The Asymmetric Synthesis of tert-Butyl (4R,6R)-6-(2-aminoethyl)-2,2-dimethyl-1,3- dioxane-4-acetate: An Important Intermediate of HMG-CoA Reductase Inhibitor

International Journal of Applied Chemistry

© 2020 by SSRG - IJAC Journal

Volume 7 Issue 3

Year of Publication : 2020

Authors : Yoshifumi Yuasa

10.14445/23939133/IJAC-V7I3P104

How to Cite?

Yoshifumi Yuasa, "The Asymmetric Synthesis of tert-Butyl (4R,6R)-6-(2-aminoethyl)-2,2-dimethyl-1,3- dioxane-4-acetate: An Important Intermediate of HMG-CoA Reductase Inhibitor," SSRG International Journal of Applied Chemistry, vol. 7,  no. 3, pp. 21-24, 2020. Crossref, https://doi.org/10.14445/23939133/IJAC-V7I3P104

Abstract:

tert-Butyl (4R,6R)-6-(2-aminoethyl)-2,2-dimethyl-1,3-dioxane-4-acetate 1, which is the important intermediate for atorvastatin [Statin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)], could be prepared from N-carbobenzyloxy-B-alanine 3 through the asymmetric hydrogenation using the Ru-BINAP complex catalyst as the key step in 8 steps.

Keywords:

(4R,6R)-t-Butyl-6-(2-aminoethyl)-2,2-dimethyl-1,3-dioxane-4-acetate, N-Carbobenzyloxyalanine, HMG-CoA reductase inhibitor, Atorvastatin, Asymmetric hydrogenation, Ru-BINAP catalyst.

References:

[1] For a recent example, there are many reports. See P. Hoyos, V. Pace, and A. R. Alcantara. "Biocatalyed Synthesis of Statins: A Sustainable Strategy for the Preparation of Valuable Drugs" Catalysts, 2019, 9, pp. 260-292, and reference cited therein.
[2] a) P. L. Brower, D. E. Bulter, C. F. Deering, T. V. L.A. Millar, T. N. Nanninga, B. D. Rotha. "The synthesis of (4R-cis)-1,1-dimethyl ethyl 6-cyanomethyl-2,2-dimethyl-1,3-dioxane-4-acetate, a key intermediate for the preparation of CI-981, a highly potent, tissueselective inhibitor of HMG-CoA reductase" Tetrahedron Lett., 1992, 33, pp. 2279-2282. b) D.E.Butler, T. V. L, A. Millar, and T. N. Nanninga. "Process for the synthesis of (5R)-1,1-dimethyl ethyl-6-cyano-5-hydroxy-3-oxohexanoate" US Patent 5155251, 1992. c) N. J. Turner, E. O'Reilly. "Biocatalytic retrosynthesis" Nat. Chem. Biol., 2013, 9, pp. 285-288.
[3] a) K. E. Koenig. In Asymmetric synthesis. Vol. 5. Edited by J. D. Morrison. Academic Press, New York. 1985. p.71. b) R. Noyori, and H. Takaya. "BINAP: An Efficient Chiral Element for Asymmetric Catalysis" Acc. Chem. Res., 1990, 23, pp. 345-350. c) H. Takaya and R. Noyori. In Comprehensive organic synthesis. Vol. 8. Edited by B. M. Trost and I. Fleming. Pergamon Press, Oxford. Chap. 3.2. 1991, pp.433-469. d) R. Noyori. "Asymmetric Catalysis by Chiral Metal Complexes" CHEMTECH, 1992, pp. 360-367. e) H. Takaya, T. Ohta, R. Noyori. "In Asymmetric Catalytic Synthesis," Edited by Ojima, I. VCH Publishers, New York. 1993. f) R. Noyori. In Asymmetric catalysis in organic synthesis. John Wiley & Sons, Inc., New York. 1994. Chap. 2. g) R. Noyori. "Organometallic ways for the multiplication of chirality" Tetrahedron 1994, 50, pp. 4259-4292.
[4] W. Tang, and X, Zhang. "New Chiral Phosphorus Ligands for Enantioselective Hydrogenation" Chem. Rev., 2003, 103, pp. 3029-3070, and reference cited therein.
[5] M. Kitamura, T. Ohkuma, H. Takaya, and R. Noyori. "A practical asymmetric synthesis of carnitine" Tetrahedron Lett., 1988, 29, pp. 1555-1556.
[6] a) Y. Yuasa. "The practical, efficient, diastereoselective synthesis of (3R,1'S)-3- [(1'-N-methylamino)ethyl]-pyrroli-dine: A chiral side chain unit for quinolone type anti-fungus agents" Indian J. Chem., 2018, 58B, pp. 1189-1193. b) Y. Yuasa. "The Synthesis of Optically-Active erythro-Methylphenidate by Diastereoselective Hydrogenation Using Ru-BINAP Complex Catalyst" SSGR Int. J. Appl. Chem., 2020, 7, pp. 70-74.
[7] T. Ikariya, Y. Ishii, H. Kawano, T. Arai, S. Yoshikawa, and S. Akutagawa. "Synthesis of novel chiral ruthenium complexes of 2,2′- bis(diphenylphosphino)-1,1′-binaphthyl and their use as asymmetric catalysts" J. Chem. Soc., Chem. Commun., 1985, pp. 922-924.
[8] a) D. W. Brooks, L. D.-L. Lu and S. Masamune. "C-Acylation under virtually neutral conditions" Angew. Chem. Int. Ed. Engl., 1970, 18, pp. 72-74. b) T. Nishi, K. Higashi, T. Soga, M. Takemura, and M. Sato. "Synthesis and Antibacterial Activity of New 2-Substituted Penems. II" The Journal of Antibiotics, 1994, 47, pp. 357-369.
[9] T. Ohta, Y. Tonomura, K. Nozaki, H. Takaya, and K. Mashita. "An Anionic Dinuclear BINAP-Ruthenium (II) Complex: Crystal Structure of [NH2Et2][{RuCl((R)-p-MeO- BINAP)}2(μ-Cl)3] and Its Use in Asymmetric Hydrogenation" Organiometallics, 1996, 15, pp. 1521-1523.
[10] L. B. Kelvin, D. E. Bulter, C. F. Deering, K. E. Mennen, A. Millar, T. N. Nanninga, C. W. Palmer, and B. D. Rotha. "The Convergent Synthesis of CI-981, an Optically Active, Highly Potent, Tissue Selective Inhibitor of HMG-CoA Reductase" Tetrahedron Lett., 1992, 33, pp. 2283-2284.