112246-49-8

Upstream product

• 163959-36-2 etoposide 
• 112146-43-7 Chloro-acetic acid (2S,4aS,6S,7S,8R,8aS)-7-(2-chloro-acetoxy)-6-hydroxy-2-methyl-hexahydro-pyrano[3,2-d][1,3]dioxin-8-yl ester 
• 92206-82-1 Chloro-acetic acid 4-((5S,5aS,9R)-9-hydroxy-6-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 
• 477-47-4 (+/-)-podophyllotoxin 
• 6559-91-7 (+/-)-4'-O-demethyl-1-epipodophyllotoxin 
• 149312-27-6 4,6-O-ethylidene-1,2,3-tri-O-(dichloroacetyl)-α-D-glucopyranose 
• 149312-24-3 1-O-(trimethylsilyl)-4,6-O-ethylidene-2,3-di-O-(dichloroacetyl)-β-D-glucopyranose 
• 18465-50-4 4,6-O-ethylidene-D-glucopyranose 

Relevant academic research and scientific papers

Preparation method of etoposide, teniposide and analogs of etoposide and teniposide

The invention discloses a preparation method of etoposide, teniposide and analogs of etoposide and teniposide. The preparation method includes the following steps of 1, selective protection of 4'domethylpodophyllotoxin4'hydroxy; 2, introduction of 4 hydroxy hydroxyl; 3, removal of a protecting group. The method is mild in reaction condition and environmentally friendly, and the yield and purity of the products are high.

Protease-mediated fragmentation of p-amidobenzyl ethers: A new strategy for the activation of anticancer prodrugs

A new anticancer prodrug activation strategy based on the 1,6-elimination reaction of p-aminobenzyl ethers is described. Model studies were undertaken with the N-protected peptide benzyloxycarbonylvaline-citrulline (Z-val-cit), which was attached to the amino groups of p-aminobenzyl ether derivatives of 1-naphthol and N-acetylnorephedrine. The amide bond that formed was designed for hydrolysis by cathepsin B, a protease associated with rapidly growing and metastatic carcinomas. Upon treatment with the enzyme, the Z-val-cit-p-amidobenzyl ether of 1-naphthol (2) underwent peptide bond hydrolysis with the rapid release of 1-naphthol. The aliphatic Z-val-cit-p-amidobenzyl ether of N-acetylnorephedrine (5) also underwent amide bond hydrolysis, but without the ensuing elimination of N-acetylnorephedrine. On the basis of these results, the phenolic anticancer drugs etoposide (6) and combretastatin A-4 (7) were attached to the Z-val-cit-p-amidobenzyl alcohol through ether linkages, forming the peptide-drug derivatives 8 and 9, respectively. Both compounds were stable in aqueous buffers and serum and underwent ether fragmentation upon treatment with cathepsin B, resulting in the release of the parent drugs in chemically unmodified forms. The released drugs were 13-50 times more potent than were the prodrug precursors on a panel of cancer cell lines. In contrast, the corresponding carbonate derivative of combretastatin A-4 (13) was unstable in aqueous environments and was as cytotoxic as combretastatin A-4. This result extends the use of the self-immolative p-aminobenzyl group for the fragmentation of aromatic ethers and provides a new strategy for anticancer prodrug development.

Syntheses of All Four Possible Diastereomers of Etoposide and Its Aminoglycosidic Analogues via Optical Resolution of (+/-)-Podophyllotoxin by Glycosidation with D- and L-Sugars

Syntheses of all four possible diastereomers of etoposide and its aminoglycosidic analogues have been achieved via optical resolution of (+/-)-podophyllotoxin by glycosidation with D- and L-sugars.