The Cephalostatins. 21. Synthesis of Bis-steroidal Pyrazine Rhamnosides

Department of Chemistry and Biochemistry, Arizona State University, PO Box 871604, Tempe, Arizona 85287-1604, United States.
Journal of Natural Products (Impact Factor: 3.8). 09/2011; 74(9):1922-30. DOI: 10.1021/np200411p
Source: PubMed


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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