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Issue 20, 2005
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The diazo route to diazonamide A: studies on the tyrosine-derived fragment

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Various approaches to the tyrosine-derived fragment of the marine secondary metabolite diazonamide A are described. Initial efforts were focused on the originally proposed structure of the natural product, and a feasibility study established that a model 4-aryltryptamine could be readily prepared. Protected 4-bromotryptamine underwent Pd(0)-catalyzed coupling with the boronic acid derived from 2-bromophenyl allyl ether by Claisen rearrangement, O-methylation and lithiation–boration. The resulting biaryl was elaborated into an α-diazo-β-ketoester, dirhodium(II)-catalyzed reaction of which with N-Z-valinamide gave the desired tryptamine-oxazole following cyclodehydration of the intermediate ketoamide. A potential precursor to the benzofuran ring of the original structure of diazonamide A was prepared in eight steps from N-Z-tyrosine tert-butyl ester. Iodination, O-protection and Stille coupling gave the cinnamyl alcohol 25, converted via the bromide into the allyl aryl ether 27. Subsequent Claisen rearrangement and oxidative cleavage of the alkene gave the lactol 29, converted into the desired benzofuranone 31. The revision in the structure of diazonamide A to 2 resulted in the targeting of an alternative tyrosine-derived model benzofuranone 41 synthesized in four steps from N-Z-tyrosine methyl ester 36 by a route involving Claisen rearrangement of cinnamyl ether 37. Poor yields in this sequence prompted an investigation into the intramolecular Heck reaction as a route to benzofuranone 50. Coupling of 3-iodotyrosine 44 with 2-phenylbutenoic acid 48 gave ester 49 that readily underwent intramolecular Heck reaction to give benzofuranone 50, albeit with poor stereocontrol.

Graphical abstract: The diazo route to diazonamide A: studies on the tyrosine-derived fragment

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Article information

27 Jul 2005
22 Aug 2005
First published
14 Sep 2005

Org. Biomol. Chem., 2005,3, 3805-3811
Article type

The diazo route to diazonamide A: studies on the tyrosine-derived fragment

F. N. Palmer, F. Lach, C. Poriel, A. G. Pepper, M. C. Bagley, A. M. Z. Slawin and C. J. Moody, Org. Biomol. Chem., 2005, 3, 3805
DOI: 10.1039/B510653B

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