Efficient Synthesis of N-Benzyloxycarbonyl-2-aminoalkanesulfonyl Chlorides with Functionalized Side Chains

Abstract

N-Benzyloxycarbonyl (Cbz)-protected 2-aminoalkanesulfonyl chlorides are useful building blocks for the synthesis of sulfonopeptides, which are receptor ligands and enzyme inhibitors, and are prepared by the coupling reaction of N-protected aminoalkanesulfonyl chlorides with amino acid or peptide esters. Various N-Cbz-protected 2-aminoalkanesulfonyl chlorides with functionalized side chains were synthesized through the radical addition of different xanthates to benzyl N-allylcarbamate and subsequent oxidative chlorination with tert-butyl hypochlorite under neutral conditions. A mechanism for the oxidative chlorination is proposed. This is a useful and convenient strategy for the synthesis of N-Cbz-protected 2-aminoalkanesulfonyl chlorides with diverse functionalized side-chains.

Key words

oxidative chlorination - radical reaction - sulfonyl chlorides - xanthate - aminoalkanesulfonyl chloride

• References

• 1 Xu JX. Chin. J. Org. Chem. 2003; 23: 1
• 2a Monnee MC. F, Marijne MF, Brouwer AJ, Liskamp RM. J. Tetrahedron Lett. 2000; 41: 7991
• 2b He FD, Meng FH, Song XQ, Hu WX, Xu JX. Org. Lett. 2009; 11: 3922
• 3 Carson KG, Schwender CF, Shroff HN, Cochran NA, Gallant DL, Briskin JM. Bioorg. Med. Chem. Lett. 1997; 7: 711
• 4 Moree WJ, van der Marel GA, Liskamp RM. J. Tetrahedron Lett. 1991; 32: 409
• 5 Humljan J, Kotnik M, Boniface A, Solmajer T, Urleb U, Blanot D, Gobec S. Tetrahedron 2006; 62: 10980
• 6a Kakaei S, Xu JX. Tetrahedron 2013; 69: 9068
• 6b Vertesaljai P, Biswas S, Lebedyeva I, Broggi E, Asiri AM, Katritzky AR. J. Org. Chem. 2014; 79: 2688
• 7a Marchand-Brynaert J, Bouchet M, Touillaux R, Beauve C, Fastrez J. Tetrahedron 1996; 52: 5591
• 7b Giordano C, Masi A, Pizzini A, Sansone A, Consalvi V, Chiaraluce R, Lucente G. Eur. J. Med. Chem. 2009; 44: 179
• 7c Brouwer AJ, Ceylan T, Jonker AM, van der Linden T, Liskamp RM. J. Bioorg. Med. Chem. 2011; 19: 2397
• 7d Uraguchi D, Kinoshita N, Nakashima D, Ooi T. Chem. Sci. 2012; 3: 3161
• 8 Meng FH, Chen N, Xu JX. Sci. China Chem. 2012; 55: 2548
• 9a Gennari C, Ceccarelli S, Piarulli U, Montalbetti CA. G. N, Jackson RF. W. J. Org. Chem. 1998; 63: 5312
• 9b van Ameijde J, Liskamp RM. J. Tetrahedron Lett. 2000; 41: 1103
• 9c Giordano C, Sansone A, Masi A, Lucente G, Punzi P, Mollica A, Pinnen F, Feliciani F, Cacciatore I, Davis P, Lai J, Ma SW, Porreca F, Hruby V. Eur. J. Med. Chem. 2010; 45: 4594
• 10 Chen ZL, Demuth TP. Jr, Wireko FC. Bioorg. Med. Chem. Lett. 2001; 11: 2111
• 11 Bischofberger N, Waldmann H, Saito T, Simon ES, Lees W, Bednarski MD, Whitesides GM. J. Org. Chem. 1988; 53: 3457
• 12a Bischoff L, David C, Roques BP, Zaluski MC. F. J. Org. Chem. 1999; 64: 1420
• 12b Lowik DW. P. M, Liskamp RM. J. Eur. J. Org. Chem. 2000; 1219

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• 13a Quiclet-Sire B, Zard SZ. Synlett 2016; 27: 680
• 13b Debien L, Quiclet-Sire B, Zard SZ. Acc. Chem. Res. 2015; 48: 1237
• 13c Quiclet-Sire B, Zard SZ. Chem. Eur. J. 2006; 12: 6002
• 14a Yang ZH, Xu JX. Synthesis 2013; 45: 1675
• 14b Yang ZH, Xu JX. Org. Synth. 2014; 91: 116
• 15 Prakash GK. S, Mathew T, Panja C, Olah GA. J. Org. Chem. 2007; 72: 5847
• 16a Bahrami K, Khodaei MM, Soheilizad M. J. Org. Chem. 2009; 74: 9287
• 16b Bahrami K, Khodaei MM, Soheilizad M. Synlett 2009; 2773
• 17a Yang ZH, Zheng YP, Xu JX. Synlett 2013; 24: 2165
• 17b Yang ZH, Zhou BN, Xu JX. Synthesis 2014; 46: 225
• 18a Xu CX, Xu JX. Amino Acids 2011; 41: 195
• 18b Chen N, Xu JX. Tetrahedron 2012; 68: 2513
• 19a Ma YH, Xu JX. Synthesis 2012; 44: 2225
• 19b Nai YF, Xu JX. Helv. Chim. Acta 2013; 96: 1355
• 20a Douglass IB, Johnson TB. J. Am. Chem. Soc. 1938; 60: 1486
• 20b Douglass IB, Osborne CE. J. Am. Chem. Soc. 1953; 75: 4582
• 21 Kakaei S, Chen N, Xu JX. Tetrahedron 2013; 69: 302
• 22 Joyard Y, Papamicaël C, Bohn P, Bischoff L. Org. Lett. 2013; 15: 2294