Synthesis, Table of Contents Synthesis 2022; 54(08): 2031-2036DOI: 10.1055/a-1695-1095 paper A Convenient On-Site Oxidation Strategy for the N-Hydroxylation of Melanostatin Neuropeptide Using Cope Elimination Authors Ivo E. Sampaio-Dias ∗ Sara C. Silva-Reis Beatriz L. Pires-Lima Xavier Cruz Correia Hugo F. Costa-Almeida Recommend Article Abstract Buy Article(opens in new window) All articles of this category(opens in new window) Abstract Abstract A convenient synthetic protocol for the unprecedented N-hydroxylation of proline residue in Melanostatin (MIF-1) neuropeptide is reported. This methodology is grounded on the incorporation of N-(cyanoethyl)prolyl residue followed by on-site oxidation by Cope elimination with m-chloroperbenzoic acid, exploring the unrecognized dual role of the cyanoethyl group as an effective N-protecting group under peptide synthesis conditions and as a suitable leaving group during the chemoselective on-site N-oxidation. Following this protocol N-hydroxy-MIF-1 is obtained in 78% global yield from N-(cyanoethyl)-l-proline. This synthetic approach opens a new avenue for access to N-hydroxylated Melanostatin analogues with direct application in neurochemistry and Parkinson’s research. Key words Key wordsCope elimination - Melanostatin - Michael addition - MIF-1 - secondary hydroxylamines Full Text References References 1 Sarnowski MP, Del Valle JR. Org. Biomol. Chem. 2020; 18: 3690 2 Ottenheijm HC. J, Herscheid JD. M. Chem. Rev. 1986; 86: 697 3 Afzal A. Bull. Chem. Soc. Jpn. 1974; 47: 1819 4 Nagasawa HT, Kohlhoff JG, Fraser PS, Mikhail AA. J. Med. Chem. 1972; 15: 483 5 Jain R, Singh J, Perlman JH, Gershengorn MC. Bioorg. Med. Chem. 2002; 10: 189 6 da Costa JF, Caamaño O, Fernández F, García-Mera X, Sampaio-Dias IE, Brea JM, Cadavid MI. Eur. J. Med. Chem. 2013; 69: : 146 7 Sampaio-Dias IE, Sousa CA. D, García-Mera X, da Costa JF, Caamaño O, Rodríguez-Borges JE. Org. Biomol. Chem. 2016; 14: 11065 8 Sampaio-Dias IE, Silva-Reis SC, García-Mera X, Brea J, Loza MI, Alves CS, Algarra M, Rodríguez-Borges JE. ACS Chem. Neurosci. 2019; 10: 3690 9 Khan RS, Yu C, Kastin AJ, He Y, Ehrensing RH, Hsuchou H, Stone KP, Pan W. Int. J. Pept. 2010; 53769 10a Verma V, Mann A, Costain W, Pontoriero G, Castellano JM, Skoblenick K, Gupta SK, Pristupa Z, Niznik HB, Johnson RL, Nair VD, Mishra RK. J. Pharmacol. Exp. Ther. 2005; 315: 1228 10b Vartak AP, Skoblenick K, Thomas N, Mishra RK, Johnson RL. J. Med. Chem. 2007; 50: 6725 11a Srivastava LK, Bajwa SB, Johnson RL, Mishra RK. J. Neurochem. 1988; 50: 960 11b Saitton S, Del Tredici AL, Mohell N, Vollinga RC, Boström D, Kihlberg J, Luthman K. J. Med. Chem. 2004; 47: 6595 11c Reed GW, Olson GA, Olson RD. Neurosci. Biobeh. Rev. 1994; 18: 519 12a Birtwistle J, Baldwin D. Br. J. Nurs. 1998; 7: 832 12b Fisher A, Mann A, Verma V, Thomas N, Mishra RK, Johnson RL. J. Med. Chem. 2006; 49: 307 12c Bhagwanth S, Mishra RK, Johnson RL. Beilstein J. Org. Chem. 2013; 9: 204 12d Sampaio-Dias IE, Reis-Mendes A, Costa VM, García-Mera X, Brea J, Loza MI, Pires-Lima BL, Alcoholado C, Algarra M, Rodríguez-Borges JE. J. Med. Chem. 2021; 64: 6209 13 Nemchik A, Badescu V, Phanstiel O. Tetrahedron 2003; 59: 4315 14 Banerjee A, Yamamoto H. Chem. Sci. 2019; 10: 2124 15 Berman AM, Johnson JS. J. Org. Chem. 2006; 71: 219 16a Biloski AJ, Ganem B. Synthesis 1983; 537 16b Milewska MJ, Chimiak A. Synthesis 1990; 233 16c Wang QX, King J, Phanstiel O. J. Org. Chem. 1997; 62: 8104 17 Li W.-R, Yo Y.-C, Lin Y.-S. Tetrahedron 2000; 56: 8867 18 O’Neil IA, Cleator E, Tapolczay DJ. Tetrahedron Lett. 2001; 42: 8247 19 Sousa CA. D, Sampaio-Dias IE, Garcia-Mera X, Lima CF. R. A. C, Rodriguez-Borges JE. Org. Chem. Front. 2016; 3: 1624 20 Sampaio-Dias IE, Rodríguez-Borges JE, Yáñez-Pérez V, Arrasate S, Llorente J, Brea JM, Bediaga H, Viña D, Loza MI, Caamaño O, García-Mera X, González-Díaz H. ACS Chem. Neurosci. 2021; 12: 203 21 Wang T, Danishefsky SJ. J. Am. Chem. Soc. 2012; 134: 13244 22a Mizoguchi T, Shigezane K, Takamura N. Chem. Pharm. Bull. 1970; 18: 1465 22b Valle G, Crisma M, Toniolo C, Yu K.-L, Johnson RL. J. Chem. Soc., Perkin Trans. 2 1989; 83 23 Hruby VJ, Brewster AI, Glasel JA. Proc. Natl. Acad. Sci. U.S.A. 1971; 68: 450 Supplementary Material Supplementary Material Supporting Information (PDF)
