Comprehensive synthetic route to eight diastereomeric Podophyllum lignans

Forsey, Steven P.; Rajapaksa, D.; Taylor, Nicholas J.; Rodrigo, R.

doi:10.1021/jo00279a011

Cited by 73 publications

(40 citation statements)

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“…It was concluded that product (3) was the lactone-opened derivate of podophyllotoxin. The 1 H and 13 C NMR data of product (3) was consistent with those of podophyllic acid, which is the lactone opening product of podophyllotoxin [29,30,32]. Therefore, biotransformation product (3) was identified as podophyllic acid, formed in the carbonyl group hydrolization of podophyllotoxin.…”

Section: Resultssupporting

confidence: 52%

Novel biotransformation process of podophyllotoxin to produce podophyllic acid and picropodophyllotoxin by Pseudomonas aeruginosa CCTCC AB93066. Part I: Process development

Tang

Zhong

2008

Bioprocess Biosyst Eng

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A novel biotransformation process of podophyllotoxin (1) to produce picropodophyllotoxin (2) and podophyllic acid (3) was developed in this work. Eight bacteria which could modify the structure of podophyllotoxin were screened out from the tested fourteen bacteria. The highest conversion of podophyllotoxin (i.e., 70.2 +/- 8.0%) was obtained when Pseudomonas aeruginosa CCTCC AB93066 was used as biocatalyst, so P. aeruginosa was selected as a typical biocatalyst in the following study. Product (2) and (3) were separated through D312 macroporous resin and sephadex LH-20 gel column chromatograph. On the basis of (1)H NMR, (13)C NMR, ESI-MS and Elemental Analysis, product (2) and (3) were identified as picropodophyllotoxin (2) and podophyllic acid (3), respectively. This suggested the site-specific isomerization and hydrolization of podophyllotoxin occurred during its biotransformation process by P. aeruginosa. For the first time, podophyllotoxin was biotransformed into its hydrolytic derivate (i.e., podophyllic acid).

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Section: Resultssupporting

confidence: 52%

Novel biotransformation process of podophyllotoxin to produce podophyllic acid and picropodophyllotoxin by Pseudomonas aeruginosa CCTCC AB93066. Part I: Process development

Tang

Zhong

2008

Bioprocess Biosyst Eng

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“…In 4-aryltetralin-type lignans having a fused 2,3-g-lactone moiety, the J 2,3 -values of the 2,3-cis-g-lactone derivatives were reported to be about 9.3-9.6 Hz and those of the 2,3-transg-lactone series about 14.8-15.5 Hz. [5][6][7][8][9] According to these reported data, the J 2,3 -value (9.5 Hz) of 1 suggested that 1 carries a 2,3-cis-g-lactone moiety in the molecule. Analogously, the J 3,4 -value (3.0 Hz) of 1 was consistent with the reported values for the 3,4-trans-configuration in 4-aryltetralin lignans with the 2,3-cis-g-lactone.…”

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confidence: 90%

A New and Known Cytotoxic Aryltetralin-Type Lignans from Stems of Bursera graveolens

Nakanishi

Inatomi

Murata

et al. 2005

CHEMICAL & PHARMACEUTICAL BULLETIN

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The genus Bursera (in Burseraceae) comprises about 40 species distributed in tropical zones of Latin and South America. Some species in this genus are used as perfumes and folk medicines.1) Bursera graveolens HBK is a wild tree native from Mexico and Yucatan to Peru and Venezuela and has been used as a remedy for stomach ache, sudorific, and a liniment for rheumatism.2) In the previous paper, 3) we reported the isolation of luteolin 3Ј-O-a-L-rhamnopyranoside and three of its new acylated derivatives along with four known flavonol glycosides from leaves of B. graveolens, and the inhibitory activity of the isolated compounds for the Maillard reaction.In our continuing study on B. graveolens, we found that the MeOH extract from the stems showed a potent cytotoxic activity in in vitro assay (vide post). This finding prompted us to investigate the chemical components in the MeOH extract of the stems and, as a result, a new podophyllotoxin-like 4a-aryltetralin-type lignan termed burseranin (1) and a known analogous lignan picropolygamain (2) were isolated together with two known triterpenes. In the present report, we describe the isolation, the structural determination, and biological activity of the isolated compounds in detail. The MeOH extract was partitioned with AcOEt and water. The AcOEt soluble part was subjected to repeated separation by silica gel columns, followed by a Sep-Pak octadecyl silica gel (ODS) column to afford 1 and 2 together with known triterpenes, lupeol and epi-lupeol.Burseranin 1, a colorless waxy solid, gave the molecular ion peak at m/z 382 (M (Table 1). A carbon signal at d C 178.3, reasonably assigned to a g-lactone carbonyl carbon in the 13 C-NMR spectrum (Table 1), 4) in conjunction with detailed two dimensional (2D) analysis by the 1 H-1 H correlation spectroscopy (COSY), heteronuclear multiquantum coherence (HMQC), and heteronuclear multiple bond connectivity (HMBC) (Fig. 1), gave the podophillotoxin-like planar structure for 1 shown in Fig. 1. Furthermore, nuclear Overhauser enhancement spectroscopy (NOESY) correlations observed between H-4 and H-5 and between H-4 and H-2Ј also supported the validity of this established plane structure. The relative structure of 1 was determined based on the 1 H coupling constants (J values) and the NOESY data as follows. In 4-aryltetralin-type lignans having a fused 2,3-g-lactone moiety, the J 2,3 -values of the 2,3-cis-g-lactone derivatives were reported to be about 9.3-9.6 Hz and those of the 2,3-transg-lactone series about 14.8-15.5 Hz. [5][6][7][8][9] According to these reported data, the J 2,3 -value (9.5 Hz) of 1 suggested that 1 carries a 2,3-cis-g-lactone moiety in the molecule. Analogously, the J 3,4 -value (3.0 Hz) of 1 was consistent with the reported values for the 3,4-trans-configuration in 4-aryltetralin lignans with the 2,3-cis-g-lactone.6-9) Furthermore, the va- A new 4a a-aryltetralin-type lignan called burseranin (1) and a known analogous lignan picropolygamain (2) were isolated along with known triterpenes, lupeol and epi-lupeol f...

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“…The main decomposition product most probably was picropodophyllin, based on the comparison of its HPLC-retention time behaviour with that of a sample of authentic picropodophyllin. It is known that podophyllotoxin is rapidly converted into picropodophyllin, its more stable cis-form by epimerization of the trans-lactone ring (Buchardt et al 1986;Forsey et al 1989). Therefore, it was concluded that the most convenient method to prepare cyclodextrin-complexed podophyllotoxin is by shaking, where no decomposition was found.…”

Section: Resultsmentioning

confidence: 99%

Glucosylation of cyclodextrin-complexed podophyllotoxin by cell cultures of Linum flavum L.

Uden

Oeij

Woerdenbag

et al. 1993

Plant Cell Tiss Organ Cult

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The glucosylation of the cytotoxic lignan podophyllotoxin by cell cultures derived from Linum flavum was investigated. Four cyclodextrins: /3-cyclodextrin, y-cyclodextrin, dimethyl-/3-cyclodextrin and hydroxypropyl-/3-cyclodextrin were used to improve the solubility of podophyllotoxin by complexation. Dimethyl-/3-cyclodextrin met our needs the best and the solubility of podophyllotoxin could be enhanced from 0.15 to 1.92 mM, using a podophyllotoxin/cyclodextrin ratio of 1 : 1. Growth parameters of the cell suspensions were not affected neither by the addition of cyclodextrins alone, nor when complexed podophyllotoxin was dissolved in the medium.The complexed lignan disappeared rapidly from the culture medium, within 24h, under all experimental conditions. Almost simultaneously, between 73 and 100% of detectable podophyllotoxin was bioconverted into podophyllotoxin-/3-D-glucoside. A maximal bioconversion rate of 0.51 mmol 1-1 suspension day -1 was calculated for the L. flavum cells growing in a medium which included the podophyllotoxin/dimethyl-/3-cyclodextrin complex at a final concentration of 1.35 mM.

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Comprehensive synthetic route to eight diastereomeric Podophyllum lignans

Cited by 73 publications

References 0 publications

Novel biotransformation process of podophyllotoxin to produce podophyllic acid and picropodophyllotoxin by Pseudomonas aeruginosa CCTCC AB93066. Part I: Process development

Novel biotransformation process of podophyllotoxin to produce podophyllic acid and picropodophyllotoxin by Pseudomonas aeruginosa CCTCC AB93066. Part I: Process development

A New and Known Cytotoxic Aryltetralin-Type Lignans from Stems of Bursera graveolens

Glucosylation of cyclodextrin-complexed podophyllotoxin by cell cultures of Linum flavum L.

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