474411-00-2Relevant academic research and scientific papers
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.
Total synthesis of (+)-geldanamycin and (-)-o-quinogeldanamycin with use of asymmetric anti- and syn-glycolate aldol reactions
Andrus, Merritt B.,Meredith, Erik L.,Simmons, Bryon L.,Sekhar, B. B. V. Soma,Hicken, Erik J.
, p. 3549 - 3552 (2007/10/03)
(matrix presented) Geldanamycin (GA), an antitumor Hsp90 inhibitor, was made for the first time by using an oxidative demethylation reaction as the final step. A biaryldioxanone auxiliary set the anti C11-12 hydroxy-methoxy functionality and a methylglycolate auxiliary based on norephedrine was used for the syn C6-7 methoxy-urethane. p-Quinone-forming oxidants, CAN and AgO, produced an unusual aza-quinone product. Nitric acid gave GA from a trimethoxy precursor in 55% yield as a 1:10 mixture with nonnatural o-quino-GA.
