Wasimul Haque

Heteroanthracyclines. III: 6,7,11-tri-O-methyl-4-demethoxy-12-sulfonodaunomycinone [6,10,11-trimethoxy-8-hydroxy-8-acetyl-7,8,9,10-tetrahydrobenzo(B)-thioxanthen-12-one-5-dioxide]

Abstract The sulfone analogue of 6,7,11-tri-O-methyl-4-demethoxydaunomyacinone, namely 6,7,11-tri-O-methyl-4-demethoxy-12-sulfonodaunomycinone ( 12 ) was synthesized using 5,8-dimethoxy-2-acetyltetralin ( 13 ) as starting material which can be prepared in large scale by hydrogen chloride catalysed cyclization of 3- (2,5-dimethoxybenzyl)-l,4-dioxopent shortening and simplifying our earlier procedures and eliminating the handling of large quantity of liquid hydrogen fluoride. The intermediate 15 can be easily prepared in large scale according to the procedure which we reported earlier. 13c Reaction of 13 with 2,2-dithiosalicylic acid gave an isomeric mixture of 17 and 18 which were separated and their structure differentiated by dipole moment studies 14 Isomer 17 was reduced by Zn dust to 22 and 23 which reacted with anhydrous methanol to form 24 and 25 . Both 24 and 25 as an isomeric mixture were oxidized to 28 and 29 by oxygen in basic N,N-dimethylformamide solution and finally to the stable sulfones 30 and 31 by m -chloroperoxybenzoic acid. These two isomeric sulfones were separated and fully characterized and then oxidized further to form 34 which was converted to the title compound 12 by free radical bromination and reaction with anhydrous methanol in the presence of silver trifluoromethanesulfonate. The structure of 12 was positively established by detailed analysis of its high field PMR spectrum (Fig. 1)

A Convenient Hydroxylation

Abstract In connection with the introduction of hydroxy functions to the C-7 and C-9 positions of anthracycline antitumor antibiotics, 3 such as 4-demethoxydaunomycin (1)3 and of the hetero-anthracyclines such as 4-demethoxy xanthodaunomycin (2), 4-demethoxy thioxantho-daunomycin (3) and 4-demethoxy sulfoxodaunomycin (4), we have discovered that for the hetero-anthracycline series4 the dihydroxylation can be done in one step instead of a multi-step sequence as in the anthracycline series5. However, in the case of hetero-iso-anthracycline series4, ring D was aromatized under the same dihydroxylation condition. Thus, in a typical experiment, xanthone (5) (1.3 g) was added to a solution of anhydrous N,N-dimethylformamide (150 ml) and t-butyl alcohol (30 ml).