Synthesis and Biological Activity of Enantiomeric Pairs of Phosphosulfonate Herbicides

The phosphosulfonates are a new class of soil-active herbicides which control a variety of annual grass and broadleaf weeds. Chirality at the phosphorus atom afforded the opportunity to explore stereospecific requirements for herbicidal activity. Chiral (hydroxymethyl)phosphinate intermediates were enzymatically resolved (Pseudomonas fluorescens lipase) from the racemic mixtures and then used to prepare two pairs of enantiomeric phosphosulfonates. Biological testing of the enantiomeric phosphosulfonate herbicides demonstrated that, in each case, the herbicidal activity was attributed to the (+) enantiomer and that the (+) enantiomer is more active than the racemate. Keywords: Phosphosulfonate; herbicide; enantiomer; resolution; lipas

Substituted Tetrahydropyrrolo[2,1-<i>b</i>]oxazol-5(6<i>H</i>)-ones and Tetrahydropyrrolo[2,1-<i>b</i>]thiazol-5(6<i>H</i>)-ones as Hypoglycemic Agents

A series of substituted tetrahydropyrrolo[2,1-b]oxazol-5(6H)-ones and tetrahydropyrrolo[2,1-b]thiazol-5(6H)-ones was synthesized from amino alcohols or amino thiols and keto acids. A pharmacological model based on the results obtained with these compounds led to the synthesis and evaluation of a series of isoxazoles and other monocyclic compounds. These were evaluated for their ability to enhance glucose utilization in cultured L6 myocytes. The in vivo hypoglycemic efficacy and potency of these compounds were evaluated in a model of type 2 diabetes mellitus (non-insulin-dependent diabetes mellitus), the ob/ob mouse. 25a(2S) (SDZ PGU 693) was selected for further pharmacological studies