| dc.description.abstract | Syntheses of and with Braun’s chiral auxiliary (R)-(+)-2-acetoxy-1,2,2-triphenylethanol were explored, for the syntheses long-chain 3(R)-hydroxy-oxylipins. The chiral auxiliary was used to stereoselectively synthesize 3-hydroxy-methyl-icosanoate. This was achieved through a
novel magnesium-mediated aldol compound of the auxiliary and the aldehyde octadecaenal. This intermediary compound was transesterified to 3-hydroxy-methyl-icosanoate. The stereoselective synthesis of 3-hydroxy-methyl-icosanoate shows acceptable enantiomeric excess by mosher ester analysis. However, absolute conformation was not confirmed. A novel reformatsky reaction protocol for the achiral synthesis of 3-hydroxy-methyl-icosanoate from octadecaenal was also developed. Hydrolysis of 3-hydroxy-methyl-icosanoate to 3-hydroxy-icosanoic acid was not completed due to time constraints.
Both the Swern oxidation and the Dess-Marin oxidation protocols were used for the synthesis of octadecaenal.
The polyunsaturated target compounds (all Z)-3(R)-hydroxyicosa-5,8,11,14-tetraenoic acid (3-HETE) and (all Z)-3(R)-hydroxyicosa-5,8,11,14,17-pentaenoic acid (3-HEPE) were not synthesized. (all Z)-docosa-4,7,10,13,16,19-hexaenoic acid (DHA) was iodolactionised via
the Corey lactonization protocol, then hydrolysed to the γ-diol acid (all Z)-4,5-dihydroxydocosa-7,10,13,16,19-pentaenoic acid. Oxidative cleavage to (all Z)-octadeca-3,6,9,12,15-pentaenal with sodium periodate or periodic acid did not yield a clean product
after purification.
The Braun chiral auxiliary is demonstrated to be a good acetate donor for stereoselective aldol reactions. Alternative synthetic protocols and further studies are required to maximise the potential of this auxiliary. | |
