Mitotane (o,p'-DDD) can be used for the treatment of various adrenocortical diseases such as Cushing's syndrome, but the usual doses of 6-8 g per day are often associated with severe adverse effects. This paper reports the results of much lower doses of o,p'-DDD (0.5-2 g per day) in two patients with Cushing's disease over periods of 8 and 5 years, respectively, under concomitant monitoring of the plasma levels of the parent drug and its major metabolite, o,p'-DDE. It became apparent that o,p'-DDD and o,p'-DDE have a strong tendency to accumulate in the body due to their high lipophilicity. As a consequence, changes in dose regimens had long lag times before they were reflected in plasma levels and once an increase or decrease had started one had to be careful not to cause overshoot. Steady state plasma levels of o,p'-DDD between 5-10 micrograms/ml appeared sufficient to induce and to maintain remission of the disease, which was accompanied with normal cortisol levels in plasma and urine. DDD-levels below 5 micrograms/ml for several weeks may lead to relapses, whereas DDD-levels over 10 micrograms/ml gave rise to side effects. On the other hand, o,p'-DDE seemed inactive at levels up to 4 micrograms/ml in plasma.
Stereoselective synthesis of glycosides (glucosides, galactosides, mannosides, and xylosides) is reported using long-chain alcohols with 0-4 ethoxy spacers as potential anchored cryoprotectors.Glycolipids are one of the basic constituents of biological membranes besides phospholipids. The sugar residues in these membranes on the cell surface are playing an important role in the biological response. With this goal we have tried to analyze the influence of different sugar units on the physicochemical properties of phospholipid systems, especially hydration"] and the behavior of lipid systems during water removal under freezing condition and desiccation (lyophilization)[21 and also on the interaction between phospholipidglycolipid systems with cells131. Glycosides of long-
R'OR chain alcohols are of our special interest because of the homogeneity of their mixture with phosphatidyl choline to an unlimited extent, also resulting to the formation of lipid vesicles in these mixturesr41. For these investigations we required some glycosides of different sugars with long-chain alkyl groups and with spacers containing a different number of ethyleneoxy groups between sugar and alkyl moiety.Although a number of methods [5] are known in the literature for glycosidation, none of the three existing main methods, namely the Koenigs-Knorr method, the Lewis acidcatalyzed process and the synthesis using a phase-transfer catalyst (PTC) provides good stereoselectivity in good overall yield, particularly with long-chain alcohols because of their low reactivity. Especially cis glycosidation is still prob-
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