Reaktionen an Indolderivaten, XXV. Die stereoselektive Totalsynthese des Roxburghins D

Benz, G.; Riesner, Hubert; Winterfeldt, Ekkehard

doi:10.1002/cber.19751080132

Cited by 17 publications

(10 citation statements)

References 8 publications

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“…Acid-promoted lactam equilibration can take place under special circumstances, such as when a 3-indolyl group is involved. − Lactam 23b , the exclusive isomer from N -acyliminium cyclization of keto amide 22 (eq 10), is separately converted to epimer 23a on treatment with trifluoroacetic acid . However, this equilibration requires harsher acidic conditions (CF 3 CO 2 H, >15 h, room temperature) than the cyclization of 22 (1% aqueous CF 3 CO 2 H, room temperature) . This process can proceed with even greater facility, such as with lactams 24a and 24b , which independently equilibrate to a 70:30 mixture with trifluoroacetic acid in 2 h at room temperature, or in 5 min at reflux .…”

Section: 2 Kinetic and Thermodynamic Controlmentioning

confidence: 99%

“…These inauspicious results could be associated with several factors: (1) an absence of steric distinction between substituents on a key stereogenic center, (2) location of the stereogenic center relative to the newly formed bond(s), (3) equilibration of product diastereomers, − , or (4) excessive conformational flexibility. For example, a single stereogenic center adjacent (α) to the carbocation center that is generated is not conducive to good stereocontrol (e.g., eq 15 93 ), ,,,− although certain structural constraints can alter this situation (eq 10) . In some cases a β stereogenic center fosters good stereocontrol (e.g., eq 16 105 ), − whereas in others it does not (e.g., eq 17 103 ). , Nevertheless, highly stereoselective N -acyliminium cyclizations are integral steps in the syntheses of inter alia roxburghin D, eburnamonine, quebrachamine, antirhines, , vindorosine, vindoline, 20-desethylvincadifformine, and geissoschizine …”

Section: 31 Benzenoid and Heterocyclic Nucleophilesmentioning

confidence: 99%

“…For example, a single stereogenic center adjacent (α) to the carbocation center that is generated is not conducive to good stereocontrol (e.g., eq 15 93 ), ,,,− although certain structural constraints can alter this situation (eq 10) . In some cases a β stereogenic center fosters good stereocontrol (e.g., eq 16 105 ), − whereas in others it does not (e.g., eq 17 103 ). , Nevertheless, highly stereoselective N -acyliminium cyclizations are integral steps in the syntheses of inter alia roxburghin D, eburnamonine, quebrachamine, antirhines, , vindorosine, vindoline, 20-desethylvincadifformine, and geissoschizine

…”

Section: 31 Benzenoid and Heterocyclic Nucleophilesmentioning

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: 2 Kinetic and Thermodynamic Controlmentioning

confidence: 99%

Section: 31 Benzenoid and Heterocyclic Nucleophilesmentioning

confidence: 99%

…”

Section: 31 Benzenoid and Heterocyclic Nucleophilesmentioning

confidence: 99%

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Cyclizations of N-Acyliminium Ions

et al. 2004

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“…[2] Substituted N-acyliminium ions E, with stereocenters contained within the structure, can be generated from a wide variety of precursors, [2] and in recent years, elegant organocatalyzed processes have been devel-A few examples of the acid-promoted epimerization of the stereocenter of nitrogen heterocycle F, which resulted from a Pictet-Spengler cyclization of an indole and an Nacyliminium ion, have been reported. [8] Additionally, diastereodivergent Pictet-Spengler reactions that control the resulting tertiary stereocenter and involve electron-rich π-nucleophiles, such as indoles, furans, and 3,5-dimethoxyphenyl groups, have also been observed to depend on the reaction conditions (kinetic vs. thermodynamic control). [7] Recently, we reported a new access to bicyclic enamides I, which contain a 4-methylene-3-azabicyclo[3.1.0]-hexan-2-one core, by employing a two-step procedure that started from cis-2-iodocyclopropanecarboxamides G, derived from homoveratrylamine.…”

Section: Introductionmentioning

confidence: 98%

“…[1,2] The control of the configuration of the new stereocenter that is formed during the course of a Pictet-Spengler cyclization has been the focus of numerous investigations. [1][2][3][4][5][6][7][8] In the last decade, these research efforts have culminated in the development of catalytic enantioselective reactions by using chiral thioureas [3] or Brønsted acids, [4] but the control of the newly formed asymmetric carbon often relies on diastereoselective reactions. [1,2] One of the classical versions of the PictetSpengler reaction arguably involves the condensation of Nsubstituted tryptophan ester A with an aldehyde in the presence of an acid catalyst.…”

Section: Introductionmentioning

confidence: 99%

Diastereodivergent Pictet–Spengler Cyclization of Bicyclic N‐Acyliminium Ions: Controlling a Quaternary Stereocenter

Carné-Carnavalet

Krieger

Folléas³

et al. 2015

Eur J Org Chem

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The diastereoselectivity of the Pictet–Spengler cyclization of bicyclic N‐acyliminium ions that contain a 3‐azabicyclo[n.3.0]alkane core and an electron‐rich π‐nucleophilic moiety, such as an indol‐2‐yl, indol‐3‐yl, 1‐methylpyrrol‐2‐yl, or 3,5‐dimethoxyphenyl group, was examined. The N‐acyliminium ions were generated by protonation of the corresponding enamides or hemiaminals, which were derived from imides. Control of the quaternary stereocenter created at the newly formed ring junction was achieved in a diastereodivergent manner by fine‐tuning the reaction conditions, which determined whether the reaction proceeded under kinetic or thermodynamic control. Mechanistic studies indicated that a retro‐Pictet–Spengler reaction pathway is involved in the equilibration process.

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Synthetic and Natural Sources of the Isoquinoline Nucleus

Kametani

Fukumoto

1981

Chemistry of Heterocyclic Compounds: A Series of Monographs

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Reaktionen an Indolderivaten, XXV. Die stereoselektive Totalsynthese des Roxburghins D

Cited by 17 publications

References 8 publications

Cyclizations of N-Acyliminium Ions

Cyclizations of N-Acyliminium Ions

Diastereodivergent Pictet–Spengler Cyclization of Bicyclic N‐Acyliminium Ions: Controlling a Quaternary Stereocenter

Synthetic and Natural Sources of the Isoquinoline Nucleus

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