Macrolide sugars

Methods to synthesize novel glycan-contammg molecules are desirable for a variety of applications. For example, new macrolide sugars may display attractive antibiotic properties, new polysaccharides may have unanticipated pharmaceutical or industrial uses, and modifications to naturally occurring glycoconjugates could allow for exploration of structure—function relationships. While synthetic chemistry represents one route to these molecules, carbohydrate synthesis is notoriously difficult and not always generalizable. An alternative to synthetic chemistry is... 

No nucleotide derivatives of the macrolide sugars or their hypothetical precursors have yet been found which would support the proposed scheme. Therefore, it is possible that some of the final transformations of the macrolide sugars occur at the level of the preformed macrolide glycosides. 

Macrolides containing only neutral sugars were obtained from a platenomycin-producing organism (217,218). Four demycarosyl derivatives of platenomycins were isolated from biosyntheticaHy blocked mutants of S. platensis, two of these possessed a methyl group rather than an aldehyde (219). A pair of novel compounds related to carbomycin were isolated in which one contained an unusual 10,ll-dihydro-12,13-diol moiety, the other a 14-hydroxy-epoxyenone moiety (220). 

Macrolides are a group of antibiotics, produced in nature by many actinomycetes strains, that are composed of a 12- to 16-membered lactone ring, to which one or more sugar substituents is attached. They target the peptidyl transferase center on the 50S ribosomal subunit and function primarily by interfering with movement of the nascent peptide away from the active site and into the exit tunnel. 

The macrolide antibiotics are characterized by possessing molecular structures that contain large (12-16-membered) lactone rings linked through glycosidic bonds with amino sugars. 

P2j Z = 2 D = 1.17 R = 0.080 for 3,888 intensities. This is aconfigu-rational analysis of the macrolide antibiotic 23672RP from Streptomyces chryeus. All three sugar residues are pyranoid the conformation of the a-ketose is CX, with Q = 56 pm, 0 = 9° that of the / -D-mycinose (6-deoxy-2,3-di-0-methyl-D-allose) is 4Clt with Q = 59 pm, 0 = 6° and that of the / -L-mycarose (2,6-dideoxy-3-C-methyl-L-riho-hexose) is 1C4, with Q = 53 pm, 0= 177°. The O-5-C-l-O-l-C glycosidic torsion-angles are —71, —87, —83°. The atomic coordinates reported in the paper refer to the opposite enantiomer. 

The hydroxy groups in natural products like, for example, the macrolide antibiotics erythromycin, 1"1 and desmycosin, 2001 2011 as well as the 3-(hydroxymethyl)-2- or 3-cephems 2021 and derivatives of the amino sugar garamin 2031 have been converted into the carbamate function with CDI and amines. In the case of aminoglycoside antibiotics of the sisomicin series, thiocarbamates or dithiocarbamates have been prepared from alcohols or thiols using ImCSIm and amines.12041... 

Erythromycin is a macrolide antibiotic consisting of the aglycone, erythronolide A the aminosugar, desosamine and the neutral sugar, cladinose. 

Another basic drug where minor structural modification results in a dramatic increase in volume of distribution is the macrolide antibiotic, azithromycin. The traditional agent in this class is erythromycin, which contains one basic nitrogen, in the sugar side-chain. 

Inverse type hetero-Diels-Alder reactions between p-acyloxy-a-phenylthio substituted a, p-unsaturated cabonyl compounds as 1-oxa-1,3-dienes, enol ethers, a-alkoxy acrylates, and styrenes, respectively, as hetero-dienophiles result in an efficient one step synthesis of highly functionalized 3,4-dihydro-2H-pyrans (hex-4-enopyranosides). These compounds are diastereospecifically transformed into deoxy and amino-deoxy sugars such as the antibiotic ramulosin, in pyridines having a variety of electron donating substituents, in the important 3-deoxy-2-gly-culosonates, in precursors for macrolide synthesis, and in C.-aryl-glucopyranosides. 

The macrolide antibiotics are those that consist of a large lactone ring to which sugars are attached. Antibiotics in this group include erythromycin (Ilotycin, E-mycin,... 

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