Synthesis of the left-hand portion of geldanamycin using an anti glycolate aldol reaction.
[figure: see text] A synthesis of the left-hand portion of the ansamycin antitumor natural product geldanamycin is reported. An advanced intermediate incorporates the methoxyquinone precursor as a pentasubstituted benzene with a 10-carbon chain that contains 4 of the 6 stereocenters. The key reaction is a novel anti glycolate aldol reaction with a new diaryl-4-oxapyrone used to generate the C-11, C-12 hydroxy, methoxy functionality.
Andrus
M B
MB
Department of Chemistry and Biochemistry, C100 BNSN, Brigham Young University, Provo, Utah 84602, USA. mbandrus@chemdept.byu.edu
Meredith
E L
EL
Sekhar
B B
BB
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry; D016227:Benzoquinones; D002625:Chemistry, Organic / Q000379:methods; D007202:Indicators and Reagents; D047029:Lactams, Macrocyclic; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011809:Quinones / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000970:Antineoplastic Agents; D016227:Benzoquinones; D007202:Indicators and Reagents; D047029:Lactams, Macrocyclic; D011809:Quinones; C001277:geldanamycin