Total synthesis of herbimycin A.
[structure: see text] Hsp90 has recently emerged as a promising biological target for treatment of cancer. Herbimycin A and other members of the benzoquinoid ansamycin class of natural products are known to inhibit Hsp90 activity. The total synthesis of herbimycin A was achieved from the commercially available Roche ester 1 by using allylmetals to control the stereogenic centers at C6, C7, C10, C11, and C12 and a ring-closing metathesis to control the (Z)-double bond of the (E,Z)-dienic moiety.
Canova
Sophie
S
Laboratoire de Chimie Organique, associé au CNRS, ESPI, 10 rue Vauquelin, 75231 Paris Cedex 05, France.
Bellosta
Véronique
V
Bigot
Antony
A
Mailliet
Patrick
P
Mignani
Serge
S
Cossy
Janine
J
D016227:Benzoquinones / Q000138:chemical synthesis* / Q000737:chemistry; D002244:Carbon / Q000737:chemistry; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D047029:Lactams, Macrocyclic / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D017828:Rifabutin / Q000031:analogs & derivatives
D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D017828:Rifabutin; C020754:herbimycin; D002244:Carbon; C001277:geldanamycin