Mycarose methyl glycosides

XVIII has now been excluded,42 since the methyl glycoside of the sugar reacts rather rapidly with one mole of periodate per mole furthermore, in contrast to the behavior of mycaminose (XXI), no moiety with one carbon atom less has been isolated from the products of periodate oxidation. Oxidation of mycarose with hypoiodite affords a crystalline lactone with the empirical formula C7H12O4 this observation eliminates the possibility of the keto structure XX. Thus, mycarose appears to be a 2,6-dideoxy-3-C -methylhexose (XIX). In the original compound, the isovaleryl group must be esterified to the alcohol function at C4, since the methyl glycoside isovalerate obtained from carbomycin is only attacked by periodate after alkaline hydrolysis. 

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 methyl-branch is introduced at the C-3 position of tautomer 11 of the keton 9 by an electrophilic.attack with active methione (S-methyl-5 -adenosyl methionine). Thus the 2,6-dideoxy-4-keto-3-C-methyl-D-ery//iro glycoside 12 results which after reduction furnishes, e.g., D-mycarose (cf. also Ref. [5]). 

The O-methyl group of L-cladinose (2) is also derived from L-methionine. The O-methylation step does not, however, take place at the level of the nucleotide-sugar, but it occurs when the substrate is erythromycin C, which contains L-mycarose and D-desosamine as glycosidic components9 (see Scheme la). The O-methylation of the L-mycarose moiety of erythromycin C by a partially purified enzyme from Streptomyces erythreus was described by Alpine and Corcoran.10,11 The reaction catalyzed is shown in Scheme la. 

Relomycin (Table 7) was found in culture broths of S. hygroscopicus (242) and shown to be 20-dihydrotylosin by chemical and microbial reductions (242,243). Macrocin (3 -0-demethyltylosin), was found as a minor factor in tylosin (244). It is the immediate biosynthetic precursor of tylosin and can be produced by a biosynthetically blocked mutant of S. fradiae (245—248). 6-Deoxy-2-0-methyl-D-allose [921-90-4/, a neutral sugar in macrocin, is a constituent of cardiac glycosides from Antiaris toxicaria and named javose (9, R = H, R/ = CH3) (249). 2 "-0-Demethylmacrocin (DOMM) obtained from another mutant of S. fradiae (246,250—252), is the penultimate precursor of tylosin (245—248). Other mutant strains of S. fradiae yield shunt metabolites of tylosin in which mycinose is altered (251,252). CP-56,064 [88378-53-4] is an analogue of tylosin in which mycarose is replaced by amicetose (5, R = H, R = OH) (253). 

The labelled mycarose isolated was converted into its methylthioglycoside. The mass spectrum of this glycoside had a molecular-ion peak (M ) and fragment-ion peaks (64a), (64b), and (64c) that all retained the C-3-methyl group. All of these peaks were accompanied by additional peaks that were three mass units higher. The composition of the fragment ions was confirmed by high-resolution mass spectrometry. 

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