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Several potentially bis(alkylating) bis(quinones) (3-5) and 1,4- and 1,3-bis(alkylating) monoquinones (6-13) belonging to general structure 2,2'-ethylenebis[5-[(leaving group)methyl]-1,4-benzoquinone] (3-5) and 2,5- and 2,6-bis[(leaving group)methyl]-1,4-benzoquinone water-soluble and -insoluble classes were prepared by oxidative demethylation of the corresponding tetramethoxydiphenylethanes (17-19) and dimethoxybenzenes (24, 27, 36-39), respectively. Methods employed for the preparation of tetramethoxydiphenylethane intermediates involved (1) arylmethyl bromide coupling and (2) catalytic hydrogenation of stilbene intermediates derived via Wittig reaction of (arylmethyl)phosphonium salts with aryl aldehydes. However, in biological investigations using a subcutaneous B16 (hypoxic) melanoma tumor in BDF1 hybrid mice with cyclophosphamide as positive control the most interesting series of structurally related analogues were the potentially monoalkylating monoquinones of the 2-[(leaving group)methyl]-1,4-benzoquinone type (i.e., 14 and 15) having water-insoluble (acetoxy) and water-solubilizing (succinate) groups. Serial measurements of tumor size, and evaluation of increased life span, in response to drug treatment also revealed potentially 1,4-bis(alkylating) (bromomethyl)-1,4-quinone 7 and 1,3-bis(alkylating) (hydroxymethyl)-1,4-quinone 10 to have variable activity, but none of the potentially bis(alkylating) bis(quinones) showed antitumor properties in this model.

Stereocontrolled syntheses for the six diastereomeric 1,2-dihydroxy-4,5-diaminocyclohexanes 3a-f from cyclohexene diamines cis-4 and trans-5 are described. Cbz-protected species cis-9 and trans-11, respectively, served as a source of stable Cbz-protected precursors to these cyclohexanediol diamines (CDD), which were liberated upon catalytic (H2, Pd/C) hydrogenation. Catalytic osmylation of 9 afforded a mixture of diastereomeric diols 13 and 14, which served as precursors to cis-anti-cis CDD 3b and cis-syn-cis CDD 3a, respectively, whereas osmylation of 11 yielded the expected single product 12, the precursor to cis-anti-trans CDD 3d. Epoxidation of olefins 9 and 11 afforded oxiranes 15 and 17, respectively, which upon acid-catalyzed hydrolysis produced the corresponding Cbz-protected diols 16 and 18, which served as precursors to CDD trans-anti-cis 3c, and trans-anti-trans 3e. Formation of diol 18 from oxirane 17 was accompanied by formation of 2-oxa-4-azabicyclo[3.3.1]nonan-3-one 19. CDD trans-syn-trans 3f was prepared from diol 12 via regioselective monoacetylation, yielding 22, followed by oxidation to afford ketone 24. Sodium borohydride reduction and acetylation produced diacetate precursor 26. PtIICl2 complexes of five of the diamines (3a-d,f) are described, and their activities were compared with cisplatin (1) by employing P-388 leukemia implanted CDF1 mice. The data indicate that stereochemistry of the amino groups on the cyclohexanediamine ligand modulate the expression of toxic effects, and depending upon hydroxyl and amino group stereochemistry, there is a marked effect on complex formation (e.g., Cl2PtII-3e) and solubility characteristics (e.g., Cl2PtII-3c). Acetylation of the hydroxyl functions in selected isomers (28a-c) rendered the PtII complexes inactive. A single-crystal X-ray structure of compound 3a was determined at room temperature and indicated the cis-syn-cis arrangement of the OH and NH2 groups.

An indirect fluorescent antibody (FA) staining technique was developed for the rapid detection of Thiobacillus ferrooxidans. The specificity of the FA stain for T. ferrooxidans was demonstrated with both laboratory and environmental samples. Coal refuse examined by scanning electron microscopy exhibited a rough, porous surface, which was characteristically covered by water-soluble crystals. Significant numbers of T. ferrooxidans were detected on the exterior refuse surface by FA staining, whereas none were detected in the refuse pores. A positive correlation between numbers of T. ferrooxidans and acid production in coal refuse in the laboratory was demonstrated with the FA technique.

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