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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Boranes / chemistry
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Cardiac Glycosides / chemical synthesis*
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Cardiac Glycosides / chemistry
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Cardiac Glycosides / pharmacology
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Enterococcus faecalis / drug effects*
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Glycosylation
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Humans
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Mice
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Microbial Sensitivity Tests
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Molecular Structure
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Phenazines / chemistry*
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Pyrazines / chemical synthesis*
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Pyrazines / chemistry
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Pyrazines / pharmacology
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Rhamnose / analogs & derivatives
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Rhamnose / chemical synthesis*
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Rhamnose / chemistry
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Rhamnose / pharmacology
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Spiro Compounds / chemistry*
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Steroids / chemical synthesis*
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Steroids / chemistry
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Steroids / pharmacology
Substances
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Antineoplastic Agents
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Boranes
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Cardiac Glycosides
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Phenazines
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Pyrazines
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Spiro Compounds
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Steroids
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cephalostatin I
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boron trifluoride etherate
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Rhamnose