An Improved, Versatile, and Easily Scalable Synthesis of Sphingomyelins: Application to Stable Isotope Labeling

Abstract

With a view to make conveniently labeled mass spectrometry standards available, a set of deuterated sphingomyelins were prepared by a new expedient, flexible, robust, scalable, and high-yielding synthetic scheme starting from 2-azido-3-O-benzoylsphingosine as the key intermediate. Unlike previously published procedures, this work emphasizes the benefit arising from the choice of the azido function as a masking group for the reactive primary amine during the troublesome, though crucial, phosphorylation step.

Key words

sphingomyelin - sphingosine - stable isotope - deuterium - mass spectrometry standard - chemical synthesis

• References

• 1 Rao RP, Vaidyanathan N, Rengasamy M, Oommen AM, Somaiya N, Jagannath MR. J. Lipids 2013; 178910
• 2 Arenz C. Future Med. Chem. 2017; 9: 1687
• 3 Wasserstein M, Dionisi-Vici C, Giugliani R, Hwu W.-L, Lidove O, Lukacs Z, Mengel E, Mistry PK, Schuchman EH, McGovern M. Mol. Genet. Metab. 2019; 126: 98
• 4 Nageswara RR. Mod. Appl. Pharm. Pharmacol. 2017; DOI:
• 5 Atzrodt J, Derdau V, Kerr WJ, Reid M. Angew. Chem. Int. Ed. 2018; 57: 1758
• 6 Atzrodt J, Derdau V, Kerr WJ, Reid M. Angew. Chem. Int. Ed. 2018; 57: 3022
• 7 Allen J, Brasseur DM, De Bruin B, Denoux M, Pérard S, Philippe N. J. Labelled Compd. Radiopharm. 2007; 50: 342
• 8 Byun H.-S, Bittman R. Chem. Phys. Lipids 2010; 163: 809
• 9 Bartels T, Lankalapalli RS, Bittman R, Beyer K, Brown MF. J. Am. Chem. Soc. 2008; 130: 14521
• 10 Matsumori N, Yasuda T, Okazaki H, Suzuki T, Yamaguchi T, Tsuchikawa H, Doi M, Oishi T, Murata M. Biochemistry 2012; 51: 8363
• 11a Yasuda T, Kinoshita M, Murata M, Matsumori N. Biophys. J. 2014; 106: 631
• 11b Yo Yano Y, Hanashima S, Yasuda T, Tsuchikawa H, Matsumori N, Kinoshita M, Al Sazzad MA, Slotte JP, Murata M. Biophys. J. 2018; 115: 1530
• 11c Erratum: Yo Yano Y, Hanashima S, Yasuda T, Tsuchikawa H, Matsumori N, Kinoshita M, Al Sazzad MA, Slotte JP, Murata M. Biophys J. 2019; 116: 1575
• 12 Mehnert T, Jacob K, Bittman R, Beyer K. Biophys. J. 2006; 90: 939
• 13 Cui J, Matsuoka S, Kinoshita M, Matsumori N, Sato F, Murata M, Ando J, Yamakoshi H, Dodo K, Sodeoka M. Bioorg. Med. Chem. 2015; 23: 2989
• 14 Parameswar AR, Hawkins JA, Mydock LK, Sands MS, Demchenko AV. Eur. J. Org. Chem. 2010; 3269
• 15a Sonnenberger S, Lange S, Langner A, Reinhard HH, Neubert RH. H, Dobner B. J. Labelled Compd. Radiopharm. 2016; 59: 531
• 15b Zimmermann P, Schmidt RR. Liebigs Ann. Chem. 1988; 663
• 16a Carmen D, Heckhoff S, Oswald B, Rebmann P, Peer A, Gonzalez M, Sauter P. Patent US 20140275590A1, 2014
• 16b Byun H.-S, Erukulla RK, Bittman R. J. Org. Chem. 1994; 59: 6495
• 16c Dong Z, Butcher JA. Jr. Chem. Phys. Lipids 1993; 66: 41
• 17 Yamamoto T, Hasegawa H, Hakogi T, Katsumura S. Org. Lett. 2006; 8: 5569
• 18 Sandbhor MS, Key JA, Strelkov IS, Cairo CW. J. Org. Chem. 2009; 74: 8669
• 19 Bruzik KS. Biochim. Biophys. Acta 1988; 939: 2: 315