The synthesis of pyrrolo[1,2-b][1,2,5]benzothiadiazepines from 1,2-thiazine 1-oxides - Sulfonamide analogues of the pyrrolobenzodiazepine antitumour natural products

Karl Hemming, Nilesh Patel

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19 Citations (Scopus)

Abstract

Pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) and the corresponding pyrrolobenzothiadiazepines (PBTDs) are attractive targets as natural and synthetic antitumour antibiotics and as non-nucleosidic reverse transcriptase inhibitors. A concise synthesis of the PBTD class is presented, which starts from o-azidobenzenesulfonamide and its conversion into 2-(o- azidobenzenesulfonyl)-1,2-thiazine 1-oxides via Diels-Alder reaction. After a one-pot ring contraction, desulfurisation and aromatisation process, accompanied by concomitant same pot conversion of the azide group into a primary amine via the Staudinger reaction, these 1,2-thiazine-1-oxides yield a 1-(o-aminobenzenesulfonyl)pyrrole. N-Formylation of the amine and Bischler-Napieralski ring closure onto the pyrrole completes the PBTD synthesis.

Original languageEnglish
Pages (from-to)7553-7556
Number of pages4
JournalTetrahedron Letters
Volume45
Issue number41
Early online date11 Sep 2004
DOIs
Publication statusPublished - 4 Oct 2004

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Thiazines
Pyrroles
Sulfonamides
Biological Products
Oxides
Amines
Aromatization
Reverse Transcriptase Inhibitors
Azides
Cycloaddition Reaction
Anti-Bacterial Agents
pyrrolo(2,1-c)(1,4)benzodiazepine

Cite this

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title = "The synthesis of pyrrolo[1,2-b][1,2,5]benzothiadiazepines from 1,2-thiazine 1-oxides - Sulfonamide analogues of the pyrrolobenzodiazepine antitumour natural products",
abstract = "Pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) and the corresponding pyrrolobenzothiadiazepines (PBTDs) are attractive targets as natural and synthetic antitumour antibiotics and as non-nucleosidic reverse transcriptase inhibitors. A concise synthesis of the PBTD class is presented, which starts from o-azidobenzenesulfonamide and its conversion into 2-(o- azidobenzenesulfonyl)-1,2-thiazine 1-oxides via Diels-Alder reaction. After a one-pot ring contraction, desulfurisation and aromatisation process, accompanied by concomitant same pot conversion of the azide group into a primary amine via the Staudinger reaction, these 1,2-thiazine-1-oxides yield a 1-(o-aminobenzenesulfonyl)pyrrole. N-Formylation of the amine and Bischler-Napieralski ring closure onto the pyrrole completes the PBTD synthesis.",
keywords = "1,2-Thiazine-1-oxide, Azide, Pyrrole, Pyrrolobenzodiazepine, Pyrrolobenzothiadiazepine",
author = "Karl Hemming and Nilesh Patel",
year = "2004",
month = "10",
day = "4",
doi = "10.1016/j.tetlet.2004.08.136",
language = "English",
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pages = "7553--7556",
journal = "Tetrahedron Letters",
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TY - JOUR

T1 - The synthesis of pyrrolo[1,2-b][1,2,5]benzothiadiazepines from 1,2-thiazine 1-oxides - Sulfonamide analogues of the pyrrolobenzodiazepine antitumour natural products

AU - Hemming, Karl

AU - Patel, Nilesh

PY - 2004/10/4

Y1 - 2004/10/4

N2 - Pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) and the corresponding pyrrolobenzothiadiazepines (PBTDs) are attractive targets as natural and synthetic antitumour antibiotics and as non-nucleosidic reverse transcriptase inhibitors. A concise synthesis of the PBTD class is presented, which starts from o-azidobenzenesulfonamide and its conversion into 2-(o- azidobenzenesulfonyl)-1,2-thiazine 1-oxides via Diels-Alder reaction. After a one-pot ring contraction, desulfurisation and aromatisation process, accompanied by concomitant same pot conversion of the azide group into a primary amine via the Staudinger reaction, these 1,2-thiazine-1-oxides yield a 1-(o-aminobenzenesulfonyl)pyrrole. N-Formylation of the amine and Bischler-Napieralski ring closure onto the pyrrole completes the PBTD synthesis.

AB - Pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) and the corresponding pyrrolobenzothiadiazepines (PBTDs) are attractive targets as natural and synthetic antitumour antibiotics and as non-nucleosidic reverse transcriptase inhibitors. A concise synthesis of the PBTD class is presented, which starts from o-azidobenzenesulfonamide and its conversion into 2-(o- azidobenzenesulfonyl)-1,2-thiazine 1-oxides via Diels-Alder reaction. After a one-pot ring contraction, desulfurisation and aromatisation process, accompanied by concomitant same pot conversion of the azide group into a primary amine via the Staudinger reaction, these 1,2-thiazine-1-oxides yield a 1-(o-aminobenzenesulfonyl)pyrrole. N-Formylation of the amine and Bischler-Napieralski ring closure onto the pyrrole completes the PBTD synthesis.

KW - 1,2-Thiazine-1-oxide

KW - Azide

KW - Pyrrole

KW - Pyrrolobenzodiazepine

KW - Pyrrolobenzothiadiazepine

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U2 - 10.1016/j.tetlet.2004.08.136

DO - 10.1016/j.tetlet.2004.08.136

M3 - Article

VL - 45

SP - 7553

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JO - Tetrahedron Letters

JF - Tetrahedron Letters

SN - 0040-4039

IS - 41

ER -