326606-15-9

Upstream product

• 326606-14-8 (4S)-4-benzyl-3-[(2R)-2-methyl-3-(5-nitro-2,3,6-trimethoxyphenyl)-propionyl]-oxazolidin-2-one 
• 326606-24-0 (2,3,6-trimethoxy-5-nitrophenyl)methanol 
• 326606-13-7 5-nitro-2,3,6-trimethoxybenzyl bromide 
• 326606-12-6 2,3,6-trimethoxy-5-nitrobenzaldehyde 
• 5556-86-5 2,3,6-trimethoxybenzaldehyde 
• 135-77-3 1,2,4-trimethoxy-benzene 
• 75-86-5 2-hydroxy-2-methylpropanenitrile 
• 326606-25-1 (2R)-2-methyl-3-(5-nitro-2,3,6-trimethoxy-phenyl)-propan-1-ol 

Downstream Products

• 326606-26-2 (3S,5S,6S)-3-[(1S,3R)-1-methoxy-3-methyl-4-(5-nitro-2,3,6-trimethoxy-phenyl)-butyl]-5,6-bis-(4-methoxy-phenyl)-[1,4]dioxan-2-one 
• 326606-17-1 (3S,5S,6S)-3-[(1S,3R)-1-methoxy-3-methyl-4-(5-nitro-2,3,6-trimethoxy-phenyl)-butyl]-5,6-bis-(4-methoxy-phenyl)-[1,4]dioxan-2-ol 
• 326606-16-0 (3S,5S,6S)-3-[(1S,3R)-1-hydroxy-3-methyl-4-(5-nitro-2,3,6-trimethoxy-phenyl)-butyl]-5,6-bis-(4-methoxy-phenyl)-[1,4]dioxan-2-one 
• 326606-09-1 (4R,5S,7R)-4-(tert-butyl-dimethyl-silanyloxy)-5-methoxy-7-methyl-8-(5-nitro-2,3,6-trimethoxy-phenyl)-oct-2-enoic acid methyl ester 
• 326606-21-7 (2R,3S,5R)-3-methoxy-2-(2-methoxy-ethoxymethoxy)-5-methyl-6-(5-nitro-2,3,6-trimethoxy-phenyl)-hexan-1-ol 
• 326606-22-8 (2S,3S,5R)-3-Methoxy-2-(2-methoxy-ethoxymethoxy)-5-methyl-6-(2,3,6-trimethoxy-5-nitro-phenyl)-hexanal 
• 326606-27-3 (4R,5S,7R)-4-hydroxy-5-methoxy-7-methyl-8-(5-nitro-2,3,6-trimethoxy-phenyl)-oct-2-enoic acid methyl ester 
• 326606-20-6 (2R,3S,5R)-3-methoxy-5-methyl-6-(5-nitro-2,3,6-trimethoxy-phenyl)-hexan-1,2-diol 
• 326606-10-4 (3R)-3-methyl-4-(5-nitro-2,3,6-trimethoxyphenyl)-butyraldehyde 

Relevant academic research and scientific papers

Total synthesis of (+)-geldanamycin and (-)-o-quinogeldanamycin: Asymmetric glycolate aldol reactions and biological evaluation

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

(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.

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.