Patent number: 5200513
Abstract: To produce doxorubicin and its analogues methyl 3alpha, 5alpha-dihydroxy-5beta-(trimethylsilylethynyl)-2alpha-nitromethylcyclohexa ne-1beta-carboxylate acetonide is condensed with 1,4-dihydro-4,4,5-trimethoxy-1-oxonaphthalene in the presence of 1,8-diazabicyclo-[5.4.0]undec-7-ene in an aprotic solvent to produce 3-[ (2beta-carbomethoxy-4beta-ethynyl-4alpha, 6alpha-(di-O-isopropylidenyl)cyclohexanyl-1-yl]-nitromethyl-4,4,5-trimetho xy-1-oxo-1,2,3,4-tetrahydronaphthalene; which is cyclized to produce 9beta-ethynyl-12-hydroxy-7alpha,9alpha-(di-O-isopropylidenyl)-6-nitro-4,5, 5-trimethoxy-5,5a,6,6a,7,8,9,10,10a,11-decahydro -11-naphthacenone. The decahydro-11-naphthacenone is converted to 7alpha-9alpha,(di-O-isopropyl-idenyl)-4,5-dimethoxy-9beta-ethynyl-12-hydro xy-6-nitro-6,6a,7,8,9,10,10a,11-octahydro-11, -naphthacenone.
Type:
Grant
Filed:
June 22, 1990
Date of Patent:
April 6, 1993
Assignee:
Board of Regents, University of Nebraska-Lincoln
Inventor:
Desmond M. S. Wheeler