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Commercially available fish oils with n−3 fatty acid contents ranging from 29 to 34% were converted enzymically, with Amano P lipase, to mixtures of glycerides with n−3 fatty acid contents ofca. 50%, in weight recovery yields of 23–50%, depending upon extraction procedures. Glyceride mixtures with n−3 fatty acid contents above 70% were obtained in yields of 14–21%. The processes are based on the relative stability of the ester linkages that involve n−3-fatty acyl groups and the regioselectivity of the enzyme toward acyl groups at the 1,3-positions of glycerol.

An alternative synthesis of 7-chloro- N -methyl-5-(1 H -pyrrol-2-yl)-3 H -1,4-benzodiazepin-2-amine, the compound that inhibits gene expression by HIV-1 at the level of transcriptional transactivation by Tat, has been developed. The process is based on ring expansion of 6-chloro-2-chloromethyl-4-(1 H -pyrrol-2-yl)quinazoline 3-oxide which leads to the corresponding benzodiazepine Ro24-7429. Quinazoline 3-oxide formation in the presence of boron trifluoride gives a tetracyclic system containing a 2,2-difluoro-1,3,6,2-oxadiazaborine ring that survives ring expansion to 13-chloro-5,5-difluoro-9-(methylamino)-5 H -pyrrolo[1′,2′:3,4]-1,3,6,2-oxadiazabora[6,5- d ]-8 H -1,4-benzodiazepin-7-ium hydroxide inner salt. This unusual benzodiazepine does not significantly inhibit Tat-mediated gene expression by HIV-1.

The preparation and oxidation of 2,3-dihydroindazoles to 1H, 2H or 3H-indazoles is described. A method for the synthesis of indazole 2-oxides has been found. Oxidation of 2-acetyl-2,3-dihydro-3,3-disubstituted indazoles 5a and 5c gave quinoid compounds 20a, 20b, 24a and 24b, which could be isomerized to 3H-indazoles upon removal of the acetyl group. A quinoid compound 21 was also obtained on treatment of 5a with tetracyanoethylene.

A facile synthesis of the 4H-imidazo[5,1-c][1,4]benzothiazine ring system is described. The synthesis utilized the annulation of an imidazole ring onto a 2H-1,4-benzothiazin-3(4H)-one via the addition of the anion of ethyl isocyanoacetate. Methods for the functionalization of the 1-, 3-, 4-, and 5-positions of the ring system are presented.

s-Triazolo[4,3-a][1,4]benzodiazepines bearing various substituents in the 1 position were prepared by oxidative cyclization of the appropriate aldehyde hydrazones of 2-hydrazinobenzodiazepines. Diethyl azodicarboxylate and activated manganese dioxide were used as oxidizing agents. The new triazolo compounds were active in the CNS tests but none of them reached the potency of the known triazolobenzodiazepines.

The reactions of 2-amino-1,3,4-thiadiazole with 1,3-dicarbonyl compounds are described. 2,4-Pentanedione gave 2-thiocyanato-4,6-dimethylpyrimidine while diethylmalonate and ethyl acetoacetate yielded 5-hydroxy-7H-1,3,4-thiadiazolo[3,2-a]pyrimidin-7-one and 7-methyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one, respectively. The structure of the latter compound was confirmed by a synthesis of the alternative isomeric structure (5-methyl-7H-1,3,4-thiadiazolo[3,2-a]pyrirnidin-7-one) from 2-amino-1,3,4-thiadiazole and α-bromocrotonic acid.

The 2-hydrazinobenzodiazepines 1 were reacted with acelylacelone to form the hydroxy-pyrazolines 2 which were converted to the triazolobenzodiazcpines 6 and the 2-pyrazolyl-benzodiazepine 4. Ring cleavage of the hydrazone 8 obtained from cyclohexane-1,3-dione and 1a led similarly to the 1-(4-oxopentyl)triazolol)enzodiazepine 12.

s-Triazolo[4,3-a][1,4]benzodiazepines bearing various substituents in the 1 position were prepared by oxidative cyclization of the appropriate aldehyde hydrazones of 2-hydrazinobenzodiazepines. Diethyl azodicarboxylate and activated manganese dioxide were used as oxidizing agents. The new triazolo compounds were active in the CNS tests but none of them reached the potency of the known triazolobenzodiazepines.

7-Nitro-substituted benzodiazepines were reduced with stannous chloride in a buffered system to the corresponding 7-hydroxyamino derivatives. These compounds were alkylated, acylated, and converted to nitroso and azoxy derivatives. The rearrangement of a hydroxyamine to an aminophenol and its oxidation to an aminoquinone are also exemplified. The results of the pharmacological screening for CNS effects are given.

Base catalyzed cyclization of the 2-methylazoxybenzophenone (4B) obtained by condensation of the 2-nitrosobenzophenone (2a) with methylhydroxylamine led to the cinnoline 2-oxide (7) which is the major product of the peracid oxidation of the corresponding cinnoline (5).

2,4-Benzodiazepines can be prepared by condensation of an activated 2-benzoylbenzoic acid with 2-(aminomelhyl)phthalimide. A synthesis of this reagent is described.