A Modular Synthesis of Fluorinated, Chiral Polar Lipids

Abstract

The synthesis of a small collection of chiral, polar lipids is described starting from (S)-solketal and epichlorohydrin.

Key words

amphipathic - β-fluoroamines - coupling - fluorine - lipid - synthesis

References

• 1a Li S. Huang L. Gene Therapy  2000,  7:  31 
• 1b Cavazzana-Calvo M. Thrasher A. Mavilio F. Nature  2004,  427:  779 
• 1c Hoag H. Nature  2005,  435:  530 
• 2a Miller AD. Angew. Chem. Int. Ed.  1998,  37:  1768 
• 2b Elsabahy M. Wazen N. Bayo-Puxan N. Deleavey G. Servant M. Damha M. Leroux JC. Adv. Funct. Mater.  2009,  19:  3862 
• 2c Zhu L. Mahato RI. Expert Opin. Drug. Deliv.  2010,  7:  1209 
• 3a Sparr C. Schweizer WB. Senn HM. Gilmour R. Angew. Chem. Int. Ed.  2009,  48:  3065 
• 3b Bucher C. Sparr C. Schweizer WB. Gilmour R. Chem. Eur. J.  2009,  15:  7637 
• 3c Sparr C. Tanzer E.-M. Bachmann J. Gilmour R. Synthesis  2010,  1394 
• 3d Bucher C. Mondelli C. Baiker A. Gilmour R. J. Mol. Catal. A: Chem.  2010,  327:  87 
• 3e Sparr C. Gilmour R. Angew. Chem. Int. Ed.  2010,  49:  6520 
• 3f Bucher C. Gilmour R. Angew. Chem. Int. Ed.  2010,  49:  8724 
• 3g Paul S. Schweizer WB. Ebert M.-O. Gilmour R. Organometallics  2010,  29:  4424 
• 5 Smart BE. J. Fluorine Chem.  2001,  109:  3 
• 6 Hodges JA. Raines RT. J. Am. Chem. Soc.  2003,  125:  9262 
• For examples of related reactions see
• 7a Lemaire M. Jeminet G. Gourcy J.-G. Dauphin G. Tetrahedron: Asymmetry  1993,  4:  2101 
• 7b Cassel S. Debaig C. Benvegnu T. Chaimbault P. Lafosse M. Plusquellec D. Rollin P. Eur. J. Org. Chem.  2001,  875 
• 7c Kawagishi T. Yoshikawa K. Ubukata M. Hamada M. Nakajima N. Heterocycles  2006,  69:  107 

4

(+)-(S)-Solketal is available from a number of suppliers including TCI-Deutschland [25 g = 364.36 CHF]. Epichlorohydrin(racemic) was purchased from Sigma-Aldrich [100 g = 39.76 CHF].

8

Both cis-4-fluoroproline [1 g = 380.77 CHF] and trans-4-fluoroproline [1 g = 559.93 CHF] are commercially available from Bachem.