合成路线:By condensation of (S)-N-[2-[1-(chloromethyl)-5-hydroxy-8-methyl-1,2,3,6-tetrahydrobenzo [1,2-b:4,3-b']dipyrrol-3-ylcarbonyl]-1H-indol-5-yl]-6-(diethylamino) benzofuran-2-carboxamide (I) with phenyl isocyanate (II) by means of triethylamine in THF.
参考文献标题:Carzelesin
文献作者:Mealy,N.; Castar,J.
参考来源:Drugs Fut 1996,21(3),245
合成路线:The reaction of indoline (I) with propynoic acid methyl ester (II) in methanol gives the acrylic acid derivative (III),which is cyclized by means of Pd(OAc)2 in DMA to yield the pyrroloindole (IV).The reduction of the ester group of (IV) by means of BH3/Me2S in refluxing THF affords intermediate (V),which is treated with CCl4 and PPh3 to provide the chloromethyl derivative (VI).The O-deprotection in (VI) by means of HCOONH4 and Pd/C in THF gives the hydroxy compound (VII),which is N-deprotected by means of HCl in ethyl acetate to yield the pyrroloindole (VIII).The condensation of (VIII) with the known indole carboxylic acid (IX) by means of EDC in DMF affords the carboxamide (X),which is treated with phenyl isocyanate (XI) and TEA in THF to provide the target Carzelesin.
合成路线:The intermediate pyrroloindole (VIII) was prepared from the previously reported (S)-aminoindoline (I).Michael addition of methyl propiolate (II) to aminoindoline (I) in MeOH provided the aminoacrylate (IIIa-b).Oxidative cyclization of (IIIa-b) was effected with Pd(OAc)2 in DMA to afford the 3-(methoxycarbonyl)pyrroloindole (IV).Simultaneous reduction of both the methyl ester and acetate groups of (IV) with borane-dimethyl sulfide complex gave rise to alcohol (V).Chlorination of (V) to give the chloromethyl derivative (VI) was carried out by treatment with triphenylphosphine and carbon tetrachloride.The O-benzyl protecting group of (VI) was subsequently removed by transfer hydrogenolysis yielding phenol (VII).The N-Boc group of (VII) was then cleaved under acidic conditions to furnish (VIII).
合成路线:Condensation of 5-aminoindole-2-carboxylic acid ethyl ester (IX) with phosgene at very low temperature furnished the N,N'-bis(indolyl)urea (X).Subsequent basic hydrolysis of the ethyl ester groups of (X) gave diacid (XI).This was finally coupled with the intermediate pyrroloindole (VIII) by means of EDC to provide the title diamide.
合成路线:The condensation of indoline (I) with methyl acetoacetate (II) by means of Ts-OH in refluxing benzene gives the adduct (III),which is cyclized by means of Pd(OAc)2 in hot DMA to yield the pyrroloindole (IV).The hydrolysis of the acetate group of (IV) by means of K2CO3 in methanol affords the hydroxymethyl compound (V),which is treated with CCl4 and PPh3 to provide the chloromethyl derivative (VI).The cleavage of the benzyl protecting group of (VI) by means of HCOONH4 and Pd/C in THF gives the hydroxy derivative (VII),which is N-deprotected by means of HCl in ethyl acetate to yield the intermediate (VIII).The condensation of (VIII) with 5,6,7-trimethoxy-1H-indole-2-carboxylic acid (IX) by means of EDC in DMF affords the carboxamide (X),which is treated with DBU in acetonitrile to provide the cyclopropapyrroloindole (XI).The reaction of (XI) with HBr in acetonitrile gives the bromomethyl derivative (XII),which is treated with 4-nitrophenyl chloroformate (XIII) to yield the active carbonate ester (XIV).Finally,this compound is treated with 1-methylpiperazine (XV) to provide the target Pibrozelesin.
参考文献标题:Novel syntheses of optically active CC-1065,U-73,975 (adozelesin),U-80,244 (carzelesin),U-77,779 (bizelesin),KW-2189,and DU-86
文献作者:Fukuda,Y.; et al.
参考来源:Heterocycles 1997,45(12),2303
产品链接: CAS No. 119813-10-4››