Lactones macrolides

The synthesis of five-, six-, and seven-membered cyclic esters or timides uses intramolecular condensations under the same reaction condifions as described for intermolecular reactions. Yields are generally excellent. An example from the colchicine synthesis of E.E. van Ta-melen (1961) is given below. The synthesis of macrocyclic lactones (macrolides) and lactams (n > 8), however, which are of considerable biochemical and pharmacological interest, poses additional problems because of competing intermolecular polymerization reactions (see p. 246ff.). Inconveniently high dilution, which would be necessary to circumvent this side-... 

Dihydropyrenophorin, from Drechslera avenae, is a leaf pathogen of both wild and cultivated oats. It causes reddish brown lesions with a necrotic sunken center. At least one compound isolated from broth cultures of this fungus caused comparable lesions on oats and a variety of other plants at 3.2 x 10" M (15). The phytotoxin was characterized by spectrometric analyses and chemical conversion as (-)-dihydropyrenophorin (Vl), an important di lactone macrolide (15). However, the major product obtained in our extraction procedure used to isolate (-)-dihydropyrenophorin was the diol VII (j 6), which was not active in our bioassay tests. 

Bacteria overall > 410 Groom, 1992 Scarce diversification between land and sea. ALKAL. indole, phenazine, pyperazine, pyrrole, polypyrrole. PEPT. various classes, including siderophores. POLYKET. lactones, macrolides, quinones. CARBOH. (amino)glycoside, terpenoids hi hi ... 

The problem of macrolactonization became especially crucial in the 1960s as intensive studies were directed at the synthesis of biologically active antibiotics containing the macrocyclic lactone (macrolide) moiety. As a result of these studies,the problem of macrolactonization, regardless of the size of lactone ring or the complexity of the acyclic precursor, was solved. 

Chemical/Pharmaceutical/Other Class Avermectins are a group of chemically related natural and semisynthetic macrocyclic lactones (macrolide endectocides) produced from the fermentation products of Streptomyces avermitilis. The... 

The biosynthesis of erythromycin can be divided into two phases (Scheme 1). In the first constructive phase of the pathway a set of key enzymes, collectively known as the polyketide synthase (PKS), assembles the typical polyketide chain by sequential condensation of one unit of propionyl-CoA and six units of methylmalonyl-CoA 6. The initially formed chain is cyclised to give the first macrocychc lactone (macrolide) intermediate 6-deoxyerythronolide B 7 [6,7]. In the second phase 6-deoxyerythronohde B is elaborated by a series of tailoring enzymes which carry out regiospecific hydroxylations, glycosylations and a methylation (of an added sugar residue) to give finally erythromycin A. The core polyketide structure is generated by the PKS in phase one, but the later steps of phase two are essential to produce active antibiotics. 

Efomycins, elaiophylin, and niphimycins (e.g., efomycin G, 42) are a series of related dimeric for-lactone macrolides produced by strains of Streptomyces sp. and have attracted some attention due to their ability to... 

The following discussion will briefly outline two categories of macrolide (large ring system) antibiotics the lactone macrolides that include clinically useful erythromycins and several related compounds and the ansamacrolides, the most prominent members being the rifamcyins. 

Masamune has made use of this property for synthesis of medium ring lactones (macrolides), for example, zearalenone dimethyl ether ethylene ketal (5) from the hydroxy ester (4). On treatment with mercuric trifluoroacetate at 25°, (4) is converted within 5 min. into the lactone (5) in >90% yield (recrystalhzed). 

A highly convergent synthesis of rutamydn B, a 26-membered lactone macrolide antibiotic has been achieved by intramolecular macrocyclization through Suzuki coupling of a linear alkenyl boronate with a terminal alkenyl iodide as the key step in high yield as reported by White et al. (Scheme 3.68) [103]. 

---