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An application of aminoacetaldehyde dialkoxy acetal to introduce an amino fuctionality in the 6 and/or 11 position of the naphthacenetrione ring system, resulting in key intermediates to aminated anthracyclines, is described.

Two new procedures are described for the preparation of di- and tetra-deuterated 10-[[3-[4-(2-hydroxyethyl)-1-piperazinyl]propyl]]-2-trifluoromethyl-10H-phenothiazine (fluphenazine). Deuterium was introduced in either the 1- or the 1- and 3-positions of the propyl side chain by reduction with deuterated borane in tetrahydrofuran of the appropriately substituted N-10 amide or amido ester. The isotopic purity of the synthesized deuterated products was greater than 99%.

The results of adiabatic compressibility measurements for two copolymers, acrylic acid-vinyl pyrrolidone (AA—VP) and N-dimethylaminoethyl methacrylate-vinyl pyrrolidone (DAM—VP), in three different solvents, namely, water, methanol, and dioxane, have been described. The molecular weight of copolymers was determined by the light scattering method and the IR and NMR spectra of the polymers and copolymers were examined to establish that the alternating acrylic acid–vinyl pyrrolidone and N-dimethylaminoethyl methacrylate–vinyl pyrrolidone structure exists in the copolymers. The AA—VP copolymer behaves as a slightly weaker acid than the homopolymer of acrylic acid, while DAM—VP copolymer is very feebly basic and has the same strength as that of the homopolymer of N-dimethylaminoethyl methacrylate. The reduced viscosity for the two copolymers in aqueous solution is very low (∼0.08 dL/g for AA—VP copolymer). In methanol solution AA—VP and DAM—VP copolymers show a decrease of oK°2 and oV°2 by 61.6 × 10−4 cc/bar/mol and 8.0 cc/mol, and 191.0 × 10−4 cc/bar/mol and 20.0 cc/mol, respectively, over that of the values of aqueous solution. The void space around the solute is smaller in methanol than in water, and accordingly this decrease has been attributed to geometric effect. Only one copolymer, DAM—VP is soluble in dioxane, and the values are seen to have increased in this solution by 71.0 × 10−4 cc/bar/mol and 18.7 cc/mol, respectively, compared to the values obtained from aqueous solution. The experimentally determined oK°2 and oV°2 for AA—VP and DAM—VP copolymer are 0.6 × 10−4 cc/bar/mol, and 102.4 cc/mol and −61.0 × 10−4 cc/bar/mol, 94.4 cc/mol, respectively, in aqueous solution, and −12.0 × 10−4 cc/bar/mol, 211.0 cc/mol and −203.0 × 10−4 cc/bar/mol, 191.0 cc/mol, respectively, in methanol solution. In dioxane solution the values for DAM—VP copolymer are 59.0 × 10−4 cc/bar/mol and 229.7 cc/mol, respectively. These experimentally determined values for AA—VP copolymer show an increase by 0.04 × 10−4 cc/bar/mol, 4.4 cc/mol and 28.3 × 10−4 cc/bar/mol, 8.0 cc/mol in aqueous and methanol solution, respectively, compared to calculated values determined on the basis of no interaction between acid and the pyrrolidone group. In contrast, the DAM—VP copolymer shows a decrease of 27.6 × 10−4 cc/bar/mol and 10.3 cc/mol, 149.3 × 10−4 cc/bar/mol and 20.2 cc/mol, and 23.0 × 10−4 cc/bar/mol and 4.1 cc/mol in aqueous, methanol, and dioxane solutions, respectively. In aqueous solution these differences between calculated and observed values have been attributed to a change of water structure around the copolymer chain. A similar effect is responsible for the difference of the values in the methanol solution also. In the dioxane solution the difference is rather small, and the solvent structure has probably not altered much due to the presence of the DAM unit in the chain.

The adiabatic compressibility of two ionic polymers; namely, poly(acrylic acid) (PAA) and poly(N-dimethylaminoethyl methacrylate) (PDAM) in methanol and dioxane solutions and of a nonionic polymer, poly(vinyl pyrrolidone) (PVP) in aqueous, methanol, and dioxane solutions has been studied. The φV2 and φK2 values for the three polymers and their corresponding monomers in methanol and dioxane solutions are found to be concentration independent. There is a marked difference in φK02 and φV02 values between monomer and polymer in all three solvents. In aqueous solution, the difference in φV02 is, on an average, 16.1 cm3/mol, while in methanol and dioxane solution, the same is 24.0 and 20.5 cm3/mol (average), respectively. All three monomers in dilute aqueous solution show a contraction of volume and decrease of adiabatic compressibility which are comparatively small in methanol and dioxane solutions. The φV02 for PAA, PDAM, and PVP were found to have increased by 0.8, 11.0, and 1.5 cm3/mol, respectively, in dioxane solution over that of the value of the aqueous solution. It is interesting to note that in methanol solution, PAA, PDAM, and PVP show a decrease of φK02 and φV02 values by 68.8 cm3/bar/mol and 8.2 cm3/bar/mol, 32.7 cm3/bar/mol, and 4.3 cm3/mol, and 36.6 cm3/bar/mol and 5.8 cm3/mol, respectively, compared to the values obtained from aqueous solution. This has been ascribed to geometric effect since the void space around the molecules is smaller in methanol than in water.

A series of anthraquinonyl glucosaminosides (10a-e) were synthesized by Koenigs-Knorr glycosidation of the corresponding aglycones (11a-e) with bromo sugar 12 followed by saponification. These glycosides were intended to serve as models to study the role played by the hydroxyl substituents on the aglycone portion of the antitumor anthracycline antibiotics. Superoxide generation as measured in rat heart sarcosomes was found to increase with the addition of successive hydroxyl groups to the anthraquinone nucleus. The 1,8-dihydroxy pattern was determined to generate significantly less superoxide than the 1,4-dihydroxy pattern. Hydroxyl substitution was also observed to stabilize the complex formed between the anthraquinones and DNA and was required for antibacterial activity against a number of Gram-positive organisms.