A new chiral synthesis of (–)-anisomycin and its demethoxy analogue

Abstract

Anisomycin (1 a) and its demethoxy-analogue (1 b) have been prepared enantiospecifically and stereoselectively from D-ribose.

Synthesis of the indole nucleoside antibiotics neosidomycin and SF-2140

“…The resultant black oil was dissolved in diethyl ether and added to ethereal diazomethane. After 1 h, the excess of diazomethane was destroyed with glacial acetic acid and the residue, obtained after evaporation, was chromatographed on silica gel, with light petroleumdiethyl ether (1 : 1) as eluent, to give the uronic ester 12 (4.8 g, 72%) as an oil, [a]D +40.4 (c 0.96, MeOH); 6,(360 MHz) 1.30 and 1.45 (each 3 H, s, CMe,), 2.1 1 13.9, J4eq,3 -J4eq,5 -5, 4-Heq), 3 (1 H, dt, Jgem 14.0, J4ax,3 -J4ax,5 -7, 4-Ha"), 2.29 (1 H, dt, Jsem 14.-A stirred solution of the uronic ester 12 (1.97 g) in glacial acetic acid (45.7 cm3)-acetic anhydride (15 cm3) was cooled to OOC, phereupon glacial acetic acid (4.6 cm3) and conc. sulfuric acid (0.44 cm3) were added in one batch.…”

“…The residue obtained after evaporation was chromatographed twice on silica, with light petroleumdiethyl ether (6:5) as eluent. The residue obtained on evaporation of product-containing fractions was subjected to preparative TLC [developer : light petroleum-diethyl ether (3 (6) To a stirred solution of 3-(cyanomethyl)indole 20 (0.234 g) in dry acetonitrile (3 cm3) was added sodium hydride (50% dispersion in mineral oil; 0.076 g) at room temperature under nitrogen. The mixture was stirred for 30 min and was then cooled to 0 "C. A solution of the glycosyl chloride 33 (0.6 g) in dry acetonitrile (3 cm3) was added dropwise to the reaction mixture, which was maintained at 0 "C for 24 h. The solution was filtered and the filtrate was evaporated to give a brown oil, which was chromatographed on silica, with light petroleumdiethyl ether (2: 1) as eluent, to give the UV-active product (0.32 g, 44%) as an amorphous foam.…”

“…Traces of an isomeric impurity were removed by crystallisation from diethyl ether-light petroleum to give nucleoside 35 (0.24 g, 31%), m.p. 170 "C; [a],, +20.9 (c 0.95, CHCl,); 6,(360 MHz) 0.82 and 1.24 (each 9 H, s, OF%), 3 After 6 days, Amberlite resin (IRC 50, H+-form) was added and the mixture was stirred for 1 h prior to filtration. The filtrate was added to ethereal diazomethane and the solution was kept for 1 h. The excess of diazomethane was destroyed with glacial acetic acid and the solution was evaporated to give a semi-solid mass, which was chromatographed on silica, with light petroleumethyl acetate (1 : 1) as eluent, to give SF-2140 3 (0.097 g, 76%) as a glass;dH[200 MHz; (CD,),CO] 2.28 (1 H, ddd, J 14.3, J4rax,5, 7.0, s, C02Me), 3.90 (…”

“…This compound, termed SF-2 140, was subjected to degradative, spectroscopic and X-ray crystallographic studies, as a result of which the structure 3 was determined for SF-2140, in which the 4-deoxyhexuronic acid unit has the D-fyxo-configuration. Since, however, the 'H NMR data for compound 3 and its di-0-acetyl derivative 4 showed, in particular, large coupling constants J , p , 2 3 and J4,ar,5,r it was suggested that, in solution, compounds 3 and 4 adopt twist-boat conformations ('S,) as indicated by structure 4' in the case of the di-0-acetyl derivative. Interestingly, in the crystal structure, the methyl uronate ring of compound 3 adopts a ' C4 (D) conformation.…”

New Developments in the Synthesis of Anisomycin and Its Analogues

“…D-Ribose was used for the synthesis of (-)-anisomycin (1) and its phenylanalogue 34 (Scheme 3) [55,56]. Thus, 2,3-O-isopropylidene-D-ribose (17) [57] was treated with Grignard reagents, benzyl-and p-methoxybenzyl-magnesium bromide to give the corresponding triols 18 (77%) and 19 (70%); only the D-allo stereoisomer could be isolated in each case.…”