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Meng Que

The absolute configuration of prunioside A from Spiraea prunifolia and biological activities of related compounds. Meng Que. Content. 1. Abstract 2. Introduction 3. Experimental 4. D iscussion. Phytochemistry , 2003 .

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Meng Que

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  1. The absolute configuration of prunioside A from Spiraeaprunifoliaand biological activities of related compounds MengQue

  2. Content • 1. Abstract • 2. Introduction • 3. Experimental • 4. Discussion

  3. Phytochemistry, 2003. • H Oh, G S Oh, W G S, et al. Prunioside A: A New Terpene Glycoside from Spiraeaprunifolia [J]. J. Nat. Prod. 2001, 64: 942-944.

  4. 1. Abstract • The configurations at C-5 and C-6 were determined. • The modified Mosher’s method, CD analysis, and 13C NMR spectroscopic data analysis of an acetonidederivative. • Other compounds related to pruniosideA have inhibitory effects on the synthesis of nitric oxide in LPS-stimulated macrophage-like RAW 264.7 cells.

  5. 2. Introduction • PruniosideA (1) has been isolated from the methanol extract of Spiraeaprunifoliavar. simpliciflora. • The roots of this plant have been used traditionally for the treatment of malaria, fever, and emetic conditions.

  6. 3. Experimental 3.1. Extraction and isolation of prunioside A (1) Collected from Iksan City, Chonbuk Province, Korea in May 2000. Fresh roots were dried in a well-ventilated darkroom. Symmetry Pre C18 column (1.9 × 30 cm; 7-μm particle size; flow rate of 4 ml/min)

  7. 3.2. Determination of the absolute configurations of Prunioside A (1) • The relative configurations of C-5 and C-6 could not be established from the NMR data, and exhaustive efforts to obtain crystals of 1 or 1a were unsuccessful.

  8. 3.2. Determination of the absolute configurations of Prunioside A (1) Enzymatic hydrolysis of 1 Mosher’s method Hydrolysis of 3 under mild alkaline condition It has been reported that acetonides of syn and anti-1,2-diols can be unambiguously distinguished by the 13C NMR chemical shifts of the acetonide methyl groups. (Dana and Danechpajouh, 1980; Solladie′ et al., 1997) Formation of acetonide9 Formation of 8

  9. Preparation of (S)-MTPA ester 5 and (R)-MTPA ester 6

  10. Mosher’s method

  11. Mosher’s method

  12. Mosher’s method • The DdSR values must be sufficiently large and be above the level of experimental error. • The distribution of the signs of the parameter DdSR must be uniform for a given substituent. • If the sign of DdSR is negative for one substituent , then the sign of DdSR for the other substituent must be positive.

  13. Determination of the configuration at C-6

  14. Hydrolysis of 3 under mild alkaline condition

  15. Enzymatic hydrolysis of prunioside A (1) with tannase

  16. Formation of acetonide9 • A smaller non-equivalence between the gem-dimethyl groups 3 for the syndiol, 0.8 ppm, than for the antidiol, 3 ppm. • The chemical shifts for the two acetonidemethyl groups (26.4 and 26.8) in the 13C NMR spectrum of 9 were typical of gem-dimethyl groups of erythro-diolacetonides(Dana and Danechpajouh, 1980; Solladie′ et al., 1997).

  17. Formation of 8

  18. Exciton chirality method

  19. 3.2. Determination of the absolute configurations of Prunioside A (1) • The CD spectrum of di-p-bromobenzoate(8) showed a clear positive excitonsplit [first Cotton effect at 256 nm (Δε=+4.48), and a second Cotton effect at 239 nm (Δε =-5.95)]. • Afford clear evidence for the 5S and 6R configurations.

  20. 3.3. Biological activities • Nitric oxide (NO) is produced by nitric oxide synthases in certain cells, and has been implicated in a wide range of physiological and pathological processes. • NO synthases can be classified into two major groups. • The inducible isoform of NO synthase (iNOS) plays important roles in macrophage-mediated cytotoxicity.

  21. 3.3. Biological activities Compounds 4 and 11 showed dose-dependent inhibition of NO production, with IC50 values of 2.2 and 5.1 mg/ml, respectively, while compound 10 showed a very weak inhibitory effect (12% inhibition at 10 mg/ml).

  22. RAW 264.7 cells LPS Different dose of 3 Mesurement of nitrite concentration Dose-dependent inhibition of NO production was observed with an IC50 value of 3.0 mg/ml.

  23. 4. Discussion • We can try to obtain crystals of 10 or 11. • CD spectrum could be used to determine the absolute configurations of PruniosideA. • The biological test has been a hotspot, but it’s very complicated and difficult to administrate.

  24. Thanks for your attention

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