Showdomycin, synthesis

These acid-catalyzed C-glycosylations were successfully extended to the D-ribofuranose series by Sorm and coworkers,148 who utilized the reaction in the first reported synthesis of showdomycin. Thus, treatment of 2,3,5-tri-0-benzoyl-/3-D-ribofuranosyl bromide (81) with 1,2,5-trimethoxybenzene in the presence of zinc oxide gave 2,4,6-trimethoxy-l-(2,3,5-tri-0-benzoyl-/3-D-ribofuranosyl)benzene (196). Ozonolysis of the corresponding acetate derivative, followed by esterification, gave the highly functionalized C-/3-I>ribofuranosyl derivative (197), which was used as a key intermediate in the synthesis of showdomycin (see Section III,l,b). 

Showdomycin inhibits synthesis of nucleic acid. Thiols, such as cysteine and glutathione (among other compounds), reverse this inhibition, and it is considered that the interaction of the maleimide moiety with sulfhydryl groups within the cell or in the membrane may be responsible for the selective inhibition of enzymes by show-... 

The synthesis of the antibiotic showdomycin, starting from a ribose derivative, is illus-trative." ... 

Enzymic discriminations of enantiopic groups of weso-compounds have been widely exploited in asymmetric synthesis. Ohno and co-workers reported a total synthesis of L- and D-ribose, showdomycin and cordycepin based on the optically active half-esters 56 and 57, which were obtained enzymatically (Pig Liver Esterase PLE) from the corresponding mcso-diesters 54 and 55, respectively, derived from the Diels-Alder adduct 53 of furan to dimethyl acetylenedicar-boxylate. The diesters 58 - 60 were also found to be good substrates for PLE leading to the corresponding half-esters 61 - 63 with high enantiomeric purities. ... 

While numerous applications of anomeric radicals exist, three examples serve to illustrate possible future applications and directions for this chemistry. Barton has developed a short and convergent synthesis of the C-nucleoside showdomycin 292 (Scheme 80) [127]. Kessler has prepared an interesting C-linked glycopeptide unit 294 via radical addition to a dehydroaminoacid acceptor 293 (Scheme 81) [137]. In the latter example, good anomeric stereo-... 

Racemic analogs of showdomycin have been synthesized from adducts (352 and 353) of methyl 2-nitroacrylate with furan. Synthesis of DL-2-ept-showdomycin involved treatment of the adducts with m-chloroperoxybenzoic acid, followed by nitrous acid elimination, to give the alkenic epoxide 379. Opening of the oxirane ring, and a sub-... 

Y. Araki, T. Endo, M. Tanji, J. Nagasawa, and Y. Ishido, Additions of a ribofuranosyl radical to olefins. A formal synthesis of showdomycin. Tetrahedron Lett. 29 351 (1988). 

NCIMB 9872, overexpressed in E. coli, as a whole cell biotransformation [167], The substrate, an oxabicycloketone, was successfully converted to the corresponding heterobicyclic lactone (Fig. 28) in 70% yield with an enantiomeric excess of 95%. This access to the chiral intermediate for several naturally occurring compounds, including (+)-frans-kumausyne and (+)-showdomycin, represents the first application of a whole cell biotransformation using recombinant E. coli with CPMO in natural product synthesis. 

The adducts resulting from Diels-Alder reaction of pyridyl sulfoxides with furan have been used in the synthesis of a number of natural products. Thus, a new procedure for the total synthesis of optically actives C-nucleosides was reported by Koizumi et al. [38], who prepared D-showdomycin (19) and (D)-3,4-0-isopropylidene-2,5-anhidroallose (20) from the endo(t) 18a adduct (Scheme 10). (-i-)-Methyl 5-epishikimate (21) [39] and pentaacetyl- -D-mannopyranose (22) [40] were also obtained starting from endo(t) 18a (Scheme 10), the cleavage of the oxygenated bridge being the key step of these transformations. 

C02Me, etc.) were formed in good yield. A short and high-yielding synthesis of showdomycin 133 (Scheme 34) illustrated the utility of the method.88 D-Ribose was converted to the known derivative 134 which, on mesylation and displacement with anisyltelluride anion, gave 135. Methyl radical exchange on 135 in the presence of maleimide gave 136 which, on oxidation to sulfoxide and elimination, afforded the derivative 137. Standard deprotection procedures readily transformed 137 into the antibiotic showdomycin 133. The overall yield was about 30%. 

C-Nucleosides. The first step in a new synthesis of C-nucleosides involves reaction of ethoxycarbonylethylidenetriphenylphosphoranc with the 2,3-di-O-isopropylidene-D-ri-bose derivative 1 to give the acyclic product 2. On treatment with C6H5SeCl, 2 gives a single cyclic ribose derivative (3), shown to be the 3-anomer by the conversion shown here to a derivative (6) of showdomycin. In addition, several other 1 p-substituted 1-deoxyribose derivatives were prepared. 

Phenylselenoetherification. This reaction provides a short synthesis of the C-nucleosides showdomycin (10) and epishowdomycin (11) from D-ribosc (7). Thus the stabilized ylide 8, derived from maleimide, couples with 7 in acetic acid to form 9. Cyclization with QH SeCl in refluxing trimethyl borate gives an unstable product, which on oxidation gives a mixture of 10 and 11. 

This methodology has been used to provide efficient protocols for the asymmetric allylic alkylation of p-keto esters, ketone enolates, barbituric acid derivatives, and nitroalkanes. Several natural products and analogs have been accessed using asymmetric desymmetrization of substrates with carbon nucleophiles. The palladium-catalyzed reaction of a dibenzoate with a sulfonylsuccinimide gave an advanced intermediate in the synthesis of L-showdomycin (eq 3). ... 

Ohno, M., Ito, Y, Arita, M., Shibata, T., Adachi, K., and Sawai, H., Synthetic studies on biologically active natural products by a chemicoenzymatic approach. Enantioselective synthesis of C- and N-nucleosides, showdomycin, 6-azapseudouridine and cordycepin. Tetrahedron, 40, 145, 1984. 

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