Polyunsaturated macrolactone

Antibiotics of the streptogramin family are an association of two groups of molecules the group A components are polyunsaturated macrolactones and the group B components are peptidic macrolactones (depsipeptides). The different members of each group differ in some substituents, functional moieties or amino-acid residues (see Sects. 4.1 and 5.1). 

Natural pristinamycin II is a mixture of two polyunsaturated macrolactones which differ in the level of oxidation of the proline residue. The major component, pristinamycin 11 (33), possesses a dehydroproline ring, which is replaced by a (i )-proline residue in the minor component, pristinamycin Ilg (34). The ratio of these two compounds in the natural mixture varies from 90 10 to 97 3 depending on the fermentation conditions and the strain of Streptomyces. The pristinamycin II components also contain an oxazole nucleus incorporated into the macrolactone structure, which is relatively uncommon in naturally occurring compounds. 

A formal total synthesis of oximidine II was achieved by G.A. Molander et al., using an intramoiecuiar Suzuki-type cross-coupiing between an alkenyl potassium trifluoroborate and an alkenyl bromide to construct the highly strained, polyunsaturated 12-membered macrolactone core of the natural product. " The stability of potassium trifluoroborates was exploited in order to establish the best conditions for the macrocyclization. 

Hofle et al. [88] first isolated archazolide 111 from the myxobacterium Archangium gephyra. This compound exhibited potent growth-inhibitory activity against a number of murine and human cancer cell lines, based on selective inhibition of vacuolar-type ATPases, in vitro and in vivo. It comprises unique structure with a polyunsaturated 24-membered macrolactone, with eight stereogenic centers and a pendant thiazole side chain at C23. 

The Mediterranean species Aplysia depilans harvested in Spain preferentially consumes the green alga Ulva lactuca, and stores in its skin a series of 16- and 17-membered macrolactones derived from polyunsaturated adds with 16 or 18 carbon atoms and bearing a hydroxyl group at position 15 or 16. Aplyolides A-E are aU idithyotoxic (Spinella et al, 1997a). 

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