869732-34-3

Upstream product

• 869732-19-4 (4E,8S,9S,10E,12S,13R,14S,16R)-20-(benzyloxy)-9-(tert-butyldimethylsilyloxy)-13-(methoxymethoxy)-4,10,12,16-tetramethyl-8,14,19-trimethoxy-2-aza-bicyclo[16.3.1]docosa-1⁽²¹⁾,4,10,18⁽²²⁾,19-pentaen-3-one 
• 869732-11-6 (6S,2E)-ethyl 6-methoxy-2-methyl-7-oxohept-2-enoate 
• 869732-22-9 (6S,2E)-ethyl 6-methoxy-2-methyl-7-hydroxyhept-2-enoate 
• 869732-13-8 3-(benzyloxy)-5-bromo-2-methoxybenzaldehyde 
• 869732-12-7 (S,E)-ethyl 7-(tert-butyldimethylsilyloxy)-6-hydroxy-2-methylhept-2-enoate 
• 869732-21-8 (S,E)-ethyl 7-(tert-butyldimethylsilyloxy)-6-methoxy-2-methylhept-2-enoate 
• 869732-16-1 (2S,4R)-5-(3-(benzyloxy)-5-bromo-2-methoxyphenyl)-2-methoxy-4-methylpentanal 
• 869732-27-4 (2R,3S,5R)-6-(3-benzyloxy-5-bromo-2-methoxyphenyl)-3-methoxy-5-methylhexane-1,2-diol 
• 869732-17-2 (3S,4R,5S,7R)-8-(3-(benzyloxy)-5-bromo-2-methoxyphenyl)-5-methoxy-3,7-dimethyloct-1-en-4-ol 
• 869732-30-9 (2R,3R,4S,6R)-7-(3-Benzyloxy-5-bromo-2-methoxy-phenyl)-4-methoxy-3-methoxymethoxy-2,6-dimethyl-heptanal 
• 869732-28-5 1-Benzyloxy-5-bromo-2-methoxy-3-((2R,4S,5R,6S)-4-methoxy-5-methoxymethoxy-2,6-dimethyl-oct-7-enyl)-benzene 
• 56-86-0 L-glutamic acid 
• 24677-78-9 2,3-dihydroxybenzaldehyde 
• 1601460-55-2 (3R,5S)-3-(3-(benzyloxy)-5-bromo-2-methoxybenzyl)-5-(((tert-butyldimethylsilyl)oxy)methyl)tetrahydro-furan-2-ol 

Downstream Products

• 869732-20-7 (4E,8S,9S,10E,12S,13R,14S,16R)-carbamic acid 20-(benzyloxy)-13-(methoxymethoxy)-4,10,12,16-tetramethyl-8,14,19-trimethoxy-3-oxo-2-azabicyclo[16.3.1]docosa-1⁽²¹⁾,4,10,18⁽²²⁾,19-pentaen-9-yl ester 
• 869732-20-7 (4E,8S,9S,10E,12S,13R,14S,16R)-carbamic acid-20-(benzyloxy)-13-(methoxymethoxy)-4,10,12,16-tetramethyl-8,14,19-trimethoxy-3-oxo-2-azabicyclo[16.3.1]docosa-1⁽²¹⁾,4,10,18⁽²²⁾,19-pentaen-9-yl ester 

Relevant academic research and scientific papers

Total synthesis of reblastatin: Convenient preparation of coupling partners and scaled assembly

Potentially scalable total synthesis of reblastatin was achieved based on Panek's previous study. Novel and convenient synthetic routes were developed for the known C8-C20 and C1-C7 coupling partners. The challenging C8-C20 fragment was prepared from TBS

Synthesis of reblastatin, autolytimycin, and non-benzoquinone analogues: Potent inhibitors of heat shock protein 90

A full account of an asymmetric synthesis of reblastatin (1) and the first total synthesis of autolytimycin (2) and related structural compounds is described. The syntheses expand the utility of a highly regio- and diastereoselective hydrometalation aldehyde addition sequence to assemble the fully functionalized ansa chain of the natural products. Also documented is an intramolecular copper-mediated amidation reaction to close the 19-membered macrolactams. The amidation reaction was also employed for the generation of structural derivatives (6-9) of phenolic ansamycins. Ansamycin natural products and selected structural analogues were evaluated in a competitive binding assay to breast cancer cell lysate and a cytotoxicity assay. Both reblastatin (1) and autolytimycin (2) were shown to bind the heat shock protein 90 with enhanced binding activity (～25 nM) than 17-allylamino-17-demethoxygeldanamycin (17-AAG, 4), a geldanamycin (3) derivative currently under evaluation for treatment of cancer (～100 nM).

Total synthesis of reblastatin

Enantioselective total synthesis of reblastatin is described. The synthesis highlights hydrozirconation, transmetalation, aldehyde addition sequence to install E-trisubstituted olefin and C7 stereocenter, and the first use of an intramolecular Buchwald-like amidation reaction to close the 19-membered macrolactam. Copyright