ORGANIC SYNTHESIS LABORATORY

The main function of this laboratory is to provide investigators with chemical compounds that are not commercially available. Some of the custom syntheses performed by the facility staff are new, while others have been reported in the literature. Facility staff members also provide many additional services to Fox Chase scientists, including: provision of analytical services such as nuclear magnetic resonance spectroscopy (NMR), thin-layer chromatography (TLC), and Fourier transform infrared spectroscopy (FT-IR); custom purification of purchased chemicals; maintenance of a large variety of chemical reagents for use by the research staff; and consultation with staff on proper usage and disposal of research chemicals. The facility staff operates a preparative high performance liquid chromatography (HPLC) system. This instrument is used to purify reaction intermediates and synthesized products. A few representative syntheses carried out in the last year are described below.

OLTIPRAZ METABOLITE      (Prepared for Clapper)

Both of these novel compounds are being tested in vivo for their ability to induce phase II detoxication enzyme activity. While the chemopreventive activity of oltipraz has been established, the search continues for more potent inducers which do not require metabolic activation. The oltipraz analog (X=S) was synthesized by reduction of the disulfide bond with sodium borohydride in ethanol. The oxygen analog was synthesized by reduction of the disulfide bond with sodium hydrogen telluride in ethanol. Both compounds were purified by column chromatography over silica and analyzed by TLC, IR, MS and NMR.

1,4-DIBUTOXY-6H-INDOLO[2,3-B]QUINOXALINE     (Prepared for C. Smith)

The quinoxaline compound is being studied as a p-glycoprotein antagonist. This interesting compound was synthesized from 2,3-diamino-1,4-dibutoxybenzene and isatin. The 2,3-diamino-1,4-dibutoxybenzene was synthesized in three steps using the method of A.V. Ivashchenko and I.F. Agafonova (Khim. Geterotsikl. Soedin. 2:249, 1981). The product was analyzed by ¹H and ¹³C NMR.

2-FLUORO AND 2,2-DIFLUOROSUCCINIC ANHYDRIDE     (Prepared for Jaffe)

These compounds are potential precursors for the enzymatic synthesis of fluorinated analogs of 5-aminolevulinic acids. Fluorinated 5-aminolevulinic acid analogs may be powerful probes of the porphobilinogen synthase catalyzed reactions. 2-Fluorosuccinic acid was prepared from 2-hydroxysuccinic acid using a three step procedure described by J.B. Campbell and J.S. Johnston (J. Labelled Compd. Radiopharm. 27:1353, 1989). The acid was converted to its anhydride using trifluoroacetic acid similar to the method of F.J. Leeper and M. Rock (J. Fluroine Chem. 51:381, 1991). Difluorosuccinic anhydride was synthesized from difluorosuccinic acid and acetic anhydride under an inert atmosphere. This novel compound was analyzed by ¹H and ¹³C NMR.

Illustrations or unpublished data in these reports should not be used without permission of the author.

Fox Chase Cancer Center

Scientific Report 1998