Hoechst’s ether

This encouraging precedent led us to develop new asymmetric syntheses of haiothane (27) and desflurane plus the desflurane analogue "Hoechst s ether" (22). The cornerstone of the second-generation syntheses is stereoselective decarboxylation. In both cases, a chiral halogenated acid derivative was prepared which had the carboxyl group attached directly to the chiral center. Rather than use salt formation and repeated crystallization for resolution of the acids, we chose to form secondary amides and use chromatography for separation of the resulting diastereomers. The diastereomerically enriched amides would then he converted to enantiomerically enriched acids to be used as decarboxylation substrates. 

Using a similar strategy, we also envisioned the asymmetric synthesis of another anesthetic compound, "Hoechst s ether (see Scheme 4). This molecule was first synthesized in racemic form by chemists at Hoechst (24), The mixture of four diastereomers was patented as an anesthetic, but its properties were not desirable enough for it to be brought to market. The situation here is more complicated because there are two chiral centers to deal with in an asymmetric synthesis. To keep things manageable, we decided to control the stereochemistry at only one of the chiral centers. The product in this case would be a pair of diastereomers. If we were successful, we hoped that one or both of the diastereomeric pirs would have improved anesthetic properties vs. the racemate. The first big hurdle was a synthesis of the enantioenriched acid, which turned out to be relatively simple (Scheme 7). 

Scheme 10. Completion of the Synthesis of a Diastereomeric Pair of Hoechst s Ether...

Definition PEG ether of a dimer of glycerin esterified with lauric acid containing avg. ethoxylation value of 10 Uses Emollient, emulsifier in cosmetics Trade Name Synonyms Hoe S 3495 t[Hoechst Celanese/Surf. ] Hostacerin DGL [Clariant/Functional Chems.]... 

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