4235-32-9Relevant academic research and scientific papers
Synthesis and biological activity of unsymmetrical bis-steroidal pyrazines related to the cytotoxic marine natural product cephalostatin 1
Heathcock,Smith
, p. 6828 - 6839 (2007/10/02)
A mild, high-yielding synthesis of symmetrical steroidal pyrazines was achieved from the dimerization of 2-amino-3-ketosteroids, which were produced in situ from the triphenylphosphine-water reduction of the corresponding α-azido ketone. 2-Azidocholestan-3-one gave the dimeric steroidal pyrrazine very cleanly, and two known dimeric pyrazines based on androstanone were also made using this methodology. Both C2-symmetric geometric isomers of the dimeric steroidal pyrrazine derived from cholestane were prepared by reaction of 2,3-diaminocholestane with cholestane-2,3-dione. A route to unsymmetrical bis-steroidal pyrazines was based on the observation that α-acetoxy ketones react with α-amino oximes directly with no need for oxidation of intermediate dihydropyrazines. Heating either 2β,17β-dihydroxyandrostan-3-one diacetate or 2β,17β-dihydroxyhecogenin-3-one diacetate with 2-amino-3-methoxyiminocholestane in toluene at 145°C gave the corresponding unsymmetrical pyrazine in moderate yield. Five of the steroidal pyrazines were evaluated in the National Cancer Institute's new in vitro, disease-oriented antitumor screen, but none showed sufficient activity to warrant in vivo investigation.
