Some new reactions and some new syntheses of long-chain unsaturated acids

Abstract

Part I. The preparation and reactions of long-chain acids containing sulphur. Much is known about long-chain hydroxy esters and the epoxides which can be derived from them but information about the corresponding sulphur compounds is sparse. Using various methods, methyl 12-mercaptostearate, methyl 9-mercaptostearate, methyl 12-mercapto-oleate, methyl 12-mercapto-elaidate, methyl 9(10)-mercaptostearate, methyl 12"hydroxy-9(10)-mercaptostearate, methyl 9-hydroxy-12(13)-mercaptostearate and 1-mercapto-octadec-4- and 5-ene have been prepared. In reaction with sodium hydrogen sulphide without the rigorous exclusion of air the major product produced from methyl 9-mesyloxy- octadec-cis-12-enoate was methyl 9,12-epithiostearate. A similar result was observed with another 𝛾-mercapto alkene (1-mercapto-octadec-4-ene) and with a 8-mercapto alkene (l-mercapto-octadec-5-ene), but not with a hydroxy alkene (methyl ricinoleate). For confirmation of these conclusions methyl 9,12-epithiostearate was synthesised by an independent and unambiguous route. By an extension of the procedures applied for monomercapto esters, 1,2-dithiols (methyl erythro- and threo-9,10-dlmercapto- stearate), a 1,3-dithiol (methyl 10,12-dimercaptostearate), and a 1,4-dithiol (methyl 9,12-dimercaptostearate) have been prepared from the corresponding dihydroxy compounds. The 1,3- and 1,4-dithiols are readily converted to cyclic epidisulphides by oxidation. The infrared, NMR and mass spectral properties of these compounds have been investigated. 1,2-Epithiostearates (methyl cis and trans-9,10-epistearate) have been prepared by two different routes and their chromatographic (TLC, GLC) and spectroscopic (NMR, MS) behaviour studied. Part II: The synthesis of some C₁₆ and C ₁₈-acids of geneal formula CH₃ (CH₂)[sub]m(CH=CH)[sub]n CO₂H. Commercially available trienoic (△ 2, 4, 6) and tetraenoic acids (△2, 4, 6, 8) of medium chain length have been used successfully in the study of acyl-CoA synthetases of medium chain length specificity. But their activity with long chain acyl-CoA synthetases is rather low. The synthesis of C ₁₆ and C ₁₈ trienoic and tetraenoic acids has therefore been examined. The triene esters were successfully prepared by the reaction of appropriate aldehydes with phosphonates prepared from methyl 6-bromo-hexa-2,4-dienoate and the tetraene esters by interaction of 2,4-dienals with a phosphorane. The C₁₂, C₁₄ and C₁₆ dienals were prepared from l-methoxybut-1-en-3-yne by condensation with the appropriate saturated aldehyde. The chromatographic (GLC) and spectroscopic (UV, IR, NMR, and MS) properties of these acids have been examined and some simple thiol esters made. Their biochemical use as reagents for the estimation of long-chain Co-A synthetases is being conducted elsewhere.