Mark D. Hylarides

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.

B-ring aromatization of estrogen derivatives

A novel method of B-ring aromatization of steroid derivatives is reported. Addition of BrCl in methanol to a non-aromatic B-ring double bond results in a rapid double elimination generating the aromatic B-ring. This procedure represents an effective method for conversion of an equilin to an equilenin nucleus.

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.