Synthesis of a Potential Precursor (Northern Fragment) for the Cyclic Depsipeptides Vioprolides A and C

Abstract

The synthesis of a potential northern fragment for the cyclic depsipeptides vioprolide A and vioprolide C is accomplished. The prepared compound is a pentapeptide and displays the non-canonical amino acid dehydrobutyrine (Dhb) at its C-terminal end. The central position is taken by another non-canonical amino acid, (2S,4R)-4-methylazetidine carboxylic acid (Maz). A route to enantiopure N-Boc-protected Maz (N-Boc-Maz) is developed from l-pyroglutamic acid, and this building block is taken into thiopeptide formation at its C-terminal end by successively coupling serine and threonine fragments. The C-terminal threonine is dehydrated to Dhb before attaching a d-Leu-Ala dipeptide to the N-terminal site of Maz. Several intermediates are directly telescoped into the next reaction step. Starting from N-Boc-Maz, the assembly of the pentapeptide is complete in eight steps with an overall yield of 16%.

Key words

amino acids - azetidine - ring contraction - peptides - stereoselective synthesis

• References

• 1 Schummer D, Forche E, Wray V, Domke T, Reichenbach H, Höfle G. Liebigs Ann. 1996; 971
• 2 Kirsch VC, Orgler C, Braig S, Jeremias I, Auerbach D, Müller R, Vollmar AM, Sieber SA. Angew. Chem. Int. Ed. 2020; 59: 1595
• 3a Burgers LD, Luong B, Li Y, Fabritius MP, Michalakis S, Reichel CA, Müller R, Fürst R. Biomed. Pharmacother. 2021; 144: 112255
• 3b Burgers LD, Li Y, Michalakis S, Ciurus S, Zahler S, Müller R, Fürst R. Biomed. Pharmacother. 2022; 152: 113174
• 4 Yan F, Auerbach D, Chai Y, Keller L, Tu Q, Hüttel S, Glemser A, Grab HA, Bach T, Zhang Y, Müller R. Angew. Chem. Int. Ed. 2018; 57: 8754
• 5 Grab HA, Kirsch VC, Sieber SA, Bach T. Angew. Chem. Int. Ed. 2020; 59: 12357

For synthetic studies on the vioprolides by other groups, see:
• 6a Chopin N, Couty F, Evano G. Lett. Org. Chem. 2010; 7: 353
• 6b Liu H, Thomas EJ. Tetrahedron Lett. 2013; 54: 3150
• 6c Butler E, Florentino L, Cornut D, Gomez-Campillos G, Liu H, Regan AC, Thomas EJ. Org. Biomol. Chem. 2018; 16: 6935
• 7 Kern N, Felten A.-S, Weibel J.-M, Pale P, Blanc A. Org. Lett. 2014; 16: 6104
• 8a Wuts PG. M. Greene’s Protective Groups in Organic Synthesis, 5th ed. John Wiley & Sons; Hoboken: 2014: 1104-1106
• 8b Kan T, Fukuyama T. Chem. Commun. 2004; 353
• 9 Otsuka M, Masuda T, Haupt A, Ohno M, Shiraki T, Sugiura Y, Maeda K. J. Am. Chem. Soc. 1990; 112: 838
• 10 Provot O, Celerier JP, Petit H, Lhommet G. J. Org. Chem. 1992; 57: 2163
• 11 Mandal PK, Birtwistle JS, McMurray JS. J. Org. Chem. 2014; 79: 8422
• 12a Yokosaka T, Kanehira T, Nakayama H, Nemoto T, Hamada Y. Tetrahedron 2014; 70: 2151
• 12b Nakamura H, Tsukano C, Yoshida T, Yasui M, Yokouchi S, Kobayashi Y, Igarashi M, Takemoto Y. J. Am. Chem. Soc. 2019; 141: 8527
• 13a Minehira D, Takahara S, Adachi I, Toyooka N. Tetrahedron Lett. 2014; 55: 5778
• 13b Popp TA, Uhl E, Ong DN, Dittrich S, Bracher F. Tetrahedron 2016; 72: 1668
• 14a Narayan RS, VanNieuwenhze MS. Org. Lett. 2005; 7: 2655
• 14b Craig RA, O’Connor NR, Goldberg AF. G. Chem. Eur. J. 2014; 20: 4806
• 15a Nagao Y, Kumagai T, Nagase Y, Tamai S, Inoue Y, Shiro M. J. Org. Chem. 1992; 57: 4232
• 15b Eckelbarger JD, Wilmot JT, Gin DY. J. Am. Chem. Soc. 2006; 128: 10370
• 16a Cohen SM, Meyer M, Raymond KN. J. Am. Chem. Soc. 1998; 120: 6277
• 16b Meiresonne T, Mangelinckx S, De Kimpe N. Tetrahedron 2012; 68: 9566
• 17 Shalaby MA, Grote CW, Rapoport H. J. Org. Chem. 1996; 61: 9045
• 18 Steinmetz H, Li J, Fu C, Zaburannyi N, Kunze B, Harmrolfs K, Schmitt V, Herrmann J, Reichenbach H, Höfle G, Kalesse M, Müller R. Angew. Chem. Int. Ed. 2016; 55: 10113
• 19 Ding L, Ma S, Lou H, Sun L, Ji M. Molecules 2015; 20: 21501
• 20 Deeley J, Bertram A, Pattenden G. Org. Biomol. Chem. 2008; 6: 1994
• 21 Crescenza A, Botta M, Corelli F, Santini A, Tafi A. J. Org. Chem. 1999; 64: 3019
• 22 Wen S, Packham G, Ganesan A. J. Org. Chem. 2008; 73: 9353
• 23 Hjelmgaard T, Sotofte I, Tanner D. J. Org. Chem. 2005; 70: 5688
• 24 McKeever B, Pattenden G. Tetrahedron 2003; 59: 2701