326606-16-0Relevant articles and documents
Total synthesis of (+)-geldanamycin and (-)-o-quinogeldanamycin: Asymmetric glycolate aldol reactions and biological evaluation
Andrus, Merritt B.,Meredith, Erik L.,Hicken, Erik J.,Simmons, Bryon L.,Glancey, Russell R.,Ma, Wei
, p. 8162 - 8169 (2007/10/03)
The total synthesis of (+)-geldanamycin (GA), following a linear route, has been completed using a demethylative quinone-forming reaction as the last step. Key steps include the use of two new asymmetric boron glycolate aldol reactions. To set the anti-C11,12 hydroxymethoxy functionality, (S,S)-5,6-bis-4-methoxyphenyldioxanone 8 was used. Methylglycolate derived from norephedrine 5 set the C6,7 methoxyurethane stereochemistry. The quinone formation step using nitric acid gave the non-natural o-quino-GA product 55 10: 1 over geldanamycin. Other known oxidants gave an unusual azaquinone product 49. o-Quino-GA 55 binds Hsp90 with good affinity but is less cytotoxic compared to GA.
Synthesis of the left-hand portion of geldanamycin using an anti glycolate aldol reaction.
Andrus,Meredith,Sekhar
, p. 259 - 262 (2007/10/03)
[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.
