title: The cephalostatins. 21. Synthesis of bis-steroidal pyrazine rhamnosides (1).
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.
authors: Department of Chemistry and Biochemistry, Arizona State University, PO Box 871604, Tempe, Arizona 85287-1604, United States.
authors: George R
authors: GR
authors: Pettit
authors: Ricardo F
authors: RF
authors: Mendonça
authors: John C
authors: JC
authors: Knight
authors: Robin K
authors: RK
authors: Pettit
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001880:Boranes / Q000737:chemistry; D002301:Cardiac Glycosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013293:Enterococcus faecalis / Q000187:drug effects*; D006031:Glycosylation; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010619:Phenazines / Q000737:chemistry*; D011719:Pyrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012210:Rhamnose / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013141:Spiro Compounds / Q000737:chemistry*; D013256:Steroids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D001880:Boranes; D002301:Cardiac Glycosides; D010619:Phenazines; D011719:Pyrazines; D013141:Spiro Compounds; D013256:Steroids; C454806:cephalostatin I; C101707:boron trifluoride etherate; D012210:Rhamnose