Total synthesis of myxothiazols, novel bis-thiazole beta-methoxyacrylate-based anti-fungal compounds from myxobacteria

Convergent total syntheses of myxothiazols A and Z are described. The syntheses are based on elaboration of the (S)-E,E-diene thioamide 22, conversion of 22 into the bis-thiazole 27 and Wittig reactions between 27c and the aldehyde 30. The substituted beta-methoxyacrylate aldehyde 30 was produced vi...

Full description

Saved in:
Bibliographic Details
Published in:Organic & biomolecular chemistry 2006-08, Vol.4 (15), p.2906-2911
Main Authors: Clough, John M, Dube, Henry, Martin, Bruce J, Pattenden, Gerald, Reddy, K Srinivasa, Waldron, Ian R
Format: Article
Language:English
Subjects:
Antifungal Agents - chemical synthesis
Antifungal Agents - pharmacology
Methacrylates - chemical synthesis
Methacrylates - pharmacology
Myxococcales - chemistry
Thiazoles - chemical synthesis
Thiazoles - pharmacology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Convergent total syntheses of myxothiazols A and Z are described. The syntheses are based on elaboration of the (S)-E,E-diene thioamide 22, conversion of 22 into the bis-thiazole 27 and Wittig reactions between 27c and the aldehyde 30. The substituted beta-methoxyacrylate aldehyde 30 was produced via an Evans asymmetric aldol protocol or via the 2H-pyran-2-one 31. An E-selective Wittig reaction between the ylide derived from the phosphonium salt 27c and the (+)-aldehyde 30 led to (+)-myxothiazol Z (1b), and a corresponding reaction with the (+/-)-acrylamide aldehyde 44 gave (+/-)-myxothiazol A (1a). Complementary studies led to synthesis of the ester 47b, corresponding to myxothiazol R and myxothiazol S.
ISSN:1477-0520
1477-0539
DOI:10.1039/b603433k