Narbomycin macrolides

Compound 17 is the so-called (+)-Prelog-Djerassi lactonic acid derived via the degradation of either methymycin or narbomycin. This compound embodies important architectural features common to a series of macrolide antibiotics and has served as a focal point for the development of a variety of new stereoselective syntheses. Another preparation of compound 17 is shown in Scheme 3-7.11 Starting from 8, by treating the boron enolate with an aldehyde, 20 can be synthesized via an asymmetric aldol reaction with the expected stereochemistry at C-2 and C-2. Treating the lithium enolate of 8 with an electrophile affords 19 with the expected stereochemistry at C-5. Note that the stereochemistries in the aldol reaction and in a-alkylation are opposite each other. The combination of 19 and 20 gives the final product 17. 

As a model study for this methodology, Evans and Bartroli carried out the synthesis of (+)-Prelog-Djerassi Lactonic acid 47 [14b] [27], which is a degradation product of either methymycin or narbomycin [28] and has some of the important structural features present in macrolide antibiotics. 

Pike, the P-450 hydroxylase in the pikromycin gene cluster catalyzes hydroxylation of the initial macrolide products (YC-17/narbomycin) and displays unparalleled flexibility toward the macrolactone core of its macrolide substrates. Both 12-membered ring YC-17 (4) and 14-membered ring narbomycin (5) are produced after glycosylation with desosamine. Interestingly, PikC catalyzes hydroxylation at CIO or C12 of the... 

Allen reported in 1977 that naturally occurring 3-oxo (or 3-keto) macrolides such as pikromycin (81a) and narbomycin (81b) (Fig. 19) do not induce mac-rolide resistance in S. aureus, and they retained sufficient antibacterial activity [108]. On the other hand, derivatives of 3-decladinosyl-3-oxo-6-0-methyl EM (82) (Fig. 20) have been recently synthesized and designated as ketolides [109]. They generally exhibit significant activity against EM-resistant Gram-positive pathogens, and the features of their activity are fairly different from those of EM derivatives that bear cladinose at the C-3 position. 

Structures of Narbomycin and Related Macrolide Antibiotics and obtained the D.Sc. (habilitation) degree. That same year he moved to the newly formed Institute of Organic Chemistry of the Polish Academy of Sciences (IOC) in Warsaw, first as a Docent (Associate Professor) and from 1973 as a full Professor until the year of his retirement. In 1968, he succeeded Professor Osman Achmatowicz as head of the Department of Synthesis of Natural Products. After reorganization of the Institute and the departure of the alkaloid laboratory to Poznan, he became head of the laboratory responsible for the synthesis of mono- and oligo-saccharides. Between 1979 and 1982 he served as the Research Director of the Institute. After retirement at the age of seventy, he continued his association with the Institute as Professor Emeritus. 

Betlach, M.C. et al.. Characterization of the macrolide P-450 hydroxylase from Streptomyces vene-zuelae which converts narbomycin to picromycin. Biochemistry, 37, 14937, 1998. 

The Prelog-Djerassi lactone is a degradation product of the macrolide antibiotics methy my cin and narbomycin. Evans uses it here to illustrate his asymmetric enolate methodology (see section 5.3.2). Of the many syntheses of tnis popular target molecule, this is one of the best in terms of diastereo- and enantioselectivity. 

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