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Protecting-group strategies for the synthesis of N4-substituted, and N1,N8-disubstituted spermidines, exemplified by hirudonine

Lookup NU author(s): Professor Bernard Golding, Emeritus Professor Bill Clegg, Dr Mark Elsegood, Professor Roger Griffin

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Abstract

Methods are described for the preparation of derivatives of the polyamines 1,4-diaminobutane (putrescine), and N′-(3-amihopropyl)-l,4-diaminobutane (spermidine) in which a particular amino group is modified with, e.g., a guanidino function. Specific amino groups in these polyamines were protected as ;V-trifluoroacetyl, and yV-4-azidobenzyloxycarbonyl derivatives, which were unmasked chemoselectively using methanolic ammonia, and dithiothreitol-triethylamine, respectively. Guanidino functions were introduced by an improved procedure in which an amino group was treated with 3,5-dimethyl-Ar-nitro-!//-pyrazole-l-carboximidamide in methanol to give a nitroguanidine derivative, from which the nitro group was removed by catalytic transfer hydrogénation. The methodology is exemplified by the development of efficient preparative routes to agmatine, and hirudonine. The integrity of the sequence of protection/deprotection leading to hirudonine was confirmed by a crystal-structure analysis of its sulfate. The effect of selected compounds on the uptake of putrescine into rat lung cells was determined, and showed that N4-(4-azidobenzyloxycarbonyl)spermidine was the best inhibitor (Ki = 3.4 μM).


Publication metadata

Author(s): Golding BT, Mitchinson A, Clegg W, Elsegood MRJ, Griffin RJ

Publication type: Article

Publication status: Published

Journal: Journal of the Chemical Society - Perkin Transactions 1

Year: 1999

Issue: 3

Pages: 349-356

Print publication date: 01/01/1999

ISSN (print): 0300-922X

ISSN (electronic): 1364-5463

Publisher: Royal Society of Chemistry

URL: http://dx.doi.org/10.1039/a806355i

DOI: 10.1039/a806355i


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