Aryltetralin Lignans: Chemistry, Pharmacology and Biotransformations

Abstract

Podophyllotoxin derivatives like etoposide 7a, etophos 7b, and teniposide 7c are used clinically as potent chemotherapeutic agents for a variety of tumors including small cell lung carcinoma, testicular cancer, and malignant lymphoma. These compounds derived from a series of modifications which converted podophyllotoxin 1a from an entity that interacted with tubulin and blocks mitosis to one that induced a block in late S or early G2 by interacting with topoisomerase II. Synthetic studies on podophyllotoxin derivatives can be divided in four general approaches (the oxo-ester route, the digydroxy acid route, the tandem conjugate addition route and the Diels-Alder route). Albeit a number of synthetic sequences afforded products with excellent enantiopurities, the low overall yields still disqualify synthesis as an alternative for naturally produced materials. An alternative route based on the enzyme-catalyzed cyclization of synthetic intermediates to analogues of the podophyllotoxin family is being explored. Synthetic dibenzylbutanolides, which were revealed by biosynthetic studies to be the precursors of aryltetralin lignans, have been treated with enzymes derived from cell cultures of Podophyllum peltatum, Catharanthus roseus, Nicotiana sylvestris and Cassia didymobotrya. The ciclyzation process afforded however compounds with a different stereochemistry in the C ring. The obtainment of a novel compound with a bynzylidenebenzylbutirolactone structure still leaves considerable scope for exploring biotransformations in order to obtain podophyllotoxin analogues via a combination of synthetic chemistry and biotechnological methods.

Electrospray Ionization Tandem Mass Spectrometry as a Tool for the Structural Elucidation and Dereplication of Natural Products: An Overview

“…Several biological activities, such as anti-tumoral, fungicide, and anti-viral actions, have been attributed to the presence of these compounds, (Ayres & Loike, 1990;Botta et al, 2001;Pan et al, 2009). Shengmai San (SMS), a prescription comprised of Panax ginseng, Schisandra chinensis, and Ophiopogon japonicus, has long been used in traditional Chinese medicine.…”

Diastereoselective synthesis of β-piperonyl-γ-butyrolactones from morita-baylis-hillman adducts. highly efficient synthesis of (±)-yatein, (±)-podorhizol and (±)-epi-podorhizol

“…The combined organic phases were removed and the crude was redissolved in ethyl acetate (50 mL). The organic phase was washed with distilled water (25 mL), brine (25 mL) and finally dried over anhydrous Na 2 …”

“…These secondary metabolites are widely encountered in plant kingdom and present a huge structural diversity normally associated with interesting biological effects, such as antitumoral, fungicide and anti-viral. 1,2 Furthermore, they also show other biological activities against insects and some vertebrates ( Figure 1). 3 Trachelogenin amide A (1, Figure 1) is a dibenzylbutane lignan, isolated from the leaves and stems of Trachelospermum jasminoides.…”

Podophyllotoxin and Antitumor Synthetic Aryltetralines. Toward a Biomimetic Preparation

“…This suggested that their antitumor properties were due to another mechanism of action: their interaction with DNA. In fact, they induce a block in late phase S or early G2 by interacting with the enzyme topoisomerase II (Botta et al, 2001). DNA topoisomerases are nuclear enzymes which make transient DNA strand breaks, allowing the cell to manipulate the topology of its DNA.…”