Synthesis of simple analogues of methyllycaconitine - An efficient method for the preparation of the N-substituted anthranilate pharmacophore

David Barker; Margaret A. Brimble; Malcolm D. McLeod

doi:10.1016/j.tet.2004.05.024

Synthesis of simple analogues of methyllycaconitine - An efficient method for the preparation of the N-substituted anthranilate pharmacophore

David Barker, Margaret A. Brimble^*, Malcolm D. McLeod

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

23 Citations (Scopus)

Abstract

The synthesis of several A and AE ring analogues of the alkaloid methyllycaconitine is reported. The key 2-(2″-methylsuccinimido)benzoate ester pharmacophore is introduced using an efficient two step procedure. Esterification of the alcohol precursors with N-(trifluoroacetyl)anthranilic acid under Steglich conditions followed by sodium borohydride mediated cleavage of the trifluoroacetyl group affords the anthranilate esters. Subsequent fusion with methylsuccinic anhydride affords the N-substituted anthranilate derivatives containing the key pharmacophore present in a range of commonly occurring Delphinium and Aconitum alkaloids.

Original language	English
Pages (from-to)	5953-5963
Number of pages	11
Journal	Tetrahedron
Volume	60
Issue number	28
DOIs	https://doi.org/10.1016/j.tet.2004.05.024
Publication status	Published - 5 Jul 2004
Externally published	Yes

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10.1016/j.tet.2004.05.024

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title = "Synthesis of simple analogues of methyllycaconitine - An efficient method for the preparation of the N-substituted anthranilate pharmacophore",

abstract = "The synthesis of several A and AE ring analogues of the alkaloid methyllycaconitine is reported. The key 2-(2″-methylsuccinimido)benzoate ester pharmacophore is introduced using an efficient two step procedure. Esterification of the alcohol precursors with N-(trifluoroacetyl)anthranilic acid under Steglich conditions followed by sodium borohydride mediated cleavage of the trifluoroacetyl group affords the anthranilate esters. Subsequent fusion with methylsuccinic anhydride affords the N-substituted anthranilate derivatives containing the key pharmacophore present in a range of commonly occurring Delphinium and Aconitum alkaloids.",

keywords = "Alkaloids, Anthranilate esters, Methyllycaconitine, Nicotinic acetylcholine receptors",

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T1 - Synthesis of simple analogues of methyllycaconitine - An efficient method for the preparation of the N-substituted anthranilate pharmacophore

AU - Barker, David

AU - Brimble, Margaret A.

AU - McLeod, Malcolm D.

PY - 2004/7/5

Y1 - 2004/7/5

N2 - The synthesis of several A and AE ring analogues of the alkaloid methyllycaconitine is reported. The key 2-(2″-methylsuccinimido)benzoate ester pharmacophore is introduced using an efficient two step procedure. Esterification of the alcohol precursors with N-(trifluoroacetyl)anthranilic acid under Steglich conditions followed by sodium borohydride mediated cleavage of the trifluoroacetyl group affords the anthranilate esters. Subsequent fusion with methylsuccinic anhydride affords the N-substituted anthranilate derivatives containing the key pharmacophore present in a range of commonly occurring Delphinium and Aconitum alkaloids.

AB - The synthesis of several A and AE ring analogues of the alkaloid methyllycaconitine is reported. The key 2-(2″-methylsuccinimido)benzoate ester pharmacophore is introduced using an efficient two step procedure. Esterification of the alcohol precursors with N-(trifluoroacetyl)anthranilic acid under Steglich conditions followed by sodium borohydride mediated cleavage of the trifluoroacetyl group affords the anthranilate esters. Subsequent fusion with methylsuccinic anhydride affords the N-substituted anthranilate derivatives containing the key pharmacophore present in a range of commonly occurring Delphinium and Aconitum alkaloids.

KW - Alkaloids

KW - Anthranilate esters

KW - Methyllycaconitine

KW - Nicotinic acetylcholine receptors

UR - http://www.scopus.com/inward/record.url?scp=2942750323&partnerID=8YFLogxK

U2 - 10.1016/j.tet.2004.05.024

DO - 10.1016/j.tet.2004.05.024

M3 - Article

SN - 0040-4020

VL - 60

SP - 5953

EP - 5963

JO - Tetrahedron

JF - Tetrahedron

IS - 28

ER -

Synthesis of simple analogues of methyllycaconitine - An efficient method for the preparation of the N-substituted anthranilate pharmacophore

Abstract

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