Optical Resolution via Diastereomeric Salt Formation

Entry (R)-10 equiv. Solvent Yield % Optical purity % ee Resolvabilit/ S 

This chapter represents the outstanding contribuhons of many scienhsts within the Takeda Pharmaceuhcal Company discovery chemists, process chemists, ana-lyhcal chemists, and chemical engineers. The authors hereby express their sincere gratitude to many colleagues whose hard work and dedication led to the success of these projects. 

9 a) Sawai, Y. (2008) Process research of peptide mimetic compounds as diabetic drug candidate. Proceedings of The Eighteenth International Conference on Organic Process Research and Development, Montreal, Canada, June 23-26, 2008 (b) Sawai, Y., Yamane, T., Ikeuchi, M., Kawaguchi, S., Yamada, M., and Yamano, M. Org. Process Res. Dev., submitted for publication (c) Sawai, Y., Mizuno, M., Ito, T., Kawakami, J., and Yamano, M. (2009) Tetrahedron, 65, 7122-7128 

11 Welch, C.J., Fleitz, F., Antia, F., Yehl, P., Waters, R., Ikemoto, N., Armstrong, 

16 (a) Kozma, D. (2002) CRC Handbook of Optical Resolutions via Diastereomeric Salt Formation, CRC Press LLC, Boca Raton. 

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Kozma, D. Ed., (2002) CRC handbook of Optical Resolution via Diastereomeric salt Formation, CRC Press, Boca Raton Florida. 

Sakai, K., Saigo, K., Murakami, H., Nohira, H. (1993) Relation between molecular structure and resolvability on optical resolution via diastereomeric salt formation, Symposium on Chiral Compounds (Tokyo), Oct 22. 

Kozma D, editor. CRC LLandbook of optical resolutions via diastereomeric salts formation. Boca Raton (FL) CRC Press 2002. 

A short three-step synthesis has been developed for the -N(Et)2 derivative 291. (—)-N-Boc-0-benzyl (S) tyrosine among 63 optically pure resolving agents was found suitable for a large-scale resolution via diastereomeric salt formation. The (S) configuration was assigned to the (—) form by X-ray of the diastereomeric complex (03JOC7379). 

Quite a few examples of optical resolution via formation of the less soluble diastereomeric salt have been reported in which the species to be resolved and the chiral selector are both complex ions. Thus elucidation of the mode of chiral discrimination between complex cations and anions is an important factor leading to the discovery of new efficient resolving agents. As one of several approaches to this subject, we carried out very simple experiments. 

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