title: Novel synthetic method for the preparation of amphiphilic hyaluronan by means of aliphatic aromatic anhydrides.
abstract: The present work describes a novel and efficient method of synthesis of amphiphilic hyaluronan (HA) by esterification with alkyl fatty acids. These derivatives were synthesized under mild aqueous and well controlled conditions using mixed aliphatic aromatic anhydrides. These anhydrides characterized by the general formula RCOOCOC6H2Cl3 can be easily prepared by the reaction of the corresponding fatty acid (R) with 2,4,6-trichlorobenzoyl chloride (TCBC) in the presence of triethylamine. The aliphatic aromatic anhydrides RCOOCOC6H2Cl3 then react with the polysaccharide and enable the synthesis of aliphatic acid esters of HA in good yields. No hydrolytic degradation of hyaluronic acid could be observed. Parameters controlling the degree of esterification were systematically studied. Fatty acids with different chain lengths can be introduced applying this methodology. The degree of substitution was decreasing with increasing length of hydrophobic chain. The reaction products were fully characterized by Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR), SEC-MALLS and chromatographic analyses. Although the esterified HA products exhibited aggregation in solution as demonstrated by NMR, microscopy and rheology, they were still water-soluble.
authors.affiliation: Contipro Pharma a.s., Dolni Dobrouč 401, 561 02 Dolni Dobrouč, Czech Republic. Electronic address: huerta-angeles@contipro.com.
authors.forename: Gloria
authors.initials: G
authors.lastname: Huerta-Angeles
authors.affiliation: Contipro Pharma a.s., Dolni Dobrouč 401, 561 02 Dolni Dobrouč, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Bobek
authors.affiliation: Contipro Pharma a.s., Dolni Dobrouč 401, 561 02 Dolni Dobrouč, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Příkopová
authors.affiliation: Contipro Pharma a.s., Dolni Dobrouč 401, 561 02 Dolni Dobrouč, Czech Republic.
authors.forename: Daniela
authors.initials: D
authors.lastname: Šmejkalová
authors.affiliation: Contipro Pharma a.s., Dolni Dobrouč 401, 561 02 Dolni Dobrouč, Czech Republic.
authors.forename: Vladimír
authors.initials: V
authors.lastname: Velebný
mesh_terms: D000812:Anhydrides / Q000737:chemistry*; D004951:Esterification; D005227:Fatty Acids / Q000737:chemistry*; D006820:Hyaluronic Acid / Q000138:chemical synthesis* / Q000737:chemistry; D006841:Hydrocarbons, Aromatic / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013501:Surface-Active Agents / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000812:Anhydrides; D005227:Fatty Acids; D006841:Hydrocarbons, Aromatic; D013501:Surface-Active Agents; D006820:Hyaluronic Acid
keywords: Fatty acids; Hyaluronic acid; Mixed aliphatic aromatic anhydrides; Symmetric anhydrides