A number of mesoionic 2-alkylthiothiazol-4-ones (6) were prepared by alkylation of rhodanines or by the reaction of a-bromomalonates with dithiocarbamates. The photolysis of these mesoionic compounds proceeds via a highly strained, bicyclic, ring contraction product which rearranges to a thiazolin-2-one (1 4). loses sulphur, affording a p-aminoacrylate (1 l ) , or is trapped by methanol giving methoxy-p-lactams (1 2) and (1 3). THE photochemistry of certain classes of five-membered mesoionic heterocycle has been generally rationalized in terms of a mechanism which involves a transient fourmembered carbonyl-containing ring 1, formed by photolytically induced ring contraction (Scheme 1). This process presents an attractive possibility for p-lactam synthesis from mesoionic thiazolones, imidazolones, or oxazolones.New syntheses of p-lactams are always designed with a view to their application in the synthesis of penicillins and cephalosporins. This requires a polyfunctional precursor. Accordingly the known 2-alkylthiothiazolium-4-olates (Scheme 2), having the alkylthio-group in the desired position, were considered to be good models for a photolytically induced cephalosporin or penicillin synthesis.The appropriate substituent on C-5 of the mesoion would be an amido-group. However, all attempts up to now to prepare amido-substituted mesoionic thiazolones of type (6) have failed.Since the conversion of carboxy-p-lactams into aminop-lactams has been de~cribed,~ another useful substituent in position 5 would be a carboxy-group. We were, in
In spite of considerable efforts by many workers, there has been a lack of progress in the area of amine fungicides since fenpropimorph. Random synthesis of a large variety of different amine compounds, as well as intelligent structural modification of the lead structure fenpropimorph (well over 15 000 amines have been screened at BASF alone) have not led to a new market product so far. Further work has been focused on the reported mode of action of fenpropimorph, notably on the inhibition of the sterol Δ14‐reductase. Although some doubt has to be cast on the hypothesis that fenpropimorph behaves as a sterol mimic, the concept of ‘high energy intermediate’ inhibitors has been employed successfully. Rational drug design of azasterol mimics has led to a number of very potent inhibitors of the sterol Δ14‐reductase which also displayed high fungicidal activity in the greenhouse. Although many of these compounds are more powerful reductase inhibitors than fenpropimorph, under field conditions none showed significant advantages over this established fungicide.
Most likely, fenpropimorph already exhibits the maximum fungicidal activity which can be attained by blocking the sterol Δ14‐reductase. This would mean that, with the development of the ‘second generation’ amine fungicide fenpropimorph, this class of compounds has already virtually been optimized.
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