Unsaturated Fatty Acids. II. Synthesis of cis- and trans-5-Octenoic Acids

Abstract

A program was recently initiated in these laboratories with the intention of elucidating some of the features of the metabolism of straight-chain fatty acids having carbon-carbon unsaturation. In connection with these studies (2) it became necessary to have several octenoic acids of high purity and established structure.The present publication reports the synthesis and characterization of two new members of the series of eleven theoretically possible octenoic acids, only four of which have been described previously (3).By suitable combination and application of the chloroalkyne synthesis of Henne and Greenlee (4) and stereospecific catalytic semihydrogenation (5), Strong and his associates ( 6) have recently provided a straight-forward general method for the preparation of straight-chain cfs-mono-enoic fatty acids. As shown in the following diagram, this procedure has now been applied successfully to the synthesis of m-5-octenoic acid (III):Trimethylene iodochloride was condensed with sodium butynide in a liquid ammonia medium to give 1 -chIoroheptyne-4 (I). The chloro group of this intermediate was then replaced by cyano, using sodium cyanide, and the resulting nitrile (which was not isolated) hydrolyzed directly to II, m.p. 80.3 The overall yield of II from trimethylene iodochloride was 30%. That II has the expected structure was showm by catalytic hydrogenation, in which process two 1 Paper I of this series, entitled "A Total Synthesis of Linoleic Acid," was published recently elsewhere (1).3 This paper is based on work performed under Contract AT-04-1-GEN-12 between the Atomic Energy Commission and the University of California at Los Angeles. 3 The preparation of 5-octynoic acid (II) by a procedure essentially the same as that employed in these laboratories was reported by Newman and Wotiz (7) while the present work was in progress. Completion of the synthesis of all the octynoic acids by Newman and Wotiz, together with the stereospecific semireduction methods revealed here and elsewhere (6) makes the full series of octenoic acids potentially available.

Identification of possible intermediates in the mitochondrial fatty acid chain elongation system

“…The former was obtained by a Doebner-type procedure using 10% pyridine in acetic acid (Jenny and Grob, 1953). If collidine was used to solubilize the reactants, then 3 acids were produced in good yields (Howton and Davis, 1951). The 3-keto fatty acid esters were obtained by the acetoacetate condensation method of Stallberg-Stenhagen and Stenhagen (1944), except that the acyl chloride was reacted with the sodioethyl acetoacetate in benzene rather than ether.…”

Twofold Alkylations of Sodium Diphenylmethide with Methylene Halides to Form Bisbenzhydrylmethylene Hydrocarbons. Alkylations of Sodium Triphenylmethide1

“…The cooled solution was extracted with three portions of ether, and the extracts were washed with water and sodium carbonate solution. Material recovered from the ether after carbonate extraction amounted to 50 mg. and showed infrared absorption at 5,66 µ, 5.77 µ, and 5.86 µ. Acid recovered from the sodium carbonate extract showed an infrared spectrum identical with that of the starting material.…”

The Chemistry of the Alkali Amides.

“…1. Alkylation reactions Sodium and lithium acetylide and some of their substituted derivatives, prepared by the reaction of acetylene or the monosubstituted acetylenes with sodium amide or lithium amide in liquid ammonia, have been alkylated with the following classes of reagents: alkyl halides (132, 133, 177, 281, 406-8, 573, 587, 651, 682, 858), dihaloalkanes (8,9,439,538,657,658,717,842), haloepoxides (396,399), dialkyl sulfates (218, 406, 549, 550, 858, 867), and acetals (520). Since the alkylation of the metallic derivatives of acetylene was thoroughly reviewed in 1949 by Jacobs (456), only a few examples of the most recent work will be discussed.…”