Verfahren zur Herstellung von Cumarinderivaten

1,253,286. 3 - Amido - 7 - (pyrrolylcarbonyl) noviosylcoumarins. BRISTOL-MYERS CO. 21 April, 1969 [29 April, 1968], No. 20176/69. Headings C2A and C2C. Novel compounds of the formula (II) where R is H or CH 3 , and X is a group of the formula or -C m H 2m-1 in which n is an integer of 1 to 21, m is an integer of 2 to 21, R1 and R2 are alike or different and denote H, cyclohexyl or R3, R4- substituted-phenyl, R3 and R4 being alike or different and denoting H, F, Cl, Br, I, CF 3 , -NH 2 , NO 2 , N,N-di(C 1-8 alkyl)amino, CN, C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 1-8 alkoxy, -OH, -COOH, -COO-C 1-8 alkyl -OCOCH 3 , -SH, -S-C 1-8 alkyl or -SCOCH 3 , may be obtained (a) by reacting a di, tri or tetratetrahydropyranyl coumermycin A 1 or A 2 with an acylating agent XCOZ, where Z is halogen, -OCOX or -OCOC 1-8 alkyl at a temperature from - 25‹ to 150‹ C. in a protonaccepting solvent system to yield an intermediate compound of the formula: which is allowed to stand in a polar solvent with a catalytic amount of an acid at a temperature above 0‹ C. to cleave the tetrahydropyranyl ether linkage, or (b) by reacting a compound of the formula (IX): with an acylating agent XCOHal in pyridine solution. The preparation of intermediates is described as follows: monosodium coumermycin A 1 is reacted with benzylchloroformate to yield biscarbo-benzoximido-coumermycin A 1 which is treated with HCl to yield 3-carbobenzoxamido-4- hydroxy-8-methyl-7-[3-0-(5-methyl-2-pyrrolylcar - bonyl)-noviosyloxy]coumarin and this is hydrogenolyzed to 3-amino-4-hydroxy-8-methyl-7-[3 0-(5-methyl-2-pyrrolylcarbonyl)noviosyloxy] coumarin (IX). Pharmaceutical compositions effective against diseases caused by Gram-positive and some Gram-negative bacteria comprise compounds of the formula II above together with a diluent or carrier.