The synthesis of naturally occurring quinones
The synthesis of naturally occurring quinones
Mi.mosamycin, saframycins A,B,C,D,E and S, mimocin, renierone and naphthyridinomycin are naturally occurring quinones, characterised by the presence of a 7-methoxy-6-methyl-5,8-isoquinolinedione or related structural unit. They exhibit antibiotic and in some cases antitumour activity. In Chapter One an approach to the synthesis of mimocin and renierone is described. 5,7-Dimethoxy-6-methylisoquinoline, preparedby the Pomeranz-Fritsch reaction, was converted to 8-amino-5,7-dimethoxy6-methylisoquinoline. On treatment with ceric ammonium nitrate this gave 7-methoxy-6-methyl-5,8-isoquinolinedione and 5-methoxy-6-methyl7,8-isoquinolinedione. The two isomeric quinones were distinguished by comparison of their u.v., i.r., 'H and 13C n.m.r. and mass spectra. The former quinone was obtained by treatment of 5,7-dimethoxy-6methylisoquinoline with boron tribromide and oxidation of the product with Fremy's salt. It has been converted to mimocin by Japanese workers and it is believed that it may also be converted to renierone. The preparation of 2,5-dihydroxy-4-methoxy-3-methylbenzaldehyde, which might he used in the synthesis of mimocin, renierone and the saframycins is described. The anthracycline antibiotics daunomycin and adriamycin are widely used for the treatment of cancer. In Chapter Two a brief account of the biosynthesis, mode of action and structure-activity relationships of adriamycin and related anthracycline antibiotics is given. The strategies employed in previous approaches to the synthesis of adriamycin and related compounds are also reviewed. In Chapter Three an approach to the synthesis of daunomycinone and adriamycinone is described. It was envisaged that reaction of a phthalide anion with the Diels-Alder adduct of a 1,4-benzoquinone and a 1,3-butadiene would afford a tetracyclic intermediate, via conjugate addition of the anion followed by opening of the lactone ring by the resultant enolate, which could be elaborated to an anthracyclinone. In fact the phthalide anion behaved as a base and abstracted a proton from the Diels-Alder adduct which rendered this approach unsuccessful.
University of Southampton
Latham, Christopher John
8f9faaaf-08ba-42c3-b2f3-1e2af218e580
1981
Latham, Christopher John
8f9faaaf-08ba-42c3-b2f3-1e2af218e580
Latham, Christopher John
(1981)
The synthesis of naturally occurring quinones.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
Mi.mosamycin, saframycins A,B,C,D,E and S, mimocin, renierone and naphthyridinomycin are naturally occurring quinones, characterised by the presence of a 7-methoxy-6-methyl-5,8-isoquinolinedione or related structural unit. They exhibit antibiotic and in some cases antitumour activity. In Chapter One an approach to the synthesis of mimocin and renierone is described. 5,7-Dimethoxy-6-methylisoquinoline, preparedby the Pomeranz-Fritsch reaction, was converted to 8-amino-5,7-dimethoxy6-methylisoquinoline. On treatment with ceric ammonium nitrate this gave 7-methoxy-6-methyl-5,8-isoquinolinedione and 5-methoxy-6-methyl7,8-isoquinolinedione. The two isomeric quinones were distinguished by comparison of their u.v., i.r., 'H and 13C n.m.r. and mass spectra. The former quinone was obtained by treatment of 5,7-dimethoxy-6methylisoquinoline with boron tribromide and oxidation of the product with Fremy's salt. It has been converted to mimocin by Japanese workers and it is believed that it may also be converted to renierone. The preparation of 2,5-dihydroxy-4-methoxy-3-methylbenzaldehyde, which might he used in the synthesis of mimocin, renierone and the saframycins is described. The anthracycline antibiotics daunomycin and adriamycin are widely used for the treatment of cancer. In Chapter Two a brief account of the biosynthesis, mode of action and structure-activity relationships of adriamycin and related anthracycline antibiotics is given. The strategies employed in previous approaches to the synthesis of adriamycin and related compounds are also reviewed. In Chapter Three an approach to the synthesis of daunomycinone and adriamycinone is described. It was envisaged that reaction of a phthalide anion with the Diels-Alder adduct of a 1,4-benzoquinone and a 1,3-butadiene would afford a tetracyclic intermediate, via conjugate addition of the anion followed by opening of the lactone ring by the resultant enolate, which could be elaborated to an anthracyclinone. In fact the phthalide anion behaved as a base and abstracted a proton from the Diels-Alder adduct which rendered this approach unsuccessful.
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Published date: 1981
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Local EPrints ID: 459684
URI: http://eprints.soton.ac.uk/id/eprint/459684
PURE UUID: 8b58f81f-a37c-49c5-ac12-1a27aa38b4d9
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Date deposited: 04 Jul 2022 17:16
Last modified: 23 Jul 2022 00:31
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Author:
Christopher John Latham
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