Erythromycin chemistry

MOTILIN AGONISTS MACROLIDES AND ERYTHROMYCIN CHEMISTRY, PHARMACOLOGICAL EFFECTS, AND MECHANISM OF ACTION... 

Gokhale, R.S., Hunziker, D., Cane, D.E. and Khosla, C. (1999) Mechanism and specificity of the terminal thioesterase domain from the erythromycin polyketide synthase. Chemistry Biology, 6, 117. 

Anandatheerthavarada, H.K. etal. (1999) Physiological role of the N-terminal processed P4501A1 targeted to mitochondria in erythromycin metabolism and reversal of erythromycin-mediated inhibition of mitochondrial protein synthesis./oumoi of Biological Chemistry, 274 (10), 6617-6625. 

In his 1956 article in Perspectives in Organic Chemistry , the late Professor R. B. Woodward characterized the macrolide antibiotic erythromycin as a synthetic challenge which is ... quite hopelessly complex, especially in view of its plethora of asymmetric centers 70). Twenty-five years after making this dismal prognosis,... 

Chemistry of the glycoside linkage. Exceptionally fast and efficient formation of glycosides by remote activation, Carbohydr. Res. 80 07 (1980). (e) K. Wiesner, T. Y. R. Tsai, and H. Jiu, On cardioactive steroids. XVI. Stereoselective P-glycosylation of digitoxose the synthesis of digitoxin, Helv. Chim. Acta 60 300 (1985). (f) R. B. Woodward (and 48 collaborators), Asymmetric total synthesis of erythromycin. 3. Total synthesis of erythromycin, J. Am Chem. Soc. 103 3215 (1981). (g) P. G. M. Wuts and S. S. Bigelow, Total synthesis of oleandrose and the avermecin disaccharide, benzyl ot-L-oleandrosyl-ot-L-4-acetOxyoleandroside, J. Org. Chem. 43 3489 (1983). 

Staunton J and Wilkinson B (1999) Biosynthesis of erythromycin and related macrolides. Comprehensive Natural Products Chemistry, Vol 1. Elsevier, Amsterdam, pp 495-532. 

Macrolide antibiotics, in some instances, may be considered as hydroxy acid derivatives. In addition, many of them have carbohydrates attached, often with unique structural features, as illustrated by erythromycin (20).53 Although some of these antibiotics are semi-synthetic, all are derived by a fermentation process where the antibiotic is formed as a secondary metabolite. This approach, of course, alleviates the need to perform complex carbohydrate chemistry (see Chapter 19). 

S. Hanessian, C. Bacquet, and N. Lehong, Chemistry of the glycosidic linkage, exceptionally fast and efficient formation of glycosides by remote activation, Cabohydr. Res. S0 C17 (1980). R. B. Woodward, et al. Asymmetric total synthesis of erythromycin. 3. Total synthesis of erythromycin, J. Am. Chem. Soc. 103 3215 (1981). 

The C10-C13 segment 24 was prepared from D-ribose (35) (O Scheme 2). In this case, selective protection of the hydroxy groups was realized by isopropylidenation (from 35 to 36). One of the other procedures for conversion of cyclic monosaccharides to acyclic derivatives is nucleophilic addition to the anomeric position in free monosaccharides. Grignard reagent, MeMgl, was added to 36 to provide 37 as the sole product. The subsequent manipulation of 37 to the C10-C13 segment 24, which is not restricted in monosaccharides chemistry, is summarized in O Scheme 2. After the completion of the synthesis of erythronolide A (20), Toshima, Nakata, Tatsuta, Kinoshita, and coworkers achieved the total synthesis of erythromycin A (18) by their own glycosidation method [18,19]. 

The first research project that Alex undertook in the Institute was directed to the chemistry of the macrolide anitibiotic, erythromycin. Chemical modifications led to a new derivative, 8-hydroxyerythromycin, a patent on which was purchased by a major pharmaceutical company. At the same time, Alex initiated studies on the total synthesis of monosaccharides via the Diels-Alder adduct of... 

CHEMISTRY OF ERYTHROMYCIN Structure and physical-chemical data Total synthesis Intramolecular cyclization... 

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. 

Further routes to segments of aglycones of the erythromycin group have appeared. The laevoglucosan-derlved epoxytosylate (36) was converted into C(l)- C(5) and C(9)- C(15) fragments (37) and (38) of 6 deoxyerythronolide B, as outlined in Scheme 9 similar chemistry was also used to prepare the C(9)- C(15) fragment (39)... 

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