maury

We have developed a catalytic asymmetric synthesis of (S)-4-ethyl-6,6-(ethylenedioxy)-7,8-dihydro-4-hydroxy-1H-pyrano[3,4-f]indolizine-3,10(4H)dione (5 a), a synthetic intermediate for (20S)-camptothecin analogues. A key step in this synthesis is an asymmetric α-hydroxylation of a lactone with a vinylogous pyridone structure (8 a) by using a guanidine–urea bifunctional organocatalyst. The present oxidation was successfully applied to the synthesis of C20-modified derivatives of (+)-C20-desethylbenzylcamptothecin (13).

Two is better than one! An enantioselective α-hydroxylation of a lactone with a vinylogous pyridone structure has been achieved using a guanidine–urea bifunctional organocatalyst. The hydroxylation product, which is a key synthetic intermediate of (20S)-camptothecin and its analogues, was obtained in 95 % yield with 84 % ee (see scheme; CHP=cumene hydroperoxide).

Back to ‘base'ics: The title reaction of enantioenriched α-ureidonitriles was found to proceed in a highly enantiodivergent manner despite the intermediacy of stereolabile α-nitrile metallocarbanions. Enantiodivergence is dependent upon the base used. For the less basic hexamethyldisilazides (HMDS), deprotonation in which a metal (M) cation is precomplexed with an electrophile is proposed. LDA=lithium diisopropylamide.