Starting materials from metabolites

Microbial transformations of ellipticine (15) and 9-methoxyellipticine (16) were reported by Chien and Rosazza (143, 144). Of 211 cultures screened for their abilities to transform 9-methoxyellipticine (16), several, including Botrytis alii (NRRL 2502), Cunninghamella echinulata (NRRL 1386), C. echinulata (NRRL 3655), and Penicillium brevi-compactum (ATCC 10418), achieved O-demethylation of 16 in good yield (Scheme 9). P. brevi-compactum was used to prepare 9-hydroxyellipticine (22) from the methoxylated precursor, and 150 mg of product was obtained from 400 mg of starting material (37% yield). The structure of the metabolite was confirmed by direct comparison with authentic 9-hydroxyellipticine (143). O-Demethylation is a common microbial metabolic transformation with 16 and many other alkaloids (143). Meunier et al. have also demonstrated that peroxidases catalyze the O-demethylation reaction with 9-methoxyellipticine (145). 

Cycloaddition to endocyclic unsaturation has been used by many researchers for the preparation of isoxazoUdinyl adducts with y-lactams derived from pyrogluta-minol and is discussed later in this chapter as a synthesis of unusual amino acids (Scheme 1.20, Section 1.6) (79,80). A related a,p-unsaturated lactam has been prepared by a nitrone cycloaddition route in the total synthesis of the fungal metabolite leptosphaerin (81). A report of lactam synthesis from acyclic starting materials is given in the work of Chiacchio et al. (82) who prepared isoxazolidine (47) via an intramolecular nitrone cycloaddition reaction (Scheme 1.11). 

Vertebrates cannot convert fatty acids, or the acetate derived from them, to carbohydrates. Conversion of phosphoenolpyruvate to pyruvate (p. 532) and of pyruvate to acetyl-CoA (Fig. 16-2) are so exergonic as to be essentially irreversible. If a cell cannot convert acetate into phosphoenolpyruvate, acetate cannot serve as the starting material for the gluconeogenic pathway, which leads from phosphoenolpyruvate to glucose (see Fig. 15-15). Without this capacity, then, a cell or organism is unable to convert fuels or metabolites that are degraded to acetate (fatty acids and certain amino acids) into carbohydrates. 

In a major study of the microbial metabolism of acronycine (177), Rosazza and co-workers examined 47 cultures for their capacity to transform this alkaloid, 10 of which were active in producing metabolites more polar than the starting material. The major metabolite was identified as the 9-hydroxy derivative 177 following isolation from the incubation of 176 with Cunninghamella echinulata NRRL 3655. This product was characterized as the acetate 182 by MS and PMR analysis, the latter technique... 

Dichloro-3,6-diisobutylpyrazine (237) is the starting material for a very similar synthesis of pulcherriminic acid (10).430 Pulcherri-minic acid, as already mentioned in Section I, is derived from pulcherrimin (9), a metabolite of the yeast Candida javlcherrima. The key step in the synthesis of pulcherriminic acid is the initial step of... 

The positive and negative ion mass spectra of metabolite 5. are shown in Figure 6. The starting material in this experiment was labeled only with 14C in the pyridine ring so that any ions associated with a metabolite will display a M+2 doublet. The highest-mass ion in the positive ion spectrum is found at m/z 532 and arises via loss of glutamic acid from the protonated molecular ion. This... 

---