Tetra-glucopyranosyl Diterpene ent-Kaur-16-en-19-oic Acid and ent-13(S)-Hydroxyatisenoic Acid Derivatives from a Commercial Extract of Stevia rebaudiana (Bertoni) Bertoni.

Stevia rebaudiana and its diterpene glycosides are one of the main focuses of food companies interested in developing novel zero calorie sugar substitutes since the recognition of steviol glycosides as Generally Recognized as Safe (GRAS) by the United States Food and Drug Administration. Rebaudioside A, one of the major steviol glycosides of the leaves is more than 200 times sweeter than sucrose. However, its lingering aftertaste makes it less attractive as a table-top sweetener, despite its human health benefits. Herein, we report the purification of two novel tetra-glucopyranosyl diterpene glycosides 1 and 3 (rebaudioside A isomers) from a commercial Stevia rebaudiana leaf extract compounds, their saponification products compounds 2 and 4, together with three known compounds isolated in gram quantities. Compound 1 was determined to be 13-[(2-O-ß-d-glucopyranosyl-6-O-ß-d-glucopyranosyl-ß-d-glucopyranosyl) oxy]ent-kaur-16-en-19-oic acid-ß-d-glucopyranosy ester (rebaudioside Z), whereas compound 3 was found to be 13-[(2-O-ß-d-glucopyranosyl-3-O-ß-d-glucopyranosyl-ß-d-glucopyranosyl) oxy]ent-hydroxyatis-16-en-19-oic acid -ß-d-glucopyranosy ester. Two new tetracyclic derivatives with no sugar at position C-19 were prepared from rebaudiosides 1 and 3 under mild alkaline hydrolysis to afford compounds 2 13-[(2-O-ß-d-glucopyranosyl-6-O-ß-d-glucopyranosyl-ß-d-glucopyranosyl) oxy]ent-kaur-16-en-19-oic acid (rebaudioside Z1) and 4 13-[(2-O-ß-d-glucopyranosyl-3-O-ß-d-glucopyranosyl-ß-d-glucopyranosyl) oxy]ent-hydroxyatis-16-en-19-oic acid. Three known compounds were purified in gram quantities and identified as rebaudiosides A (5), H (6) and J (7). Chemical structures were unambiguously elucidated using different approaches, namely HRESIMS, HRESI-MS/MS, and 1D-and 2D-NMR spectroscopic data. Additionally, a high-quality crystal of iso-stevioside was grown in methanol and its structure confirmed by X-ray diffraction.

Bioactive (+)-manzamine A and (+)-8-hydroxymanzamine A tertiary bases and salts from Acanthostrongylophora ingens and their preparations.

The genus Acanthostrongylophora is famous for producing a wide array of manzamine alkaloids as natural hydrochloride salts. An examination of A. ingens has now yielded two tertiary bases, (+)-8-hydroxymanzamine A (1) and (+)-manzamine A (2), by chromatography over alumina using CHCl3-MeOH-NH3.H2O as solvent. In addition, (+)-8-hydroxymanzamine A hydrochloride (3) and (+)-manzamine A hydrochloride (4) were isolated under the same conditions from the same source by silica gel chromatography. The structures of 1-4 were determined from 1D- and 2D-NMR spectra and by circular dichroism experiments, and the spectral features of the bases 1 and 2 were found to be different from those of the salts 3 and 4. Compounds 3 and 4 were deprotonated by both A12O3 and strong base to afford 1 and 2, which were converted again to their respective salts 3 and 4. Both the compounds 1 and 3 showed equally potent in vitro antimalarial activity against chloroquine-sensitive (D6) and -resistant (W2) strains of P. falciparum (IC50 = 19.5 and 22.0 ng/mL vs. 27.0 and 36.5 ng/mL, respectively), while 2 was >3-fold less potent than 4 (IC50 = 20.8 and 25.8 ng/mL vs. 6.1 and 7.3 ng/mL, respectively). Compounds 1, 3 and 4 showed good antimicrobial activities against methicillin-resistant Staphylococcus aureus and Mycobacterium intracellulare and antileishmanial activity against Leishmania donovani promastigotes. In contrast, manzamine A base (2) showed relatively weaker antimicrobial, antileishmanial and cytotoxic activities [towards cancer (HepG2: Human hepatocellular carcinoma or hepatoma), and non-cancer cells (VERO: Monkey kidney fibroblast; LLC-PK11: Pig kidney epithelial)], compared with salt 4.

Clinic at the health food store? Employee recommendations and product analysis.

STUDY OBJECTIVES: To determine what products health food store employees recommend for depression, to analyze the content of these products based on label claims, and to evaluate employee statements or recommendations for accuracy and safety. METHODS: Twelve health food stores were selected for the study. One investigator approached an employee in each store and asked what they recommended for depression plus five additional questions regarding product use. Thirteen products containing St. John's wort were purchased and analyzed for hypericin and pseudohypericin content using high-performance liquid chromatography (HPLC). Total hypericin content was calculated by adding the values for hypericin and pseudohypericin. RESULTS: All 12 health food store employees recommended a St. John's wort supplement for treatment of depression. Furthermore, numerous comments made by employees regarding St. John's wort and the treatment of depression were unsafe and inaccurate. The HPLC analysis revealed that no product contained +/- 10% of the stated label claim for hypericin content, and two products contained 0% hypericin. The total hypericin content (hypericin plus pseudohypericin) of only two products was within +/- 10% of the label claim for hypericin. CONCLUSIONS: Health food store employees offer health care advice regarding treatment of depression with dietary supplements without proper scientific and medical training. Their comments could cause significant harm to customers. In addition, the inconsistencies of dietary supplement content continue to raise concern for individuals who use these agents as medical treatment.

Assessment of the quality of reference books on botanical dietary supplements.

OBJECTIVE: To review books on botanical dietary supplements (BDS) targeted to pharmacists and physicians to assess their overall quality as primary and secondary reference books. DESIGN: We purchased 52 books for initial review based primarily on their titles. After eliminating books not written for health care professionals and books that contained very limited information on BDS, we selected 22 texts to review in depth. PARTICIPANTS: The review team consisted of four pharmacists--two with PhDs in pharmacognosy, one with a PhD in pharmaceutics, and one with a PharmD who is a senior medical student. RESULTS: The authors, reviewers, and editors of some books were highly qualified; others lacked the qualifications to summarize scientific information in a balanced, unbiased manner. Many books contain unsubstantiated statements. The books judged to be of the highest quality provide primary references to support all statements and advise the reader that insufficient information is available to assess potential drug interactions and safety during pregnancy and lactation. CONCLUSION: The quality of the information presented in the reviewed books varies dramatically. The most critical information gaps include the potential for drug interactions and the safe use of specific botanicals during pregnancy and lactation.

Substituted indoloquinolines as new antifungal agents.

Cryptolepine (2) possesses desirable properties to serve as a lead in developing new antifungal agents. Using SAR techniques, several analogues of cryptolepine were designed to increase potency and to broaden the antifungal spectrum over several opportunistic microorganisms. A number of 2-substituted indoloquinolines have been synthesized and evaluated in antifungal screens and several have been shown to increase potency and expand the antifungal spectrum of cryptolepine. Comparison of MICs of a number of these analogues with standard antifungal agents, shows them to be comparable to Amphotericin B and Ketoconazole.