Radical Cyclization of <i>N</i>‐Acylcyanamides: Total Synthesis of Luotonin A

Servais, Aurore; Azzouz, Mériam; Lopes, David; Courillon, Christine; Malacrìa, Max

doi:10.1002/anie.200602940

Cited by 142 publications

(57 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As an extension of the known radical additions to isonitriles [87], aryl radical cyclizations to N-acyl cyanamides provide new access to pyrrolo-quinazolines (Scheme 16) [88]. In a tandem process, the iminyl radical 41 resulting from the 5-exo cyclization onto the nitrile was used for a second cyclization step.…”

Section: Applications In Natural Product Synthesismentioning

confidence: 99%

Modern Developments in Aryl Radical Chemistry

Pratsch

Heinrich

2011

Topics in Current Chemistry

View full text Add to dashboard Cite

This review summarizes recent advances in the field of aryl radical chemistry. In particular, modern developments of the well-known Meerwein, Pschorr, and Gomberg-Bachmann reactions are presented along with new applications in natural product syntheses. Among the methods for the generation of aryl radicals, tin hydrides play a predominant role, but more and more attractive and promising alternatives are beginning to emerge.

show abstract

Section: Applications In Natural Product Synthesismentioning

confidence: 99%

Modern Developments in Aryl Radical Chemistry

Pratsch

Heinrich

2011

Topics in Current Chemistry

View full text Add to dashboard Cite

show abstract

“…Courillon and coworkers reported a cascade radical cyclization of N -acylcyanamides as an alternative procedure for the 4(3 H )-quinazolinone nucleus, which led to the total synthesis of luotonin A [46,47] (Scheme 15). Cyanation of N -[(2-iodoquinol-3-yl)methyl]benzamide with cyanogen bromide afforded the corresponding N -CN compound which was subjected to radical cyclization to yield luotonin A.…”

Section: Synthesismentioning

confidence: 99%

Recent Advances in the Studies on Luotonins

2011

View full text Add to dashboard Cite

Luotonins are alkaloids from the aerial parts of Peganum nigellastrum Bunge. that display three major skeleton types. Luotonins A, B, and E are pyrroloquinazolino-quinoline alkaloids, luotonins C and D are canthin-6-one alkaloids, and luotonin F is a 4(3H)-quinazolinone alkaloid. All six luotonins have shown promising cytotoxicities towards selected human cancer cell lines, especially against leukemia P-388 cells. Luotonin A is the most active one, with its activity stemming from topoisomerase I-dependent DNA-cleavage. Such intriguing biological activities and unique structures have led not only to the development of synthetic methods for the efficient synthesis of these compounds, but also to interest in structural modifications for improving the biological properties. Recent progress in the study of luotonins is covered.

show abstract

“…[38][39][40][41][42][43] As a part of our research on biologically important natural products, we herein described a simple one-pot procedure for the preparation of 1 as well as related alkaloids 3, 4 and 5 in multi-gram quantity.…”

Section: )mentioning

confidence: 99%

“…10,12) Nevertheless, the biological importance of 4(3H)-quinazolinone and related compounds still spurred the development of a new and simple synthetic method for theses compounds. [38][39][40][41][42][43] As a part of our research on biologically important natural products, we herein described a simple one-pot procedure for the preparation of 1 as well as related alkaloids 3, 4 and 5 in multi-gram quantity.…”

mentioning

confidence: 99%

One-Pot Synthesis of Simple Alkaloids: 2,3-Polymethylene-4(3<i>H</i>)-quinazolinones, Luotonin A, Tryptanthrin, and Rutaecarpine

Jahng

Kim

et al. 2008

Chem. Pharm. Bull.

View full text Add to dashboard Cite

2,3-Trimethylene-4(3H)-quinazolinone (deoxyvasicinone, 1aa) 1) and 2,3-tetramethylene-4(3H)-quinazolinone (mackinazolinone, 1ba) 2,3) are not only the alkaloids isolated from Peganum and Mackinlaya species, respectively, but are also prepared chemically before the isolation from natural sources. [4][5][6] The establishment of a simple and efficient synthetic method for these alkaloids has long been a challenging subject. [7][8][9][10][11][12][13][14][15][16][17][18][19][20] In addition, these substances are a part of the family of intriguing alkaloids that include the bronchodilator vasicinone (2a) from Adhatoda vasica, 21) antiendotoxic isaindigotone (2b) from Isatis indigotica, 22) topoisomerase Idependent cytotoxic luotonin A (3) from Peganum nigellastrum, 23) antibiotic tryptanthrin (4) from yeast (Candida lipolytica) 24,25) and later from cannon ball tree (Cououpita guianensis), 26) anti-inflammatory rutaecarpine (5) 27) from Evodia rutaecarpa, and related alkaloids (Fig. 1). 28)Since Niementowski's preparation of 4(3H)-quinazolinone by fusing anthranilic acid with formamide, 29) several methods attempting the synthesis of modified quinazolinones have been reported. 1,[30][31][32][33] Although most of these are applicable to acyclic amides, methods for cyclic amides, especially without an aryl group, are somewhat limited. [34][35][36][37] These limitations have led to the continuous development of new procedures for cyclic amides, such as cyclocondensation of isatoic anhydride with lactams, 12) metal catalyzed reductive N-heterocyclization of N-(2-nitrobenzoyl)lactams in the presence of CO,13,14) reaction of 2-aminobenzamide with succinic anhydride, 15) intramolecular aza-Wittig reaction of N-(2-azidobenzoyl)lactams, 9,16) condensation of anthranilic acid with O-alkyllactims 6,[18][19][20] or S-alkyllactims, 8) reaction of anthranilic acid with SOCl 2 followed by cyclization with lactams, 17) cyclization of iminochlorides generated from lactam and methyl anthranilate, 11) solid-phase synthesis, 7,9) and microwave assisted synthesis.10,12) Nevertheless, the biological importance of 4(3H)-quinazolinone and related compounds still spurred the development of a new and simple synthetic method for theses compounds. [38][39][40][41][42][43] As a part of our research on biologically important natural products, we herein described a simple one-pot procedure for the preparation of 1 as well as related alkaloids 3, 4 and 5 in multi-gram quantity.Although an earlier study revealed that iminoketene (8), generated from the reaction of anthranilic acid (6) and SOCl 2 , underwent cycloaddition to cyclic iminols, which are tautomers of the corresponding lactams (9), to yield 1 in 70-82% yield, 19) we sometimes have been unable to repeat the reactions.44) Whenever we failed to generate the desired products, imine compounds (10) were isolated as major products (Chart 1). Although we could convert these imines (10) to the desired 2,3-tri-and 2,3-tetramethylene-4(3H)-quinazolinones by employing polyphosphoric acid-catalyzed deh...

show abstract

Radical Cyclization of N‐Acylcyanamides: Total Synthesis of Luotonin A

Cited by 142 publications

References 61 publications

Modern Developments in Aryl Radical Chemistry

Modern Developments in Aryl Radical Chemistry

Recent Advances in the Studies on Luotonins

One-Pot Synthesis of Simple Alkaloids: 2,3-Polymethylene-4(3<i>H</i>)-quinazolinones, Luotonin A, Tryptanthrin, and Rutaecarpine

Contact Info

Product

Resources

About