Synthesis of fatty acid conjugates with phenols, carbohydrates, amines, and CH‐acidic compounds by Pd(0)‐catalyzed allylic substitution

Abstract

The efficiency of a pharmaceutical can be increased by connecting it to a fatty acid. Nucleophilic allylic substitution of methyl 10‐undecenoate and methyl oleate with palladium(0) as catalyst is explored to see, whether this reaction is useful for such connections with regard to yield and selectivity. For that purpose the allylic CH‐bonds in methyl 10‐undecenoate and methyl oleate were oxidized with selenium dioxide and tert‐butylhydroperoxide. The obtained allylic alcohols were then activated by conversion into their methyl carbonates. Allylic substitution was performed with O‐nucleophiles as methanol, carbohydrates, and different phenols as α‐tocopherol and estradiol; furthermore N‐ and C‐nucleophiles were applied. The yields of substitution products were in the range of 37–98%. High yields of conjugates were obtained with phenols, even when the hydroxy group was sterically shielded. These conjugates have an ether bond, a CN or a CC bond as link. They should have the advantage to be more stable in body fluids than the frequently applied conjugates being connected by the less inert ester bond. Triesters and dicyanoesters obtained with C‐nucleophiles can be possibly used as cross linkers for polyesters and polyamides. Practical applications: These conjugates should be more stable in cells and body fluids than the frequently applied conjugates being connected by the less inert ester bond. Triesters and dicyanoesters obtained with C‐nucleophiles can be possibly used as cross linkers for polyesters and polyamides. Methyl 9‐hydroxy‐10‐undecenoate is prepared by allylic oxidation from methyl 10‐undecenoate. After esterification to the methyl carbonate this leaving group is substituted via Pd(0)‐catalysis by O‐, N‐, and C‐nucleophiles to afford fatty acid conjugates. Similarly methyl oleate is converted.

Synthetic Transformations for the Valorization of Fatty Acid Derivatives

“…The synthesis of allylic alcohols from methyl oleate was described in 2016 by irradiation in the presence of a photosensitizer tetraphenylporphine (TTP) and oxygen. 122 By adding triphenylphosphine, the formed allylic hydroperoxide was reduced to the allylic alcohol, which was isolated as a mixture of two regiomers in 92% yield (Scheme 13). The ratio of isomers is assumed to be ca.…”

Thymol-Modified Oleic and Linoleic Acids Encapsulated in Polymeric Nanoparticles: Enhanced Bioactivity, Stability, and Biomedical Potential

“…Recent studies addressed the stability improvement in body fluids [ 8 ], the cell penetration enhancement [ 9 ], and the capacity for synergetic improvement of biological properties of FAs conjugated with phenolic compounds [ 10 , 11 ].…”