Synthesis of bromodeoxy sugars from hexoses, alditols, and aldonic acids

Abstract

-Reaction of hexoses, anhydroalditols, and aldonic acids with hydrogen bromide in acetic acid leads to the formation of acetylated bromodeoxy compounds. The reaction proceeds by partial acetylation and formation of acetoxonium ions followed by substitution with bromide. Hexases react only in the furanose form to give 6-bromo compounds. Most 1,4-and 1,5-anhydrides of hexitols give mono-or dibromides. Aldonic acids, or their lactones, yield mono-or dibromolactones with bromine at C-2 and at the primary carbon atom. Same aspects of the chemistry of the bromolactones are discussed.

Development of a Novel Synthetic Process for 2-Deoxy-3,5-di-O-p-toluoyl-α-l-ribofuranosyl Chloride: A Versatile Intermediate in the Synthesis of 2‘-Deoxy-l-ribonucleosides

“…The reaction time was greatly reduced under these conditions (see Experimental Section for detail). Such short reaction time is a significant improvement of the process over the existing literature protocols , that require days to prepare the dibromolactones. The crude product of our new process was triturated with 20% n -heptane in isopropyl ether to get pure 2,5-dibromo-2,5-dideoxy- d -lyxono-1,4- lactone ( 5 ) as light brown crystals.…”

“…The C-2 debromination of 5 using iodide ion was examined in detail. This reaction was found to be sluggish when conducted at room temperature using potassium or sodium iodide and trifluoroacetic acid (TFA) in acetone, 18a-c 2-butanone, or isopropyl acetate (IPAc). When heated at reflux, the reaction was considerably faster and required fewer equivalents of the iodide ion to go to completion.…”

“…The lactone 7 thus formed would be opened by aqueous alkali to the aldonic acid salt 11 , which however, would regenerate the lactone 7 upon acidification. The stereochemical assignment of lactone 7 was based primarily on the work of Bock et al18a where 7 was synthesized from d -lyxono-1,4-lactone via a similar sequence of reactions. The stereochemistry at C-3 and C-4 of d -xylono-1,4-lactone ( 4 ) being respectively identical to that at C-3 and C-4 of d -lyxono-1,4-lactone, the above stereochemical assignment of lactone 7 is unequivocal.…”

“…Before taking to complete dryness, n -heptane (200 mL) was added to the thick oil and it was evaporated in vacuo at 50 °C to give a brown semisolid. A solution of 100 mL of n -heptane in 400 mL of isopropyl ether was added to it, and the mixture was stirred at room temperature for 4 h. Filtration of the slurry and vacuum-drying of the cake at 30−35 °C overnight yielded pure 2,5-dibromo-2,5-dideoxy- d -lyxono-1,4-lactone ( 5 ) as a light brown solid (71.9 g, yield 40% over 2 steps); mp 90−93°C; lit 18b. mp 92−93°C; 1 H NMR (DMSO- d 6 , 400 MHz) δ 6.37 (1H, d, J 6.1 Hz, exchangeable with D 2 O, 3-O H ), 5.32 (1H, d, J 4.6 Hz, H-2), 4.77−4.7 (1H, m, H-4), 4.43−4.37 (1H, m, H-3), 3.76−3.6 (2H, d of an AB q, Δυ = 36.6 Hz, J 10.5, 8.1, and 5.6 Hz, 2 × H-5); 1 H NMR (CDCl 3 , 400 MHz) δ 4.8 (1H, d, J 4.4 Hz, H-2), 4.73−4.66 (1H, m, H-4), 4.66−4.61 (1H, m, H-3), 3.77−3.63 (2H, m, 2 × H-5), 2.66−2.61 (1H, br s, 3-O H ); 13 C NMR (DMSO- d 6 , 100 MHz) δ 171.3, 81.6, 69.2, 48.9, 29.2; 13 C NMR (CDCl 3 , 100 MHz) δ 169.7, 80.5, 69.0, 48.4, 26.1.…”

Synthesis of Brominated Lactones Related to Mycalin A: Selective Antiproliferative Activity on Metastatic Melanoma Cells and Inhibition of the Cell Migration

“…In this context, it is to be noted that the bromination of D-xylonolactone ( Scheme 1 ) only leads to the 4R isomer 5 , and consequently, only its 4R derivatives 4 and 6 – 9 ( Scheme 1 and Scheme 2 ) could be obtained from it. On the other hand, the bromination of D-ribonolactone is reported [ 11 , 14 , 15 ] to give the three isomeric dibrominated compounds 10 (2S,4S, major), 11 (2R,4S, minor), and 12 (2S,4R, minor) ( Figure 6 ). Therefore, this process was expected to provide us with three out of the four possible isomers of 5 involving the C-2/C-4 centres, allowing us to study the effect of the stereochemistry of the lactone ring on the antiproliferative activity.…”