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Treatment of calix[4]arene bis-O-carbamates 4a,b-6a,b with LDA in THF results in the regio- and stereoselective introduction of both axial and equatorial carboxamide groups at the methylene bridges via a homologous anionic ortho-Fries rearrangement to give 7-16. The stereochemical outcome of the rearrangement is dependent on the reaction conditions and the conformation of the starting material. Stereochemical and structural proof has been secured by the X-ray crystal structure of calix[4]arene 10 having only one equatorial carboxamide moiety. The use of this novel class of methylene bridge-functionalized calix[4]arenes is illustrated by the formation of bis--lactone 19, while the enhanced acidity of the remaining hydroxyl groups, owing to the presence of axial carboxamide groups at the methine bridges, followed from the easy propylation of bisrearranged calix[4]arene 7.

There is a real need for novel anticancer agents for chemotherapy. In this regard, lignans are an extremely important class of compounds. However, few currently have applications in chemotherapy due to their severe toxicity [1]. Judging by reported applications, etoposide is the most potent lignan known in chemotherapy. It is primarily used in combination chemotherapies, for example chemotherapeutic cycles or pretreatments [2–4]. Often it is applied to treat tumour cells that have developed resistance to previously used chemotherapeutic agents [4,5]. Etoposide is still limited in its applications and common problems found in chemotherapy such as multidrug resistance (MDR) and toxicity problems are also apparent [1,5]. Therefore, the search for novel (lignan) cytostatics continues. This review covers sixteen patents showing some strategies which could potentially enlarge the scope of the use of lignans in chemotherapy.

The bioconversion of the lignan desoxypodophyllotoxin by cell suspensions of Linum flavum and of Podophyllum hexandrum was investigated. The apolar substrate could be easily dissolved in the culture medium at a concentration of 2 mM by complexation with dimethyl-β-cyclodextrin. Growth parameters of the cell suspensions were not affected by either the addition of cyclodextrin itself, or when cyclodextrin-complexed desoxypodophyllotoxin was present in the medium. The complexed lignan disappeared from the medium within 7 days for both cell cultures. Cellularly only small amounts of desoxypodophyllotoxin were found. After feeding of desoxypodophyllotoxin, the cell culture of L. flavum accumulated 5-methoxypodophyllotoxin and 5-methoxypodophyllotoxin-β-D-glucoside. After 7 days a total maximal content of 2.38% on a dry weight basis of 5-methoxypodophyllotoxin was formed. corresponding with 249 mg l-1 suspension. The highest bioconversion percentage of 52.3% was found at day 14. The desoxypodophyllotoxin-fed culture of P. hexandrum accumulated podophyllotoxin and its β-D-glucoside with a maximal content of 2.87% on a dry weight basis after 9 days, corresponding with 192 mg l-1 suspension. The highest bioconversion percentage of 33.2% was also found at day 9.