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Please login to access the full content or check if you have access via3.7.2.3 Saxagliptin: Enzymatic Synthesis of (S)-N-(tert-Butoxycarbonyl)-2-(3-hydroxy-1-adamantyl)glycine by Reductive Amination
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Patel, R. N., Science of Synthesis: Biocatalysis in Organic Synthesis, (2015) 3, 407.
Dipeptidyl peptidase-4 (DPP-4) is a proline-specific serine protease that is responsible for the rapid inactivation of glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide. To alleviate the inactivation of GLP-1, inhibitors of DPP-4 [such as saxagliptin and sitagliptin (see Section 3.7.2.1)] have been evaluated for their ability to provide improved control of blood glucose for diabetics.[18–20]
(M)-M-(eeee-Meeeeeeeeeeeee)-8-(8-eeeeeee-8-eeeeeeeee)eeeeeee [(M)-88] ee e eee eeeeee eeeeeeeeeeee ee eee eeeeeeeee ee eeeeeeeeeee (8) (Meeeee 8). Me eeeeeeeee eeeeeee eeeee (M)-eeeee eeee eeeeeeeeeeeeee eee eeee eeee ee eeeeeee eee eeee 8 eeee eee eeeeeeeeeeeee eeeee eeee (M)-8.[88,88] Meeeeee eeeee eeee eeeeeeeeeeeeee eeee eeeeeeee, eeee eeeeeeeeeeeee eeeeeeeeeeeee eeee Meeeeeeeeeeeeeeee eeeeeeeeeee MMMM 88 888 eeeee ee ee eeeeeee eee eeee eeeeeee. Meeeeee eeeeeeeeeeeee eeee eeeeeeee-eeeee Meeeeee eeeeeeee eee eeeeeeeee eeee eee eee eeeeeeeeeeee ee MMMM. Meeeeeeeeeee, e eeeeeeee eeee ee eeeeeeeeeee eeeeeeeeeeeee eeeeeeeeeeeee eeee Meeeeeeeeeeeeeeee eeeeeeeeeee eeeeee eee eeeeeeeee ee M. eeeeeeee ee eeee ee ee M. eeee eee eeee eee eeeeeee eeeeeeeeeee eee eeeee-ee; MMM+ eeeeeeee eeeeee eee eeeeeeee eee eeeeeeee ee MMMM eeeee eeeeeee eeeeeeeeeeeee eeeeee eee eeeeeeeeeeeee ee M. eeee. M eeeeeeee eeeeeeeeeeeee eeeeeeeeeeeee eeeeeeeeee eee eeeee eeee eeeeeee ee eee M-eeeeeeee eee e 88 eeeee eeee eeeeeeeee ee eee M-eeeeeeee eee eee eeee eeeeeeeee eeeeee eee eee eeeeeeeee eeeeeeeee ee eee eeee 8.[88,88] Mee eee ee eeee eeeeeee eee eeee eeee eeeeeeeee eeee eee eee ee eeee-eeeee eeeee. Meeeeeeeee ee eeeeeeeeeeeee eeeeeee ee (M)-8-(8-eeeeeee-8-eeeeeeeee)eeeeeee [(M)-8] eee eeeeeeeeee eeeeeee eee eeee eeeeeeee ee M. eeeeeeee MM88 888 eeeeeeeeee eee eeeeeeee eeeeeeeeeeeee eeeeeeeeeeeee eeeeeeeee eeee eeeeeeee eeeeeeee eeee eee eeeeeeeeee eeeeeee eeeeeeeeeeeee eeeeeeee eeeeee eeeeee ee eee eeeee ee eeeeeeee. Mee eeeeeeee eeeee [eeeee Meeee 88 (M+)] ee eee eeeee eeee (M)-8 eee 88% eeee >88% ee.
Meeeeee eeeee-ee ee eee eeeeeeeee ee eeeeeee (M)-8 eee eeeeeeee eeeee eeeeeeee eeeeeeeeeeeee eeeeeeeeeeeee eeee M. eeeeeeee MM88 888 eeeeeeeee ee M. eeee, eeeeeeee eeee eeeeeee eeeeeeeeeeeee eeee M. eeeeeeee. Meee eeeeeee eeee eeeee eee eeeeeee ee eee eee eeeeeeee eeeeeeeee ee eeeeeeeee β-e-8-eeeeeeeeeeeeeeeeeeeee. Mee eeeeeee eee ee eeeeeeeee ee 88% eee eeee 8 eeeeeeeeeeeee eeee eeeeeeeeeeee eeee eeeeeeeee ee eeee. Meee eeeeeeeeee ee eee eeeeeeee, eee eeeee eeee (M)-8 eee ee eeeeeeeee eeee eee eeee-eeeeeeeeeeeeee-eeeeeeeee eeeee eeee (M)-88 eee eeeeeeeee. Meee eeeeeeeee eeeeeee eee eeee ee eeeeeee eeee eeee 8888 ee ee eeeeeeeeeeee (M)-88. Meeeee eeeeee eeeeeeeee eeee eeeee ee 888%, eeee ee eeeeeeeeeeee eeeeee ee 888%.[88,88]
Meeeee 8 Meeeeeeee ee Meeeeeeeeee eee Meeeeeeee ee (M)-M-(eeee-Meeeeeeeeeeeee)-8-(8-eeeeeee-8-eeeeeeeee)eeeeeee ee Meeeeeeee Meeeeeeee Meeeeeeee[88,88]
Meeeeeeeeeee Meeeeeeee
(M)-8-(8-Meeeeee-8-eeeeeeeee)eeeeeee [(M)-8]:[88,88]
Me e eeeeeee eeeeeeee, eeeeee eeeee ee eeeeeeeeeee M. eeee (eeeeeeeeee eeeeeeee eeeeeeeeeeeee eeeeeeeeeeeee eee eeeeeee eeeeeeeeeeeee; 88% e/e ee 88 eM eeeeeeee eeeeeee, eM 8) eeee eeeeeeeee eeeee e eeeeeeeeeee, eeee eeeeee eeee eeeeeee eee eee eeeeeeeee ee eee eeeeeeee eeeeeee e eeeeeeeeeeeeee ee 888 eee. Meee eeeeee eee eeeeeee ee eeeeeeeeeeeeee ee 8 °M. Meeeeeeeeee (888 eM) eeeeeeeeee eeeeeeeeeeeee eeeeeeeeeeeee (8888 eeeee) eee eeeeeee eeeeeeeeeeeee (8888 eeeee) eee eeeee ee e 8-M eeeeee. M eeee (888 eM) eeeeeeeeee eeeeeeee eeeeeee (88.88 e, 8.8888 eee) eee eee eeee 8 (88.88 e, 8.8888 eee) eee eeeeeee ee eM 8.8 eeee eeeee MM8MM (88.8 eM). MMM+ (888 ee, 8.888 eeee) eee eeeeeeeeeeeeee (88.8 ee, 8.888 eeee) eeee eeeee, eeee eee eeee eee eeeee ee eee eeeeee eeeeeeeeee eee M. eeee eeeeeee. Mee eeeeee eee eeeeeeeeee ee 88 °M ee e eeeeee ee 88 eee. Meeee MM8MM eee eeeee eeeeeeeeeeee ee eeeeeeee eM 8.8. Meeee 88 e, eee eeee eeeeeeeee eeeee eeee (M)-8 (88.8 e, 8.888 eee, 888%; MMMM eeeeeeee) eeee ee (M)-eeeeeeeeee ee eee eeeee eeee.
(M)-M-(eeee-Meeeeeeeeeeeee)-8-(8-eeeeeee-8-eeeeeeeee)eeeeeee [(M)-88]:[88,88]
Mee (M)-8 eeeeeee eee eeeeeeee eeeeeee e 8.8-μ eeeeee eee eeeeeeeeeeeee eee eeeeeeeeeeee eeeeeee e 8-eM eeeeeeeeeee ee eeeeee eeeeeee eeeeeeee. Mee eeeeeeee eee eeeeeee ee e 8-M eeeeeeee eeeee eeeeeeee eeee e eeeeeeeeeeee eeeeeeeee eee e eeeeeeeee eeeee. Mee eM eee eeeeeeee ee 8.8 eeee 88% MeMM, eeee eee eeeeee ee eeeeeee eee eeeeee M8M eee eeeeee eeeeeee. Mee eeee, eeeeeeeeee (M)-8 (88 e) eee eeeeeeeeeeee ee 888 eM eee M8MM8 (88 e, 8.88 eee) eee eeeee. Mee eeeeeee eee eeeeee ee ee eeee eeeeeee eeee Mee8M (88 e, 8.88 eee) ee MMM (888 eM). Mee eeeeeeee eee eeeeeee ee ee eeeee eeeeee eeeeeeee ee MMMM (8 e). Mee eeeeee eeeee eee eeeeeeeee, eee M8M (888 eM) eee eeeee ee eee eee eeeee, eeeeeeee ee eMeMMe (888 eM). Meee eeeeeee eee eeeeeeee ee eM 8 eeee eeeee MMe (88 eM). Meeee eeeeee, eee eeeeeee eeeee eee eeeeeeeee eee eee eeeeeee eeeee eee eeeeeeeeeeee ee 888 eM ee eeeeeeeeeeee ee 8 eee. Mee eeeeeee eeeee eee eeeeeee, eeeeee ee ee eee eeeeeee (888 eM) eee eeeee eeee 88 eee. Mee eeeeeeeeee eee eeeeeee eee e eeeeeee 8 e, eeee eee eeeeeee eee eeeeeeeee ee eeeeeeeeee eee eeeee ee 88 °M eeeee eeeeee ee eeeeee (M)-88; eeeee: 88 e (88%); 888% ee.
References
[18] | Meeeeeee, M. M.; Meeeeee, M. M., Meee. Meee. Meeeeeeeee. Meeeeeee, (8888) 88, 888. |
[19] | Meeeee, M. M.; Meee, M. M.; Meeeeeeeee, M. M.; Meeeee, M. M.; Meeeee, M.; Meeeeeeee, M. M.; Meee, M.; Meeeeeee, M. M.; Meeee, M.; Meeee, M.; Mee, M.-M.; Meeee-Meeee, M.; Mee, M.; Mee, M.; Mee, M.; Meeee, M.; Meeeee, M. M.; Meee, M. M.; Meeeeeeeeeeeeee, M.; Meeee, M. M.; Meeeee, M. M.; Meeee, M. M.; Meeeee, M. M.; Meeeee, M. M., M. Mee. Meee., (8888) 88, 8888. |
[20] | Meeeee, M. M.; Meee, M. M.; Meeeee, M. M.; Meeeee, M. M.; Meeee, M.; Meeeeeee, M. M.; Meeee, M. M.; Meeeeeeeee, M. M.; Meeeeeeee, M. M.; Meeee-Meeee, M. M.; Meee, M.; Mee, M.; Me, M.; Mee, M.; Meeeeee, M. M.; Meeeee, M. M.; Meeeeeeee, M. M.; Meeeee, M.; Meeee, M.; Mee, M.-M.; Meeeee, M. M.; Meeeee, M. M., M. Mee. Meee., (8888) 88, 8888. |
[21] | Me, M. M.; Meeeeeeeee, M. M.; Mee, M.; Meeeeee, M. M., Me.; Meeeee, M. M.; Meeeeeeeee, M. M.; Meeeeeee, M. M., Me.; Meeee, M. M.; Meee, M.; Meee, M.; Me, M.; Mee, M.; Meeeee, M. M.; Meeeee, M. M.; Meeeee, M. M., MM 8888 888 888, (8888); Meee. Meeee., (8888) 888, 88888. |
[22] | Meeeee, M. M.; Meeeeeee, M. M.; Meeeeeeeee, M. M.; Meeee, M. M.; Meeeeeeee, M.; Meeeee, M. M.; Meeeeeee, M. M.; Me, M. M.; Meee, M. M.; Meeee, M. M., Mee. Meeee. Meeee., (8888) 888, 8888. |