Alberto A. Leon

High Performance Liquid Chromatographic Determination of Nordihydroguaiaretic Acid

Abstract A high performance liquid chromatography (HPLC) method was developed for the detection and quantitation of nordihydroguaiaretic acid (NDGA). Very low concentrations of NDGA in various extracts are detectable, thus making the method more sensitive than other previously reported analytical techniques. NDGA was extracted from leaves of Larrea divaricata as well as from rodent food containing NDGA. Since rats are fed NDGA in studies that examine the development of renal cystic disease, we modified extraction procedures to permit isolation of NDGA from tissue and serum samples.

Chemical reactivities and mutagenicities of a series of chloromethylbenzo[a]pyrenes

The chemical and mutagenic properties of a series of chloromethylbenzo[a]pyrenes (chloromethyl-BaP) (chloromethyl groups in position 1-, 4-, 5-, 6-, 10-, 11- or 12-) were studied in order to address the question of the importance of arylmethyl carbocations as possible ultimate carcinogens of methylated polycyclic aromatic hydrocarbons (PAH). The rates of solvolysis of the series of chloromethyl-BaP in 50% aqueous acetone decrease in the order: 6 greater than 1 much greater than 4 greater than 12 greater than 5 greater than 10 greater than 11. There is a rough correlation (r = -0.80, P less than 0.05) between rates of solvolysis and the carbon chemical shifts of the methylene carbons. There is a good correlation (r = 0.98, P less than 0.001) between the rates of solvolysis and the gas phase stabilities of the carbocations, (M+ -35), obtained from mass spectral analysis. The mutagenicities of the series of chloromethyl-BaP in the Ames assay with strains TA98 and TA100 showed strong to very strong mutagenicities for the 4-, 5-, 10-, 11- and 12-isomers and weak mutagenicities for the 1- and 6-isomers. The corresponding hydroxymethyl-BaP were not mutagenic. The mutagenicities of some of the chloromethyl-BaP are among the highest reported for direct-acting (not requiring microsomal activation) mutagens in the Ames assay.

Synthesis of 1-chloroestradiol

The synthesis of the previously unknown 1-chloroestradiol (1), is reported. Addition of N-chlorosuccinimide/NaI in dioxane to 4-amino-estradiol 3-methyl ether (2), resulted in exclusive chlorination of the 1-position. Subsequent deamination and demethylation afforded 1 in good yields.

Preparation of B-ring brominated derivatives of estradiol

The preparation of 6 beta-methoxy-7 alpha-bromoestradiol (1) is reported. Addition of in situ-generated BrOMe to 6-dehydroestradiol 3-tetrahydropyranyl ether (4a) afforded the expected addition product. Removal of the tetrahydropyranyl protective group was carried out by mild acid hydrolysis to afford 1 in good yields. This base-sensitive compound is chemically stable over long periods of time.