4375-07-9

Basic information

• Product Name: (5R)-5β-(3,4,5-Trimethoxyphenyl)-7α-(hydroxymethyl)-8α-hydroxy-5,6,7,8-tetrahydronaphtho[2,3-d]-1,3-dioxole-6β-carboxylic acid 6,7-lactone
• Synonyms: (-)-Epipodophyllotoxin;(5R)-5,5aα,8aβ,9-Tetrahydro-9α-hydroxy-5β-(3,4,5-trimethoxyphenyl)furo[3',4':6,7]naphtho[2,3-d]-1,3-dioxole-6(8H)-one;(5R)-5,8,8aβ,9-Tetrahydro-9α-hydroxy-5β-(3,4,5-trimethoxyphenyl)furo[3',4':6,7]naphtho[2,3-d]-1,3-dioxole-(5aαH)-one;(5R)-5β-(3,4,5-Trimethoxyphenyl)-7α-(hydroxymethyl)-8α-hydroxy-5,6,7,8-tetrahydronaphtho[2,3-d]-1,3-dioxole-6β-carboxylic acid 6,7-lactone;(5R,5aR,8aR,9S)-5,8,8a,9-Tetrahydro-5-(3,4,5-trimethoxyphenyl)-9-hydroxyfuro[3',4':6,7]naphtho[2,3-d]-1,3-dioxol-6(5aH)-one;Epipodophyllotoxin;(5S,5aR,8aR,9R)-5-hydroxy-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-8-one;(5S,5aR,8aR,9R)-5-hydroxy-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-isobenzofuro[5,6-f][1,3]benzodioxol-8-one
• CAS NO: 4375-07-9
• Molecular Formula: C₂₂H₂₂O₈
• Molecular Weight: 414.40528
• Product Categories: Aromatics, Heterocycles, Pharmaceuticals, Intermediates & Fine Chemicals
• Mol File: 4375-07-9.mol

Chemical Properties

• Melting Point: 160.3°C
• Boiling Point: 453.31°C (rough estimate)
• Appearance: /
• Density: 1.2649 (rough estimate)
• Refractive Index: 1.4480 (estimate)
• Storage Temp.: Hygroscopic, -20°C Freezer, Under inert atmosphere
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 13.26±0.40(Predicted)
• Stability: Hygroscopic
• CAS DataBase Reference: (5R)-5β-(3,4,5-Trimethoxyphenyl)-7α-(hydroxymethyl)-8α-hydroxy-5,6,7,8-tetrahydronaphtho[2,3-d]-1,3-dioxole-6β-carboxylic acid 6,7-lactone(CAS DataBase Reference)
• NIST Chemistry Reference: (5R)-5β-(3,4,5-Trimethoxyphenyl)-7α-(hydroxymethyl)-8α-hydroxy-5,6,7,8-tetrahydronaphtho[2,3-d]-1,3-dioxole-6β-carboxylic acid 6,7-lactone(4375-07-9)
• EPA Substance Registry System: (5R)-5β-(3,4,5-Trimethoxyphenyl)-7α-(hydroxymethyl)-8α-hydroxy-5,6,7,8-tetrahydronaphtho[2,3-d]-1,3-dioxole-6β-carboxylic acid 6,7-lactone(4375-07-9)

Safety Data

• Hazardous Substances Data: 4375-07-9(Hazardous Substances Data)

Usage

Uses

Epipodophyllotoxins is a naturally occuring antitumors agent extracted from Mayapple plant.

Anticancer Research

It is a lignan compound; podophyllotoxin is isolated from the roots of Podophyllumpeltatum and P. emodi. Teniposide and etoposide are the semisynthetic derivativesof epipodophyllotoxin, and they are used for lymphomas and bronchial and testicularcancers (Shoeb 2006). These compounds break DNA molecules during the G2/Mphase in cell cycle by binding to tubulin and irreversibly inhibiting DNAtopoisomerase II (Balunas and Kinghorn 2005). Podophyllotoxin prevents thebreast cancer cell growth by modifying checkpoint kinase 2 (Chk2) signalingpathway and also induces apoptosis in non-small cell lung cancer by cell cyclearrest, autophagy, and ER stress (Singh et al. 2016b).

Upstream product

• 1180-35-4 epipodophyllotoxin acetate 
• 136031-37-3 (4aR,5R,6R,11bS)-2,2-Di-tert-butyl-6-(3,4,5-trimethoxy-phenyl)-4a,5,6,11b-tetrahydro-4H-1,3,8,10-tetraoxa-2-sila-cyclopenta[b]phenanthrene-5-carboxylic acid methyl ester 
• 106636-74-2 4-bromo-4-deoxypodophyllotoxin 
• 106636-74-2 4β-bromo-4-desoxypodophyllotoxin 
• 173524-35-1 (-)-Methyl epipodophyllate 
• 477-51-0 deoxypodophyllotoxin 
• 477-48-5 podophyllotoxone 
• 64-19-7 acetic acid 
• 518-28-5 podofilox 
• 7401-22-1 9-Chloro-9-desoxypodophyllotoxin 
• 4375-06-8 epipicropodophyllotoxin 
• 581069-45-6 6.7-Methylendioxy-1-<3.4.5-trimethoxy-phenyl>-1.2-dihydro-naphthoesaeure-(2)-methylester 
• 2675-79-8 1-bromo-3,4,5-trimethoxybenzene 
• 116097-18-8 6,7-methylenedioxy-1-(3',4',5'-trimethoxyphenyl)-2-benzopyran-3-one 

Downstream Products

• 4375-06-8 epipicropodophyllotoxin 
• 78216-00-9 acetyl-epipicropodophyllotoxin 
• 1180-35-4 epipodophyllotoxin acetate 
• 1180-34-3 podophyllotoxinyl acetate 
• 136723-80-3 4-deoxy-4-allyl-(epi)-podophyllotoxin 
• 1174-96-5 6,7-O-Demethylen-epipodophyllotoxin 
• 138456-91-4 6,7-O,O-demethylene-4'-O-demethylepipodophyllotoxin 
• 477-48-5 podophyllotoxone 
• 78339-52-3 epipodophyllol 
• 518-28-5 podofilox 
• 78391-86-3 neoanhydropicropodophyllol 
• 62287-47-2 neoanhydropodophyllol 
• 154462-13-2 epipicropodophyllol 
• 38491-90-6 (5R,5aR,8aS,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl acetate 

Relevant articles and documents

Total synthesis of podophyllotoxin and select analog designs via C–H activation

An account of our previously disclosed total synthesis of the aryltetralin lignan natural product podophyllotoxin, a building block used in the synthesis of the FDA-approved anticancer drug etoposide, is disclosed. A C–H activation disconnection was viewed as being amenable to the preparation of E-ring modified analogs but proved challenging to execute. Various insights into palladium-catalyzed C–H arylation reactions on complex scaffolds are reported ultimately leading to the implementation of this strategy and the synthesis of compounds inaccessible by semisynthetic means.

Chemoenzymatic Total Synthesis of Deoxy-, epi-, and Podophyllotoxin and a Biocatalytic Kinetic Resolution of Dibenzylbutyrolactones

Podophyllotoxin is probably the most prominent representative of lignan natural products. Deoxy-, epi-, and podophyllotoxin, which are all precursors to frequently used chemotherapeutic agents, were prepared by a stereodivergent biotransformation and a biocatalytic kinetic resolution of the corresponding dibenzylbutyrolactones with the same 2-oxoglutarate-dependent dioxygenase. The reaction can be conducted on 2 g scale, and the enzyme allows tailoring of the initial, “natural” structure and thus transforms various non-natural derivatives. Depending on the substitution pattern, the enzyme performs an oxidative C?C bond formation by C?H activation or hydroxylation at the benzylic position prone to ring closure.

Stereoselective synthesis of 4β-acyloxypodophyllotoxin derivatives as insecticidal agents

As our ongoing work on research of natural-product-based insecticidal agents, some 4α/β-acyloxypodophyllotoxin derivatives were synthesized, and were evaluated against the pre-third-instar larvae of B. mori, A. dissimilis and M. separate in vivo at the co

Divergent Asymmetric Syntheses of Podophyllotoxin and Related Family Members via Stereoselective Reductive Ni-Catalysis

A nickel-catalyzed reductive cascade approach to the efficient construction of diastereodivergent cores embedded in podophyllum lignans is developed for the first time. Their gram-scale access paved the way for unified syntheses of naturally occurring podophyllotoxin and other members.

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.

Synthesis and Biological evaluation of novel 4β-[(5-substituted)-1,2,3,4-tetrazolyl] podophyllotoxins as anticancer compounds

A series of novel 4β-[(5-substituted)-1,2,3,4-tetrazolyl] podophyllotoxin derivatives were synthesized by employing azide-nitrile click chemistry approach. All the derivatives were evaluated for their cytotoxicity against a panel of four human cancer cell lines and their IC50 values were found to be in the range of 2.4-29.06 μM. The cytotoxicity exhibited by the majority of test compounds were found to comparable and often more effective than doxorubicin and all compounds exhibited higher cytotoxicity on A-549 cell lines. Cell cycle analysis showed that the novel 4β-[(5-substituted)-1,2,3,4-tetrazolyl] podophyllotoxins resulted in cell cycle arrest at G2/M phase and were also found to be the potent inhibitors of tubulin polymerization in vitro.

Differential Targeting of Human Topoisomerase II Isoforms with Small Molecules

(Chemical Equation Presented). The TOP2 poison etoposide has been implicated in the generation of secondary malignancies during cancer treatment. Structural similarities between TOP2 isoforms challenge the rational design of isoform-specific poisons to further delineate these processes. Herein, we describe the synthesis and biological evaluation of a focused library of etoposide analogues, with the identification of two novel small molecules exhibiting TOP2B-dependent toxicity. Our findings pave the way toward studying isoform-specific cellular processes by means of small molecule intervention.

One-pot synthesis of podophyllotoxin-thiourea congeners by employing NH2SO3H/NaI: Anticancer activity, DNA topoisomerase-II inhibition, and apoptosis inducing agents

A facile one-pot method for the synthesis of novel podophyllotoxin-thiourea congeners has been developed by using NH2SO3H/NaI system. Interestingly, 4β-azido podophyllotoxin reduction with concomitant aryl isothiocyanates coupling un

Synthesis and biological evaluation of 4β-benzoxazolepodophyllotoxin hybrids as DNA topoisomerase-II targeting anticancer agents

A series of new 4β-benzoxazolepodophyllotoxin compounds (9a-j) were prepared and screened for cytotoxicity against four human tumour cell lines (HeLa, DU-145, A-159 and MCF-7). Among these compounds, 9a, 9c, 9f and 9i have shown more potent anticancer activity than etoposide with considerable IC50 values. Apoptosis evaluation studies were performed using the Hoechst-33258 staining method and it was found specially that the best active compound 9i shows clear nuclear damage compared to etoposide. Molecular docking studies were also carried out to recognize the interactions against DNA topoisomerase-II and it was found that the energy calculations were in good agreement with the observed IC50 value.