Synthesis of Novel Enantiopure Amino- and Azidopyran Building Blocks and Their Click Reactions to Multivalent Carbohydrate Mimetics

Abstract

The synthesis of three enantiopure 1,2-oxazine-derived azides was optimized and the reductions of these compounds to amino alcohols were studied. As a primary aim of this study, the copper-catalyzed (3+2)-cycloadditions of the azides were investigated, employing a series of alkynes, dialkynes, and trialkynes, which afforded the corresponding mono-, di-, and trivalent triazole derivatives with different rigid and flexible core elements. The expected click products were generally obtained in good to excellent yields when copper iodide was employed in presence of tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]amine (TBTA) as ligand in acetonitrile at room temperature. Several of the products were subjected to exhaustive hydrogenolysis reactions, leading to enantiopure compounds with aminopyran substructures, which can be regarded as carbohydrate mimetics.

Key words

alkynes - azides - click reaction - copper catalysis - (3+2)-cycloaddition - hydrogenolysis - reduction - triazoles

• References

• 1 New address: P. Koóš, Department of Organic Chemistry, Institute of Organic Chemistry, Catalysis and Petrochemistry, Slovak University of Technology, 81137 Bratislava, Slovakia; Georganics Ltd., 81103 Bratislava, Slovakia.

For key publications, see:
• 2a Schade W, Reissig H.-U. Synlett 1999; 632
• 2b Helms M, Schade W, Pulz R, Watanabe T, Al-Harrasi A, Fišera L, Hlobilová I, Zahn G, Reissig H.-U. Eur. J. Org. Chem. 2005; 1003
• 2c Bouché L, Kandziora M, Reissig H.-U. Beilstein J. Org. Chem. 2014; 10: 213
• 3 Al-Harrasi A, Reissig H.-U. Angew. Chem. Int. Ed. 2005; 44: 6227 ; Angew. Chem. 2005, 117, 6383
• 4 Al-Harrasi A, Pfrengle F, Prisyazhnyuk V, Yekta S, Koóš P, Reissig H.-U. Chem. Eur. J. 2009; 15: 11632

For selected reviews, see:
• 5a Koester DC, Holkenbrink A, Werz DB. Synthesis 2010; 3217
• 5b Pfrengle F, Reissig H.-U. Chem. Soc. Rev. 2010; 39: 549
• 5c Bouché L, Reissig H.-U. Pure Appl. Chem. 2012; 84: 23
• 5d Compain P. Synlett 2023; 34: 1866
• 6 For a recent review on multivalency, see: Fasting C, Schalley CA, Weber M, Seitz O, Hecht S, Koksch B, Dernedde J, Graf C, Knapp E.-W, Haag R. Angew. Chem. Int. Ed. 2012; 51: 10472 ; Angew. Chem. 2012, 124, 10622
• 7a Bouché L, Reissig H.-U. Eur. J. Org. Chem. 2014; 3697
• 7b Salta J, Reissig H.-U. Eur. J. Org. Chem. 2020; 4361
• 7c Salta J, Arp FF, Kühne C, Reissig H.-U. Eur. J. Org. Chem. 2020; 7333
• 8a Sakai N, Hida N, Kondo K. Bull. Chem. Soc. Jpn. 1986; 59: 179
• 8b van Berkel SS, Brauch S, Gabriel L, Henze M, Stark S, Vasilev D, Wessjohann LA, Abbas M, Westermann B. Angew. Chem. Int. Ed. 2012; 51: 5343 ; Angew. Chem. 2012, 124, 5437
• 9a Salta J, Dernedde J, Reissig H.-U. Beilstein J. Org. Chem. 2015; 11: 638
• 9b Salta J, Reissig H.-U. Synthesis 2015; 47: 1893

For selected references, see:
• 10a McEver R, Moore K, Cummings R. J. Biol. Chem. 1995; 270: 11025
• 10b Sears P, Wong C.-H. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 12086
• 10c Simanek EE, McGarvey GJ, Jablonski JA, Wong C.-H. Chem. Rev. 1998; 98: 833
• 10d Wittmann V. In Highlights in Bioorganic Chemistry: Methods and Applications . Schmuck C, Wennemers H. Wiley-VCH; Weinheim: 2004: 203
• 10e Ernst B, Magnani JL. Nat. Rev. Drug Discovery 2009; 8: 661
• 10f Smith BA. H, Bertozzi CR. Nat. Rev. Drug Discovery 2021; 20: 217
• 11 Serhan CN, Ward PA, Gilroy DW. Fundamentals of Inflammation . Cambridge University Press; Cambridge: 2014
• 12a Dernedde J, Enders S, Reissig H.-U, Roskamp M, Schlecht S, Yekta S. Chem. Commun. 2009; 932
• 12b Roskamp M, Enders S, Pfrengle F, Yekta S, Dekaris V, Dernedde J, Reissig H.-U, Schlecht S. Org. Biomol. Chem. 2011; 9: 7448
• 13 Click reactions employing propargylic ethers 6 and 7 and benzylic biazides also provided more flexible bivalent carbohydrate mimetic precursors, see: Reissig H.-U, Yu F. Beilstein J. Org. Chem. 2023; 19: 1399
• 14a Huisgen R. Angew. Chem. Int. Ed. Engl. 1963; 2: 565 ; Angew. Chem. 1963, 75, 604
• 14b Tornøe CW, Christensen C, Meldal M. J. Org. Chem. 2002; 67: 3057
• 14c Rostovtsev VV, Green LG, Fokin VV, Sharpless KB. Angew. Chem. Int. Ed. 2002; 41: 2596 ; Angew. Chem. 2002, 114, 2708

For selected reviews, see:
• 15a Meldal M, Tornøe CW. Chem. Rev. 2008; 108: 2952
• 15b Arãgao-Leoneti V, Campo VL, Gomes AS, Field RA, Carvalho I. Tetrahedron 2010; 66: 9475
• 15c Haldon E, Nicasio MC, Perez PJ. Org. Biomol. Chem. 2015; 13: 9528
• 15d Kacprzak K, Skiera I, Piasecka M, Paryzek Z. Chem. Rev. 2016; 116: 5689
• 15e Breugst M, Reissig H.-U. Angew. Chem. Int. Ed. 2020; 59: 12293 ; Angew. Chem. 2020, 132, 12389
• 15f Pan R, Pathak T. ARKIVOC 2022; (vi): 81
• 16 Khdor O, Ouyang A, Skibo EB. J. Org. Chem. 2006; 71: 5855
• 17a Chiara JL, Destabel C, Gallego P, Marco-Contelles J. J. Org. Chem. 1996; 61: 359
• 17b Jung SH, Lee JE, Koh HY. Bull. Korean Chem. Soc. 1998; 19: 33
• 17c Keck GE, Wager TT, McHardy SF. Tetrahedron 1999; 55: 11755
• 17d Pulz R, Al-Harrasi A, Reissig H.-U. Org. Lett. 2002; 4: 2353
• 17e Revuelta J, Cicchi S, Brandi A. Tetrahedron Lett. 2004; 45: 8375
• 17f Bressel B, Reissig H.-U. Org. Lett. 2009; 11: 527
• 18a Helms M. Dissertation . Freie Universität Berlin; Germany: 2005
• 18b Moinizadeh N, Klemme R, Kansy M, Zimmer R, Reissig H.-U. Synthesis 2013; 45: 2752
• 19 Previously we found that the hydrogenolysis of 4 in the presence of palladium on charcoal can also stop at the stage of compound 13. However, this result strongly depended on the batch of the palladium catalyst employed and was not fully reproducible because of over-reduction. Nevertheless, these results indicate that the N–O bond is cleaved before the azido group is reduced. Al-Harrasi, A.; Reissig, H.-U., unpublished results.
• 20 Yekta S, Prisyazhnyuk V, Reissig H.-U. Synlett 2007; 2069
• 21 Suárez JR, Trastoy B, Pérez-Ojeda ME, Marín-Barios R, Chiara JL. Adv. Synth. Catal. 2010; 352: 2515
• 22a Cavender CJ, Shiner VJ. J. Org. Chem. 1972; 37: 3567
• 22b Zaloom J, Roberts DC. J. Org. Chem. 1981; 46: 5173
• 22c Alper PB, Hung S.-C, Wong C.-H. Tetrahedron Lett. 1996; 37: 6029
• 23 Chan TR, Hilgraf R, Sharpless KB, Fokin VV. Org. Lett. 2004; 6: 2853
• 24 Dhamale OP, Zhong C, Al-Mafraji K, Boons GJ. Org. Biomol. Chem. 2014; 12: 2087
• 25 Schweiger RG. Carbohydr. Res. 1972; 21: 219
• 26 Zhu S.-Z. J. Chem. Soc., Perkin Trans. 1 1994; 2077
• 27 These data were taken from: Al-Harrasi A. Dissertation . Freie Universität Berlin; Germany: 2005