapid and convergent route to this class of natural products involved the development and application of a Pd II-catalyzed asymmetric ring-opening reaction of a meso-azabicyclic alkene with an aryl boronic acid as the key step. By screening a variety of functionalized ortho-substituted aryl boronic acids, chiral ligands and reaction conditions we were able to prepare the requisite cis-1-amino-2-aryldihydronaphthalenes in high yield and in up to 90 % ee. Early attempts to complete the synthesis of (+)-homochelidonine using an N-Boc azabicyclic alkene are described in full. The successful route required a protecting group alteration followed by B ring formation and then stereoselective installation of the C-11 syn-hydroxy group by regioselective epoxide ring-opening using a hydride source. Ring-opening of the same epoxide intermediate with water ultimately led to the synthesis of (+)-chelamidine. The same strategy was then used to synthesize the other structurally similar B/C hexahydrobenzo[c]phenanthridine alkaloids, (+)-chelidonine, (+)-chelamidine, and (+)-norchelidonine.

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“…It was isolated from C. majus (Papaveraceae) as early as 1839, while it could be synthesized from 1971 onwards, and biosynthesis from dopamine was first reported in 1979 (summarized in Cushman et al 1980;Hanakoa et al 1986;Schmahl and Mehlhorn 1985). Chelidonine was shown to cause mitotic arrest by Lettre and Albrecht (1942) and has recently been shown to inhibit tubulin polymerization (Wolff and Knipling 1993).…”

Section: Resultsmentioning

confidence: 98%

In vivo anthelmintic activity of chelidonine from Chelidonium majus L. against Dactylogyrus intermedius in Carassius auratus

Yao

Zhang

et al. 2011

Parasitol Res

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Dactylogyrus intermedius is one of the most common and serious cause of parasitic diseases of freshwater fish in aquaculture, and can cause morbidity and high mortality in most species of freshwater fish worldwide. To attempt controlling this parasite and explore novel potential antiparasitic agents, the present study was designed to ascertain the anthelmintic activity of Chelidonium majus L. whole plant and to isolate and characterize the active constituents against D. intermedius. The ethanol extract from C. majus whole plant showed significant anthelmintic activity against D. intermedius [EC(50) (median effective concentration) value = 71.5 mg L(-1)] and therefore subjected to further isolation and purification using various chromatographic techniques. A quaternary benzo[c]phenanthridine alkaloid exhibited significant activity against D. intermedius was obtained and identified as chelidonine. In vivo anthelmintic efficacy tests exhibited that chelidonine was 100% effective against D. intermedius at a concentration of 0.9 mg L(-1), with EC(50) value of 0.48 mg L(-1) after 48 h of exposure, which is more effective than the positive control, mebendazole (EC(50) value = 1.3 mg L(-1)). In addition, the 48-h median lethal concentration (LC(50)) for chelidonine against the host (Carassius auratus) was 4.54 mg L(-1). The resulting therapeutic index for chelidonine was 9.46. These results provided evidence that chelidonine might be potential sources of new antiparasitic drugs for the control of Dactylogyrus.

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A total synthesis of chelidonine

Cited by 24 publications

References 20 publications

Cyclizations of N-Acyliminium Ions

Cyclizations of N-Acyliminium Ions

Concise Enantioselective Total Syntheses of (+)‐Homochelidonine, (+)‐Chelamidine, (+)‐Chelidonine, (+)‐Chelamine and (+)‐Norchelidonine by a Pd^II‐Catalyzed Ring‐Opening Strategy

In vivo anthelmintic activity of chelidonine from Chelidonium majus L. against Dactylogyrus intermedius in Carassius auratus

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A total synthesis of chelidonine

Cited by 24 publications

References 20 publications

Cyclizations of N-Acyliminium Ions

Cyclizations of N-Acyliminium Ions

Concise Enantioselective Total Syntheses of (+)‐Homochelidonine, (+)‐Chelamidine, (+)‐Chelidonine, (+)‐Chelamine and (+)‐Norchelidonine by a PdII‐Catalyzed Ring‐Opening Strategy

In vivo anthelmintic activity of chelidonine from Chelidonium majus L. against Dactylogyrus intermedius in Carassius auratus

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Concise Enantioselective Total Syntheses of (+)‐Homochelidonine, (+)‐Chelamidine, (+)‐Chelidonine, (+)‐Chelamine and (+)‐Norchelidonine by a Pd^II‐Catalyzed Ring‐Opening Strategy