Synthesis of Enantiomerically Pure α-Hydroxylated Nervonic Acid – A Chiral Pool Approach to α-Hydroxylated Unsaturated Fatty Acids

Abstract

A scalable and robust synthesis to α-hydroxylated nervonic acid is presented. The chiral-pool approach starts with malic acid and employs only highly reliable reactions such as Wittig reactions, protecting group conversions, and reductions. Depending on the configuration of malic acid being used as starting material both enantiomers can be obtained.

Key words

lipids - fatty acids - malic acid - nervonic acid

• References

• 1 Simons K, Ikonen E. Nature (London) 1997; 387: 569
• 2 Cinek T, Horejsi V. J. Immunol. 1992; 149: 2262
• 3 Hakomori S, Igarashi Y. J. Biochem. 1995; 118: 1091
• 4 Krauss K, Altevogt P. J. Biol. Chem. 1999; 274: 36921
• 5 Hakomori S. Proc. Natl. Acad. Sci. U.S.A. 2002; 99: 225
• 6 Ladisch S, Sweeley CC, Becker H, Gage D. J. Biol. Chem. 1989; 264: 12097
• 7 Kolter T, Sandhoff K. Angew. Chem. Int. Ed. 1999; 38: 1532
• 8 Windschiegl B, Steinem C. Langmuir 2006; 22: 7454
• 9 Iwayama Y, Ando H, Ishida H, Kiso M. Chem. Eur. J. 2009; 15: 4637
• 10 Konen DA, Silbert LS, Pfeffer PE. J. Org. Chem. 1975; 40: 3253
• 11 Andelic I, Myhren F, Skattebøl L, Öberg B, Datema R, Chattopadhyaya J. Acta Chem. Scand. 1985; 39: 231
• 12 Patterson JE, Ollmann IR, Cravatt BF, Boger DL, Wong C.-H, Lerner RA. J. Am. Chem. Soc. 1996; 118: 5938
• 13 A Bn-protected nervonic acid was obtained from glyceraldehyde; however, to remove the Bn group Birch conditions were necessary to retain the double bond: Cateni F, Zacchigna M, Zillic J, Luca GD. Helv. Chim. Acta 2007; 90: 282
• 14 Dutton F, Lee BH, Johnson SS, Coscarelli EM, Lee PH. J. Med. Chem. 2003; 46: 2057
• 15 Muller T, Coowar D, Hanbali M, Heuschling P, Luu B. Tetrahedron 2006; 62: 12025
• 16 Carpino LA. J. Am. Chem. Soc. 1993; 115: 4397