Mycinose

A few neutral 16-membered macroHdes have been isolated. The stmcture of chalcomycin (54, R = CH3, R = OH), produced by S. bikiniensis was estabhshed as a 16-membered lactone having two neutral sugars, D-chalcose (7) and D-mycinose (9, R = R = OH3) (293—295). Its aglycone resembles that... 

This tool has been of great value in the elucidation of the structures of some important biologically-derived amino (14) and deoxy (13) sugars in the form of their dialkyl dithioacetals. Tedious degradation reactions which would require both time and valuable material could be avoided in many cases by resorting to mass spectrometry. The antibiotic sugars (22) paramose (1), mycinose (2) and chalcose (3) were, for example, studied by mass spectrometry (13, 14). 

Scheme 10.10 Final steps in mycinamicin biosynthesis. Des desosamine Myc mycinose. 

Mycarose Mycinose Neuraminic acid (Neu) 2,6-D ideoxy-3- C-methy I-l- ribo- hexose 6-Deoxy-2,3-di-Omethyl-D-allose 5-Amino-3,5-dideoxy-D-g/ycero-D-ga/acfo-non-2-ulosonic acid... 

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. 

This interesting transformation from a readily available 6-deoxyhexose forms the basis for the synthesis231 of 6-deoxy-2,3-di-0-methyl-D-allose (mycinose),168 one of the carbohydrate moieties of the antibiotic chalco-mycin. The synthesis merely involves the protection of the C-5 hydroxyl group in (41) by benzylation, followed by partial hydrolysis with acid, methylation of the product at the C-2 and C-3 hydroxyl groups, and debenzylation. 

Selective Cleavage of the Mycinose Sugar from the Macrolide Antibiotic Tylosin... 

Desosamine (154), in which the 3-O-methyl group of chalcose is replaced by a dimethylamino group, is found in the macrolide mycinamicin I (158).230,233 Genes for the synthesis of the two deoxy sugars of chalcomycin, D-chalcose, and D-mycinose were characterized in a gene cluster from S. bikiniensis.230... 

When tylosin binds to the ribosome, the mycinose extension from C14 of the lactone ring extends down the exit tunnel and interacts with domain II of rRNA (Fig. 4.8 B). Nucleotide modification by N1 methylation of Ec G748 (Hm A841) in... 

Removal of both neutral sugars from tylosin yields 5-O-mycaminosylty-lonolide (OMT) (19) Figure 5.9) however, the conditions necessary to hydrolyze the relatively stable sugar mycinose require careful control... 

Oxidation of the hydroxyl group of mycinose yielded an unstable ketone, thereby providing methods for cleaving this sugar [140, 141] however, the parent demycinosyltylosin is more efficiently obtained from mutant strains of S. fradiae [74]. A mild procedure for reductive amination of this unstable ketone with TiCl3 and NaBHjCN has been developed [142]. Conversion of mycinose in some C-20-modified derivatives into a 3",4"-unsaturated sugar introduced some in vitro antifungal activity into the traditional antibacterial spectrum [143]. 

Matsumoto, T, Maeta, H, Suzuki, K, Tsuchihashi, G, New glycosidation reaction 1. Combinational use of Cp2ZrCl2-AgC104 for activation of glycosyl fluorides and application to highly 3-selective glycosidation of D-mycinose, Tetrahedron Lett., 29, 3567-3570, 1988. 

Nicolaou and co-workers successfully prepared a tylonide derivative with the mycinose sugar attached to the proper position on the lactone ring (Scheme... 

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