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 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.
Clough
John M
JM
School of Chemistry, University of Nottingham, University Park, UK.
Dube
Henry
H
Martin
Bruce J
BJ
Pattenden
Gerald
G
Reddy
K Srinivasa
KS
Waldron
Ian R
IR
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D008689:Methacrylates / Q000138:chemical synthesis / Q000494:pharmacology; D009231:Myxococcales / Q000737:chemistry*; D013844:Thiazoles / Q000138:chemical synthesis / Q000494:pharmacology
D000935:Antifungal Agents; D008689:Methacrylates; D013844:Thiazoles; C030517:myxothiazol