Abstract: 1-N-Alkyl-Aminoglycoside-XK-88 derivatives, valuable as antibacterial agents, are prepared by the reaction of an acid addition salt of the corresponding 1-N-unsubstituted-Aminoglycoside-XK-88 antibacterial derivative or of a 2"-N-alkanoyl-Aminoglycoside-XK-88-5 derivative in an inert solvent, preferably a protic solvent containing water, with one equivalent of a hydride-donor reducing agent and with at least one equivalent of an aldehyde.The 2"-N-alkanoyl-Aminoglycoside-XK-88-5 intermediates are prepared by the reaction of a partially neutralized acid addition salt of Aminoglycoside-XK-88-5 with an acylating agent, and isolating the 2"-N-alkanoyl-Aminoglycoside-XK-88-5.

Abstract: 1-N-Alkyl-4,6-di-(aminoglycosyl)-1,3-diaminocyclitols, valuable as antibacterial agents, are prepared by treating an acid addition salt of a 4,6-di-(aminoglycosyl)-1,3-diamonocyclitol antibacterial agent in an inert solvent, preferably a protic solvent containing water, with one equivalent of a hydride donor reducing agent and with at least one equivalent of an aldehyde.The 1-N-alkyl-4,6-di-(aminoglycosyl)-1,3-diaminocyclitols are also prepared by treating the corresponding 1-N-acyl-4,6-di-(aminoglycosyl)-1,3-diaminocyclitol with an amide-reducing hydride reagent in an inert organic solvent.Other methods of preparing 1-N-alkyl-4,6-di-(aminoglycosyl)-1,3-diaminocyclitols include carrying out the foregoing processes with partially N-protected intermediates. Another useful process involves preparing a Schiff base of the 1-amino function of a partially N-protected 4,6-di-(aminoglycosyl)-1,3-diaminocyclitol followed by reduction of said Schiff base and removal of the N-protecting groups.

Abstract: 5-Epi-4,6-di-O-(aminoglycosyl)-2-deoxystreptamines and 1-N-alkyl-5-epi-4,6-di-O-(aminoglycosyl)-2-deoxystreptamines, valuable as antibacterial agents, are prepared from the corresponding 5-O-hydrocarbonsulfonyl (or substituted hydrocarbonsulfonyl)-4,6-di-O-(aminoglycosyl)-2-deoxystreptamine wherein amino and hydroxyl functions are protected by groups susceptible to reductive cleavage or to basic or mild acid hydrolysis, by the reaction thereof with dimethylformamide at elevated temperatures, followed by removal of the protecting groups.

Abstract: 5-Epi-azido- and 5-epi-amino-4,6-di-O-(aminoglycosyl)-2,5-dideoxystreptamines and 1-N-alkyl derivatives thereof, valuable as antibacterial agents, are prepared from the corresponding 5-O-hydrocarbonsulfonyl (or substituted hydrocarbonsulfonyl)-4,6-di-O-(aminoglycosyl)-2-deoxystreptamine wherein all other hydroxyl functions and all amino functions are protected, by the reaction thereof with an alkali metal azide in an organic solvent followed by the reaction of the resulting 5-epi-azido-4,6-di-O-(aminoglycosyl)-2,5-dideoxystreptamine with base to remove the protecting groups, or with hydrogen in the presence of a catalyst or with an alkali metal in liquid ammonia, and thence cleavage of any remaining hydroxyl and amino protecting groups in the thereby formed 5-epi-amino-4,6-di-O-(aminoglycosyl)-2,5-dideoxystreptamine or 1-N-alkyl derivative thereof.

Abstract: Hydroxylaminoeverninomicins having antibacterial activity are prepared by electrochemically reducing the corresponding everninomicin having a nitro function or the corresponding nitrosoeverninomicin in an aqueous miscible organic solvent under an inert atmosphere or in an anhydrous aprotic solvent in the presence of carbon dioxide. Additionally, nitrosoeverninomicins, upon electrochemical reduction in an aprotic solvent under an inert atmosphere, are converted to the corresponding hydroxylaminoeverninomicins. Preferred starting compounds are everninomicins B, C and D whereby are obtained hydroxylaminoeverninomicins B, C and D, respectively. Particularly useful is the electrochemical reduction of everninomicin D in anhydrous dimethylformamide in the presence of carbon dioxide to obtain hydroxylaminoeverninomicin D of excellent purity in high yields.

Abstract: 1,3,2',3"-tetra-N-acyl-5'-deaminomethyl-5'-formylsisomicin and 1,3,2',3"-tetra-N-acyl-5'-de-.alpha.-aminoethyl-5'-acetylverdamicin are prepared from the 1,3,2',3"-tetra-N-acyl-6'-N-(2,4-dinitrophenyl) derivatives of sisomicin and verdamicin, respectively, by reaction with selenium dioxide. They are useful intermediates in the preparation of 6'-N-alkylsisomicin derivatives and 6'-N-alkylverdamicin derivatives having antibacterial activity.

Abstract: 21-Halogeno-17.alpha.-acyloxy-20-keto-4-pregnenes having physiological properties are prepared by the reaction of a 17.alpha.,21-dihydroxy-20-keto-4-pregnene 17.alpha.,21-orthoester with a halide reagent selected from the group consisting of triarylsilyl halides and tri-lower alkylsilyl halides in an organic solvent, said halide being chloride or bromide. Preferred reagents are tri-lower alkylsilyl halides, particularly trimethylsilyl chloride.

Abstract: Novel retinoic acid esters of anti-inflammatory steroids of the pregnane series are described and their use in the treatment and control of acne vulgaris via the topical or intralesional route. A preferred mode of the invention comprises treating acne by applying topically to the affected area hydrocortisone 21-all-trans-retinoate in concentrations of from about 0.05 to about 0.15 percent. Pharmaceutical formulations and methods for the manufacture of the novel steroidal retinoates are also described.

Abstract: 21-Desoxy-17.alpha.-acyloxy-20-keto-4-pregnenes having physiological properties are prepared by the reaction of a 17.alpha.,21-dihydroxy-20-keto-4-pregnene 17.alpha.,21-orthoester or a 21-iodo-21-desoxy-17.alpha.-acyloxy-20-keto-4-pregnene with an iodide reagent selected from the group consisting of triphenylsilyl iodide, tri-lower alkylsilyl iodide and triphenylmethyl iodide. When said 17.alpha.,21-dihydroxy-20-keto-4-pregnene 17.alpha.,21-orthoester is reacted with less than two molar equivalents of a tri-lower alkylsilyl iodide reagent there is also formed a 21-iodo-21-desoxy-17-.alpha. -acyloxy-20-keto-4-pregnene, a useful intermediate, which, upon reaction with additional iodide reagent, is converted to the corresponding 21-desoxy-17.alpha.-acyloxy-20-keto-4-pregnene.

Abstract: The novel aminoglycoside, 0-2-amino-2,3,4-trideoxy-.alpha.-D-glycero-hex-4-enopyranosyl-(1.fwdarw.4) -garamine, is prepared by treating Aminoglycoside 66-40C with aqueous acid followed by treatment with a hydride donor reducing agent. Pharmaceutical compositions of the novel aminoglycoside and its pharmaceutically acceptable acid addition salts are described as well as their use as antiprotozoal agents.

Abstract: (17R)-Spiro-[androstane-17,1'-cyclobutan]-2'-ones are prepared by the reaction of a 17-oxo androstane, wherein all other ketones are blocked, with a cyclopropylarylsulfide or with a cyclopropylarylsulfonium salt having a non-nucleophilic anion, in an organic solvent together with a strong base, followed by reaction in situ of the intermediate thereby formed with aqueous acid or water.Some (17R)-spiro-[androstan-17,1'-cyclobutan]-2'-ones are useful as intermediates in preparing (17R)-spiro-[3-oxo-4-androstene-17,1'-cyclobutan]-2'-ones which are aldosterone antagonists. Additionally, (17R)-spiro-[androstane-17,1'-cyclobutan]-2'-ones are useful as intermediates in preparing known 17.alpha.-pregnane-21,17.beta.-carbolactones, valuable aldosterone blocking agents.

Abstract: Novel monocyclic macrocyclic compounds having nitrogen bridgehead atoms and having in the hydrocarbon bridging chains at least two additional hetero atoms selected from the group consisting of sulfur, oxygen, and nitrogen, when admixed with a compatible cation-donor compound form stable cation-containing macrocyclic complexes which, in turn, can be conveniently dissociated by addition of acid or a quaternizing agent. The novel macrocyclics are valuable for use in the same way and for the same purposes as chelating agents.

Abstract: Steroidal 6-azido-4,6-pregnadieno[3,2-c]pyrazoles having glucocorticoid activity are prepared by treating a 6-unsubstituted-4,6-pregnadieno[3,2-c]pyrazole with a halogen azide followed by treatment of the thereby formed 6-azido-7-halogeno-6,7-dihydro-4-pregnene[3,2-c]pyrazole with a dehydrohalogenating agent. Other methods of preparing these compounds are described, including the process of treating a 6-azido-17.alpha.,20; 20,21-bismethylenedioxy-4,6-pregnadiene-3-one with an alkyl formate in the presence of base followed by treatment of the resulting 2-hydroxymethylene derivative with a hydrazine or, alternatively, by converting said 2-hydroxymethylene to a 2-alkoxymethylene derivative followed by treatment thereof with a hydrazine.Preferred compounds include 6-azido-11.beta.,17.alpha.,21-trihydroxy-20-keto-4,6-pregnadieno[3,2-c]pyr azoles, particularly 2'-phenyl-9.alpha.-fluoro(and 9.alpha.-chloro)-16-methyl-derivatives thereof which possess potent anti-inflammatory activity.

Abstract: Pharmacologically valuable 3-keto-6-azido-4,6-bis-dehydro-steroids are prepared by treating a 3-keto-6.beta.,7-diacyloxy-4-dehydro-steroid, preferably a 3-keto-6.beta.,7.beta.-diacyloxy-4-dehydrosteroid, wherein said acyloxy group is a good leaving group (e.g. hydrocarbonsulfonyloxy), with an azide salt in a nonreactive organic solvent. Novel intermediates for this process, i.e. novel 3-keto-6.beta.,7.beta.-dihydroxy-4-dehydro-steroids and 6.beta.,7.beta.-dihydrocarbonsulfonyloxy-esters thereof, are conveniently prepared by treating a 3-keto-4,6-bis-dehydro-steroid with osmium tetroxide followed by reductive cleavage of the 6.beta.,7.beta.-osmate ester thereby formed, isolating and thence esterifying the resulting 3-keto-6.beta.,7.beta.-dihydroxy-4-dehydro-steroid with a hydrocarbonsulfonyl halide in a tertiary amine.