Chiral myo-inositol derivatives play key roles in cell-signaling processes.[1] Despite the relevance of these compounds, few syntheses rely on enantioselective catalytic reactions.[2] Even fewer reports describe the use of desymmetrization of myo-inositol derivatives.[3] In fact, most routes involve resolution by derivatization.
We have previously found that TL-IM and RM-IM lipases, in vinyl acetate as solvent, are able to desymmetrize myo-inositol derivative 1, a potential precursor of different bioactive inositol phosphates, leading to chiral compound 2 in high ee (Scheme 1).[4]
Herein, we will disclose our results on the effects of solvents on conversion and rate in the TL-IM lipase-catalyzed synthesis of chiral compound 2 (Table 1). Both EtOAc and, more markedly, TBME increased conversions of 1 to 2 and rates, while maintaining the high ee.
We shall also report on the determination of acetate 2´s configuration (as L-6-O-Ac) through conversion to a chemical reference.
References: 1. (a) H. Ivanova, T. Vervliet, L. Missiaen, J. B. Parys, H. De Smedt, G. Bultynck. Biochem. Bioph. Acta Mol. Cell Res. 2014, 1843, 2164-2183; (b) C. W. Distelhorst, M. D. Bootman, Cell Calcium, 2011, 50, 234-241. (c) T. B. Reynolds, Microbiol., 2009, 155, 1386-1396; (d) A. R. Alcázar-Román, S. R. Wente, Chromosoma 2008, 117, 1-13. 2. (a) B. Kilbas, M. Balci, Tetrahedron 2011, 67, 2355–2389. (b) B. V. L. Potter, D. Lampe, Angew. Chem. Int. Ed. Eng. 1995, 34, 1933–1972. 3. For a review, see: E. A. Manoel, K. C. Pais, A. G. Cunha, A.B. C. Simas, M. A. Z. Coelho, D. M. G. Freire, Org. Proc. Res. Dev. 2012, 16, 1378–1384. 4. (a) K. C. Pais, D. Sc. Thesis, UFRJ, 2014. A. B. C. Simas et al., submitted.