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A series of ristocetin analogues with modifications (OH, C=O, C=NOH, NCOCH3) at the C-1' amino group was synthesized and found to possess antibacterial activity against gram-positive bacteria and to bind to Ac2-Lys-D-Ala-D-Ala, a model for the antibiotic's site of action. Due to the lack of a positively charged amino group, the active analogues could not form a salt bridge, indicating that an electrostatic interaction between the positively charged 1'-amino group of ristocetin and the carboxylate anion of the peptide is not required for complex formation. The only compound that did not exhibit good antibacterial activity was epiristocetin aglycone (an analogue with the 1'amino group in the opposite configuration (S) as ristocetin). On the basis of NMR studies of epiristocetin aglycone in solution, the 1'-amino group is located in the proposed carboxylate binding pocket and may sterically block complex formation.

The synthesis of monoesters (P and C) of phosphonoacetic acid (PA) is given. The carboxyl esters were prepared by two methods: the reaction of chloroacetates with tris(trimethylsilyl) phosphite, followed by hydrolysis; and by the acid-catalyzed esterification of PA with the appropriate alcohol. P-Monoesters of PA were prepared either by the reaction of alkyl[bis(trimethylsilyl)] phosphite with benzyl chloroacetate followed by deprotection or by the reaction of dimethylphenyl phosphite with benzyl bromoacetate followed by hydrogenolysis. Three aryl- (alkyl-)phosphinic acid derivatives are reported. The above compounds were evaluated for anti-herpes activity against HSV-induced DNA polymerase and in animals infected with herpes dermatitis.

The preparation and activity against Plasmodium berghei of derivatives of 1-(4-methoxycinnamoyl)-4-(5-phenyl-4-oxo-2-oxazolin-2-yl)piperazine are described. Replacement of the cinnamoyl group was accomplished by acylation or alkylation of 1-(5-phenyl-4-oxo-2-oxazolin-2-yl)piperazine. Modifications of the 5-phenyl group were prepared either by a sequence of reactions involving mandelic ester-pemoline-piperazine pemoline or by the reaction of 5-aryl-2-thio-2,4-oxazolidinedione with piperazine or N-substituted piperazines. In a similar manner, pemoline was allowed to react with N-arylpiperazine, hexahydro-1H-1,4-diazepine, and 2,6-dimethylpiperazine to provide N-arylpiperazine pemoline derivatives and variations in the piperazine moiety. Several compounds in which the 2-oxazolin-4-one ring was replaced with other heterocyclic rings were prepared as were several open-chain analogs. Five compounds (three of them substituted in the para position of the 5-phenyl group and two N-arylpiperazine pemoline derivatives) were found to be active against Plasmodium berghei. The remaining active compound possessed changes in the cinnamoyl group and substitution on the 5-phenyl group.