ably 5,8-, 4,7- and 4,s-dithioloctanoic acids, respectively. After spontaneous air oxidation in dilute solution, the preparations were assayed for biological activity in the pyruvate oxidation factor assay.j In one experiment, a 1-g. sample of each ether-acid was treated with one gram of thiourea and one milliliter of 40 per cent. hydrobromic acid in a sealed tube a t 120’ for ninety minutes, followed by hydrolysis with twenty-five milliliters of concentrated ammonium hydroxide a t 120’ for forty-five minutes in the presence of a trace of ferrous sulfate. The yields of pyruvate oxidation factor activity, “lipoic acid,” were as follows I
Fig. 1.--Infrared absorptiori spectra ( S u j o l mulls), Perkin Elmer spectrophotometer, model 12C : Curve -4, authentic 17-hydroxycorticosterone; Curve B, crystalline product from Streptomyces J‘rtadinc. coriversion of 1l-desoxy-li-hydroxycorticosterone.
4-(a-Tetrahydrofury1)-butyric acid 20,000 unit> &a-(a’-hlethyltetrahydrofuryl)-propionic acid 500 units 3-(a-Tetrahytiropyrany1)-propionic acid 2.50
Under similar conditions with a twelve-hour heating period, 0.5 g. of 4-( a-tetrahydrofury1)butyric acid gave 1,200,000 units of activity. These observations favor one of the optical isomers the Streptomyces fvadiae conversion as 1T-hydroxy- of the cyclic disulfide derived from 5,s-dithiolcorticosterone. octanoic acid as the structure of cy-lipoic acid. The authors wish to acknowledge the helpful The active material, obtained from 4-(a-tetrainterest shown in this work by Dr. J. S. Evans.lo hydrofury1)-butyric acid, in these and similar preparations, showed a behavior in the bioauto(IO) Attention is directed to t h e microbiological oxidation of steroids a t carbon 11, using fungi of t h e order Mucorales, a s reported graphic6 and counter-current’ procedures characby Peterson a n d M u r r a y , THISJOURXAL, 74, 1871 (1962). teristic of a-lipoic acid ;, including the formation KESE.4RCIi LABORATORIES DOXALD R. COLISGSWORTH of a more polar material2 referred to as “/I-lipoic TKEUPJOHNCOMPANY MARIP. BRUNNER acid.” In the pyruvate oxidation factor assay, an ~unsslusand G 11. 1.. Schnakciipharmacological activity resembling that of the l ~ w g‘l‘ii~s J O U X N . \ L , 73, 5920 (1951J. \-eratrum alkaloids.2 I n view of the recent interest ( 3 , I . J. Iui&diis, i h i d . , 74, 27%1 ~IU.50). I
