| COMPANY COUNTRY | USA |
| CLASSIFICATION | CommPat |
| SYNTHESIS |
The original synthesis of the drug candidate, a 5H-2,3-benzo diazepine denoted LY300164, contained several problema tic steps. For example, the synthesis required a large vol. of solvent, generated a large amount of Cr waste, & contained an asymmetric reduction step that was not very efficient. By completely revamping the synthetic strategy, Co.'s resear chers responsible for its development have eliminated the use of some 34,000 L of solvent & the generation of about 300 kg Cr waste for every 100 kg of LY300164 produced. Moreover, only three of the six intermediates generated are isolated, limiting worker exposure & decreasing processing costs. The new synthesis is more efficient as well; the overall yield climbed from 16 to 55 %. The synthesis begins with the biocatalytic reduction of a ketone to an optically pure alc. The yeast Zygosaccharomy ces rouxii exhibits good reductase activity, but it succumbs to high concn of the substrate or prodt. To circumvent this problem the researchers use a novel three-phase reaction design. The starting ketone is added to an aq. slurry contg a solid polymeric resin, buffer, & glucose, with most of the ketone adsorbing to the resin. As the ketone diffuses into soln., it is reduced by the yeast, & the alc. prodt adsorbs to the resin, which is then collected by filtration. All the organic reaction comp. are removed from the aq waste stream, permitting the use of conventional wastewater treat. A later step in the original synthesis called for using CrO3 a possible carcinogen, to oxidize a C atom in the isochroman intermediate. By changing the synthesis so that the oxidation can be accomplished using air, NaOH & DMSO, the researchers totally eliminated the generation of Cr waste |
| UPDATE | 07.99 |
| INVENTOR | This data is not available for free |
| LITERATURE REF. | This data is not available for free |
| PATENT ASSIGNEE | This data is not available for free |
| PATENT PHOTOCOPY | Available on request |
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