Nucleoside antibiotics synthesis

Nucleoside antibiotics biosynthesis, 1, 88-90 Nucleosides oxa analogues, 3, 1085 as pharmaceuticals, 1, 153 protected, 5, 316 Nucleosidin occurrence, 5, 603 Nupharolutine synthesis, 2, 393 Nybomycin applications, 6, 667 Nybomycin, deoxy-applications, 6, 667 Nystatin antifungal agent veterinary use, 1, 211... 

The furanoid vinyl ethers described above are of interest in view of the structure of the nucleoside antibiotic angustmycin A (2) (15) which also contains an exocyclic double bond. As a first step towards the synthesis of analogs of angustmycin A (2), preparation of exocyclic vinyl ethers from hexulofuranoid derivatives was studied. Benzoylation of 2,3 4,6-di-0-isopropylidene-a-L-ryZo-hexulofuranose (44) followed by selective acid hydrolysis of the 4,6-O-isopropylidene group afforded l-0-benzoyl-2,3-0-isopropylidene-a-L-ryZohexulofuranose (45) in 72%... 

The number of naturally occurring, organic fluorine compounds is very small indeed. Compound 1 is1 a nucleoside antibiotic that contains fluorine attached to the carbohydrate ring, replacing H-4 in the D-ribosyl moiety. The presence of fluorine was shown by -n.m.r.-, 19F-n.m.r.-, and mass-spectral data, and the structure of this compound has been confirmed by independent synthesis.9,10... 

Nucleocidin (LXXX) [353], an adenine nucleoside antibiotic whose structure has recently been elucidated, is also a potent inhibitor of protein synthesis. Studies with this compouna have led to the conclusion that nucleocidin forms a complex with ribosomes which is inactive in peptide bond formation. Binding... 

Diazopyrazoles and imidazoles are useful intermediates in the synthesis of pyrazolo- and imidazolo-tetrazinones, which have shown anticancer activity, especially the mitozolomide that had curative activity against L1210 and P388 leukemia (84JMC1% 87JMC357). 4-Diazopyrazole are used in the synthesis of C-nucleoside antibiotics such as pyrazolomycin [81JCS(P1)2374]. 

Isolation and characterization of the nucleoside antibiotic formaycin as 3-j8-ribofuranosylpyrazolo[4,3-[Pg.346]

Amino sugars are components of antibiotic substances109 and bacterial polysaccharides,1,0 and are therefore of interest. The nucleoside antibiotics amicetin, bamicetin, and plicacetin contain, as the sugar residue, a monoaminopentadeoxy disaccharide that is closely related to maltose. In view of the reported antibiotic and antitumor properties of these pyrimidine nucleosides,111,112 the synthesis of aminodeoxy derivatives of maltose would be of interest. 

This alkylation strategy has been successfully implemented to the diastereoselective synthesis of a number of biologically active compounds,17 19 32 72 73 including the orally active HIV protease inhibitor Crixivan (>95% de)17-19 and nucleoside antibiotic (+)-sinefungin (51) (>99% de).72 The C-6 amine stereochemistry of (+)-sinefungin was set by a highly diastereoselective allylation of (lS,2/ )-l-amino-2-indanol-derived oxazolidinone 52 (Scheme 24.10). 

Synthesis of oxetanocine, a nucleoside antibiotic with anti-HIV action, and of related compounds 91YGK670. 

Seleno esters are also produced in good yield by reactions of dimethy-laluminim methanoselenolate103 (CH3)2AlSeCH3, with the protected C-ribofuranosyl acetate 269. Treating the selenol ester 270 with either cuprous or mercuric chloride produced the (Gensler) lactone.110 271, a product useful in the synthesis of various C-nucleoside antibiotics.111,112... 

The liposidomycins are a family of novel lipid-containing nucleoside antibiotics which inhibit bacterial peptidoglycan synthesis. A crucial component of their stmctures is a substituted l,4-diazepan-3-one moiety. As part of work to assign stereochemistry in these antibiotics, analogues of this moiety have been synthesised using a reductive amination/ring cyclisation approach <03H(59)107>. The compounds synthesised were 57 and 58. 

The 4,5-unsaturated pyranoses or 3,4-unsaturated furanoses are usually prepared by a base-catalyzed elimination of a leaving group such as halogen, sulfonyloxy etc. from appropriate sugar derivatives. The classical example is represented by the synthesis of compound 19 from l,2 5,6-di-0-isopropylidene-a-D-glucofuranose 18 [1]. Analogous elimination performed for 20 led to derivative 21 from which capuramycin—a complex nucleoside antibiotic could be prepared readily (O Scheme 14) [30]. 

The first total synthesis of the nucleoside antibiotic herbicidin B was accomplished in the laboratory of A. Matsuda. The key step was a novel aldol-type C-glycosidation reaction promoted by Sml2 between a 1-phenylthio-2-ulose derivative and a 1- 3-D-xylosyladenine-5 -aldehyde derivative. During the preparation of the phenylthio sugar subunit, the Moffatt oxidation was applied to convert the primary alcohol to the corresponding aldehyde, which was immediately oxidized with PDC in DMF/MeOH to the methyl ester. The reaction conditions were completely compatible with the silyl protecting group as well as the thioacetal functionality. 

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