A practical synthesis of long-chain iso-fatty acids (iso-C₁₂–C₁₉) and related natural products

Abstract

SummaryA gram-scale synthesis of terminally-branched iso-fatty acids (iso-C12–C19) was developed commencing with methyl undec-10-enoate (methyl undecylenate) (for iso-C12–C14) or the C15 and C16 lactones pentadecanolide (for iso-C15–C17) and hexadecanolide (for iso-C18–C19). Central to the approaches outlined is the two-step construction of the terminal isopropyl group through addition of methylmagnesium bromide to the ester/lactones and selective reduction of the resulting tertiary alcohols. Thus, the C12, C17 and C18 iso-fatty acids were obtained in three steps from commercially-available starting materials, and the remaining C13–C16 and C19 iso-fatty acids were prepared by homologation or recursive dehomologations of these fatty acids or through intercepting appropriate intermediates. Highlighting the synthetic potential of the iso-fatty acids and various intermediates prepared herein, we describe the synthesis of the natural products (S)-2,15-dimethylpalmitic acid, (S)-2-hydroxy-15-methylpalmitic acid, and 2-oxo-14-methylpentadecane.

Convenient and Environmentally Friendly Production of Isostearic Acid with Protonic Forms of Ammonium Cationic Zeolites

“…More recently, large‐pore zeolites such as faujasite and Beta structure (pore size >6 Å) and mesoporous zeolites (>15 Å) have been used for skeletal isomerization of ulc‐FA with better yield of bc‐FA. Some other synthetic methodologies have also been reported to introduce alkyl branches in fatty acid chains such as thermally initiated addition of alkanes to unsaturated fatty acids, three step synthesis of iso‐fatty acid through the addition of methylmagnesium bromide, Lewis acid induced hydroalkylation or co‐oligomerization of fatty acids . However in these procedures, high catalyst loadings, expensive synthetic methods, inadequate regeneration of used catalyst, low conversion of starting fatty acids, and suppression of dimer acid formation are issues that still need to be addressed.…”

Synthesis, Optical Rotation, and Absolute Configurations of Santinols

“…The filtrate was concentrated on a rotary evaporator to give acid 13 as a white solid (270 mg, 1.18 mmol, 92 % from 12 ), m.p. 49–50 °C (ref 15. m.p.…”

Alkyl‐Branched Fatty Compounds: Hydro‐Alkylation of Non‐Activated Alkenes With Haloalkanes Mediated by Ethylaluminum Sesquichloride

“…The alkylation of unsaturated fatty compounds containing an internal double bond such as oleic acid is of great interest since the resulting branched fatty compounds are known for their improved application properties in the area of lubricants and cosmetics including, for example, good spreadability, low viscosity and good oxidative and hydrolytic stability . Most interestingly, hydro‐isopropylation and hydro‐ sec ‐butylation of ω‐unsaturated fatty acids opens an easy synthetic access to the important classes of iso ‐ and anteiso ‐fatty acids . The synthesis of unsaturated alkyl branched oleochemicals is possible by addition of, for example, propen to ethyl linoleate in the presence of a bimetallic catalyst system consisting of RhCl 3 and Pd(MeCN) 2 Cl 2 .…”

“…[22][23][24][25] Most interestingly, hydro-isopropylation and hydro-sec-butylation of v-unsaturated fatty acids opens an easy synthetic access to the important classes of isoand anteiso-fatty acids. [2,26] The synthesis of unsaturated alkyl branched oleochemicals is possible by addition of, for example, propen to ethyl linoleate in the presence of a bimetallic catalyst system consisting of RhCl 3 and Pd(MeCN) 2 Cl 2 . [27] Furthermore, saturated alkyl branched fatty compounds can be obtained by the zeolite-catalyzed isomerization of oleic acid followed by hydrogenation.…”