The interaction specificity of salmon sperm DNA with various derivatives of daunorubicin has been studied. The results of binding, viscometric, 1H nuclear magnetic resonance (NMR), flow dichroism, DNA template inhibition, rates of dissociation, and circular dichroism studies are found to be consistent with an intercalation mode of binding of the anthracycline ring as has been shown by other investigators. Moreover, it is observed that (i) strength of binding, (ii) the ease of dissociation of DNA-anthracycline complexes, and (iii) the degree of inhibition of the DNA-dependent RNA polymerase are dependent on the presence of the amino sugar moiety of daunoseamine. The results are consistent with specific H bonding of the amino group of the sugar moiety with DNA as has been suggested earlier by Pigram et al. (Pigram, W.J., Fuller, W., and Hamilton, L.D. (1972), Nature (London), New Biol. 235, 17). Peptide derivatives substituted at the amino sugar function of daunorubicin lower the affinity of the drug to DNA and presumably interfere with the "full insertion" of the anthracycline drugs between base pairs of DNA. The significance of these findings in relation to the biological efficacy of daunorubicin and related derivatives as antileukemic agents is discussed.

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74, 219 (1974)). Several small vpc peaks (ca. 2-4% of the total) were trapped and examined: since 28 was not present, it was assumed that they were diastereomers of 23 and 24 in which the cyclizing side chain had epimerlzed, e.g.

Canthiphytine (5) from Haplophytine. To a solution of haplo-phytine (132 mg) in dilute hydrochloric acid (3 ml, 12%) was added zinc dust (250 mg), and the mixture was refluxed under nitrogen for 1 hr. The mixture was left overnight. The clear pale brown solution was cooled in an ice bath, basified with ammonia, and extracted with ether. The washed and dried ether layer was concentrated and the dark residue (60 mg) was treated with methanolic hydrogen chloride. The gummy solid was crystallized from acetone-methanol to give 7 mg of canthiphytine hydrochloride: mp 302°dec; m/e 256.1211 (M+ 256.1212); m/e 257 (14), 256(82), 255 (37), 239 (12), 214 (17), 213 (100), 201 (5), 200 (30), 199 (20). 186 (5), 185 (30), 184 (32), 183 (4), 172 (4), 171 (9), 170 (5), 166 (3). This material was identical (mixture melting point and ir spectrum in KBr) with the hydrochloride of synthetic 5. Supplementary Material Available. Elemental analyses for the indicated compounds will appear following these pages in the microfilm edition of this volume of the journal. Photocopies of the supplementary material from this paper only or microfiche (105 X 148 mm, 20X reduction, negatives) containing all of the supplementary material for the papers in this issue may be obtained from