The preparation of zaragozic acid A analogues by directed biosynthesis.

The biosynthesis of steroids and triterpenoids

“…Investigators have probed the effects of chemically modifying both the core 279-290 and the C-6/C-1 side-chains [291][292][293][294] on inhibitory activities of ZGAs (directed biosynthesis has also been employed to obtain side-chain modified analogues). [295][296][297] Monocyclic analogues prepared by cleavage of the ZGA bicyclic core 298,299 and by total synthesis 300 are also described (acyclic mimics of ZGA 301 and alkyl citrates incorporating ZGA-A and -B side-chains 302 have moderate biological activity). Synthesis of a zaragozic acid-PSPP hybrid has been described.…”

Antifungal antibiotics

“…Some other target sites have also proved to be successful in the case of synthetic antifungal compounds. These include ergosterol synthesis inhibitors (like zaragozic acid; Chen et al 1994) inhibitors of DNA function and topoisomerases (like pentamidine), inhibitors of amino acid synthesis (like cispentacin) and microtubule inhibitors (like benomyl;Jones et al 1990;Iwasaki 1993). Attempts have also begun to exploit all these targets to obtain novel antifungal compounds.…”

Antifungal agents: chemotherapeutic targets and immunologic strategies

“…Nevertheless, inhibitors of hydroxymethylglutaryl coenzyme A (CoA) and mevalonic acid synthesis are potential or commercial cholesterol-lowering agents, suggesting that enzymes at the branch points of the sterol pathway may have different affinities for substrates, sparing critical but quantitative minor pathways during depletion of key intermediates (200). Inhibitors of squalene synthase, the squalestatins and zaragosic acids, have also been reported (50,60), although none has promising antifungal activity, probably because of membrane permeability constraints.…”