642409-76-5

Upstream product

• 153230-70-7 4,4'-bis-O-(dimethyl-tert-butylsilyl)-4'-O-demethylepipodophyllotoxin 
• 642409-81-2 2,2-dimethyl-propionic acid 8-(tert-butyl-dimethyl-silanyloxy)-5-[4-(tert-butyl-dimethyl-silanyloxy)-3,5-dimethoxy-phenyl]-7-formyl-5,6,7,8-tetrahydro-naphtho[2,3-d][1,3]dioxol-6-ylmethyl ester 
• 642409-78-7 2,2-dimethyl-propionic acid 8-(tert-butyl-dimethyl-silanyloxy)-5-[4-(tert-butyl-dimethyl-silanyloxy)-3,5-dimethoxy-phenyl]-7-hydroxymethyl-5,6,7,8-tetrahydro-naphtho[2,3-d][1,3]dioxol-6-ylmethyl ester 
• 642409-82-3 5-(tert-butyl-dimethyl-silanyloxy)-8-[4-(tert-butyl-dimethyl-silanyloxy)-3,5-dimethoxy-phenyl]-7-(2,2-dimethyl-propionyloxymethyl)-5,6,7,8-tetrahydro-naphtho[2,3-d][1,3]dioxole-6-carboxylic acid 
• 642409-83-4 5-(tert-butyl-dimethyl-silanyloxy)-8-[4-(tert-butyl-dimethyl-silanyloxy)-3,5-dimethoxy-phenyl]-7-hydroxymethyl-5,6,7,8-tetrahydro-naphtho[2,3-d][1,3]dioxole-6-carboxylic acid 
• 153230-77-4 4,4'-bis(tert-butyldimethylsilyl)-4'-O-demethylepipodophyllol 
• 845863-32-3 4-O-(tert-butyldimethylsilyl)-11-oxo-13-deoxo-4'-demethylepipodophyllotoxin 
• 642409-84-5 5-(tert-butyl-dimethyl-silanyloxy)-9-[4-(tert-butyl-dimethyl-silanyloxy)-3,5-dimethoxy-phenyl]-5,8,8a,9-tetrahydro-5aH-furo[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6-one 

Downstream Products

• 642409-85-6 11-oxo-13-deoxo-4'-benzyloxycarbonyl-4'-demethylepipodophyllotoxin 
• 845863-43-6 11-oxo-13-deoxo-4'-demethyl-4'-benzyloxycarbonyl-4β-(formylmethyl)-4-desoxypodophyllotoxin 
• 845863-41-4 11-oxo-13-deoxo-4'-demethyl-4'-benzyloxycarbonyl-4β-allyl-4-desoxypodophyllotoxin 
• 845863-42-5 Carbonic acid benzyl ester 4-[(5R,5aR,8aR,9S)-9-(2,3-dihydroxy-propyl)-8-oxo-5,5a,6,8,8a,9-hexahydro-furo[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl]-2,6-dimethoxy-phenyl ester 
• 845863-35-6 11-oxo-13-deoxo-4'-benzyloxycarbonyl-4'-demethylepipodophyllotoxin 4-[N-[2-(N',N'-dimethylaminoethyl)]-N-methyl]carbamate 
• 845863-36-7 11-oxo-13-deoxo-4'-benzyloxycarbonyl-4'-demethylepipodophyllotoxin 4-[N-(2-aminoethyl)]carbamate 
• 845863-44-7 11-oxo-13-deoxo-4'-demethyl-4'-benzyloxycarbonyl-4β-[2-[[2-(N',N'-dimethylamino)ethyl]amino]ethyl]-4-desoxypodophyllotoxin 
• 845863-34-5 11-oxo-13-deoxo-4'-benzyloxycarbonyl-4'-demethylepipodophyllotoxin 4-[N-[2-(N',N'-dimethylaminoethyl)]]carbamate 
• 845863-39-0 11-oxo-13-deoxo-4'-benzyloxycarbonyl-4'-demethylepipodophyllotoxin 4-[N-(3-aminopropyl)]carbamate 
• 845863-38-9 11-oxo-13-deoxo-4'-benzyloxycarbonyl-4'-demethylepipodophyllotoxin 4-[N-[3-(N',N'-dimethylaminopropyl)]-N-methyl]carbamate 
• 845863-37-8 11-oxo-13-deoxo-4'-benzyloxycarbonyl-4'-demethylepipodophyllotoxin 4-[N-[3-(N',N'-dimethylaminopropyl)]]carbamate 
• 845863-33-4 11-oxo-13-deoxo-4'-benzyloxycarbonyl-4'-demethylepipodophyllotoxin 4-(p-nitrophenyl)carbonate 

Relevant academic research and scientific papers

Synthesis and biological study of a new series of 4′- demethylepipodophyllotoxin derivatives

Etoposide (VP-16) is a potent human DNA topoisomerase II poison, derived from 4′-demethylepipodophyllotoxin, widely used in cancer chemotherapy. Continuous efforts have driven to synthesize new related compounds, presenting decreased toxic side effects, metabolic inactivation, drug resistance, and increased water solubility. Identified structure-activity relationships have pointed out the importance of the 4β-substitution and of the configuration of the D ring. Here we report the synthesis of two novel series of derivatives of 4′-demethylepipodophyllotoxin. The first bears a carbamate chain in the 4 position (13a-f), whereas, in the second series, in addition to this chain, the lactone ring has been modified by shifting the carbonyl from position 13 to position 11 (27a-f). Moreover, an analogue of TOP-53 having this lactone modification has also been prepared (32). From this study, structure-activity relationships were established. Compounds 13a and 27a displayed potent cytotoxic activity against the L1210 cell line (10 to 20-fold higher than VP-16) and proved to be strong topoisomerase II poisons more potent than VP-16. From preliminary in vivo investigation of both compounds against P388 leukemia and orthotopically grafted human A549 lung carcinoma, it appeared that 13a and 27a constitute promising leads for a new class of antitumor agents.

Synthesis and antiproliferative activity of retroetoposide

Retro-4′-demethyl-4-epipodophyllotoxin 6 was synthesized in eight steps and 10% overall yield from 4′-demethyl-4-epipodophyllotoxin 12. Subsequent coupling of 22 with 1-O-trimethylsilyl-4,6-O-ethylidene-β-D- glucoside 26 afforded retroetoposide 5 which is