Erythromycin partial synthesis

In a remarkable experiment (scheme 5) S. F prepared diglycosidated seco acid 17 from 2 Martin and M. Yamashita [13] have parted via partial synthesis in ten steps and subjected with the accepted philosophy of erythromycin it to Yamaguchi s macrolactonization conditi-synthesis, namely to perform first the lactoni- ons. However, this protocol afforded only zation and then the glycosidation. They minor amounts of the desired macrolide 18,... 

The chemistry of natural products encompasses their isolation, structure elucidation, partial and total synthesis, elucidation of their biogenesis, and the biomi-metic synthesis of N. p. Major breakthroughs in analysis were, e.g., the structural clarifications of morphine, lignin, insulin, estrones, and cholesterol as well as the elucidation of the biosyntheses of terpenoids, morphine, penicillin, chlorophyll, and vitamin B 2. Major advances in synthetic chemistry were, e.g., the total syntheses of camphor, hemin, quinine, saccharose, tropine, stryehnine, chlorophyll, vitamin B 2, erythromycin, taxol and palytoxin. Numerous N. p. of the so-ealled ehiral pool are used as starting materials for the synthesis of optically active compounds or serve (in the form of their derivatives) as catalysts for enantioselective syntheses. 

Several gene dusters encoding the enzymes of polyketide synthesis have been cloned (partially or completely). Aromatic polyketides (e.g., tetracyclines, actinorho-dine, and anthracyclines) are synthesized by type II PKSs, which are multienzyme OMn-plexes similar to FAS type II (63). In contrast, the polyketide chain of mactolide antibiotics such as erythromycin and avermectin are synthesized by PKS type I, consisting of large multifunctional polypeptides similar to FAS type I but composed of repeated units or "modules" with each active site carrying out only one reaction in the assembly and modification of each carbon chain (64,65). 

Several rare amino sugars have been found in antibiotics. From puro-mycin (Achromycin), 3-amino-3-deoxy-D-ribose has been isolated by Waller and co-workers 260). The configuration of the amino sugar was confirmed by its synthesis from L-arabinose, with methyl 2,3-anhydro-i -L-ribopy-ranoside 261) as an intermediate (p. 392). Among the hydrolysis products of erythromycin, obtained from Streptomyces erythreus, is an amino sugar with the empirical formula CsHnNOs. Its structure has been partially determined as a 3-dimethylamino-3,4,6-trideoxyhexose 262). On hydrolysis... 

Some bacteria are resistant to penicillin, because they produce an enzyme, penicillinase, that destroys the /3-lactam ring in the antibiotic. Synthesis of analogs afforded a partial solution to this problem. Ultimately, however, it became necessary to turn to antibiotics with completely different modes of action. Erythromycin, produced by a strain of Streptomyces bacteria first found in soil samples in the Philippines in 1952, functions in a distinct manner. It is a large ring lactone that interferes with the bacterial ribosome, its cell-wall protein S5mthesis factory. Although erythromycin is unaffected by penicillinase, bacteria resistant to it have developed over the decades since its introduction into the antibiotic arsenal. 

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