Article

The cephalostatins. 21. Synthesis of bis-steroidal pyrazine rhamnosides (1).

Department of Chemistry and Biochemistry, Arizona State University, PO Box 871604, Tempe, Arizona 85287-1604, United States.
Journal of Natural Products (impact factor: 3.13). 09/2011; 74(9):1922-30. DOI:10.1021/np200411p pp.1922-30
Source: PubMed

ABSTRACT The synthesis of bis-steroidal pyrazines derived from 3-oxo-11,21-dihydroxypregna-4,17(20)-diene (4) and glycosylation of a D-ring side chain with α-L-rhamnose have been summarized. Rearrangement of steroidal pyrazine 10 to 14 was found to occur with boron triflouride etherate. Glycosylation of pyrazine 10 using 2,3,4-tri-O-acetyl-α-L-rhamnose iodide led to 1,2-orthoester-α-L-rhamnose pyrazine 17b. By use of a persilylated α-L-rhamnose iodide as donor, formation of the orthoester was avoided. Bis-steroidal pyrazine 10 and rhamnosides 17b and 21c were found to significantly inhibit cancer cell growth in a murine and human cancer cell line panel. Pyrazine 9 inhibited growth of the nosocomial pathogen Enterococcus faecalis.

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  • Article: The rhamnose moiety of solamargine plays a crucial role in triggering cell death by apoptosis.
    L C Chang, T R Tsai, J J Wang, C N Lin, K W Kuo
    [show abstract] [hide abstract]
    ABSTRACT: Solamargine, solasodine and khasianine steroidal alkaloids are utilized to determine the role of carbohydrate moiety in the mechanism of apoptosis. The C3 side chain of solamargine, khasianine and solasodine contains 4'Rha-Glc-Rha2', 4'Rha-Glc and H, respectively. Solamargine possessed potent cytotoxicity to human hepatoma cells, while the cytotoxicity of khasianine was greatly diminished. Nevertheless, only solamargine could induced "sub-G1" of apoptotic feature in flowcytometry. Thus, the 2'Rha moiety of solamargine may play a crucial role in triggering cell death by apoptosis. In addition, the molecular modeling of solamargine indicated that the 2'Rha moiety was adjacent to the rigid steroid structure, and drastically changed the dihedral angle of the glycosidic bond. The regulations of TNFR I and II expression by different carbohydrate moieties were also distinct. It implied that the carbohydrate moieties of steroidal alkaloids might alter the binding specificity to steroid receptors and consequently regulate the gene expression in different manners.
    Biochemical and Biophysical Research Communications 02/1998; 242(1):21-5. · 2.48 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

1,2-orthoester-α-L-rhamnose pyrazine 17b
 
2,3,4-tri-O-acetyl-α-L-rhamnose iodide
 
Bis-steroidal pyrazine 10
 
bis-steroidal pyrazines
 
boron triflouride etherate
 
cancer cell growth
 
human cancer cell line panel
 
murine
 
nosocomial pathogen Enterococcus faecalis
 
pyrazine 10
 
Pyrazine 9 inhibited growth
 
steroidal pyrazine 10
 

George R Pettit