Total synthesis of (−)-salicylihalamide A and related congeners

• Published in: Tetrahedron Vol. 58; no. 32; pp. 6455 - 6471
• Main Authors: Smith, Amos B, Zheng, Junying
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 05-08-2002
• Subjects: Curtius rearrangement; macrocycles; metathesis; salicylihalamide; total synthesis; Curtius rearrangement; total synthesis; salicylihalamide; metathesis; macrocycles
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/S0040-4020(02)00657-9

A concise, highly efficient total synthesis of (−)-salicylihalamide A (
1
), a novel marine sponge metabolite, has been achieved. Key features of the synthetic strategy include a highly
E-selective ring-closing metathesis to construct the 12-membered salicylihalamide A macrocycle and a practical method for installation of the labile ene-hepta-(
Z,
Z)-dienamide side chain involving
N-acylation of enecabarmate
5
, the latter derived from the corresponding α,β-unsaturated carboxylic acid
28
via acyl azide formation and thermal Curtius rearrangement. Two structurally simplified analogs (
3
and
4
) were also prepared which displayed significant, but attenuated cell growth inhibitory activity against several human tumor cell lines.
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