Synthesis of -difluorosaccharides

Potential antitumor agents. 58. Synthesis and structure-activity relationships of substituted xanthenone-4-acetic acids active against the colon 38 tumor in vivo

“…Published structure-activity relationships for the colon 38 activity of analogues of flavoneacetic acid (1) show that, while there is some latitude for substitution at the 2position (the 2-phenyl, 2-benzyl, and 2-furyl compounds 2-4 are all active), there seemed to be a definite requirement for placement of the acetic acid side chain, with the 8-isomer being active but the 6-isomer inactive.2 Thus we first studied the set of isomeric xanthenoneacetic acids (5)(6)(7)(8), in which the 2-phenyl ring of flavoneacetic acid is fused to the chromone ring rather than pendant to it. The 1-, 2-, and 4-acetic acid derivatives (5, 6, and 8) have been prepared previously and evaluated as antiinflammatory agents.10 These compounds proved considerably more lipophilic than flavoneacetic acid (lipophilicity was mea- sured by thin-layer liquid-liquid chromatography, as described previously19), with Rm values of 0.5-0.6, compared to that of 0.06 for 1. While the 1-, 2-, and 3-acetic acids…”

“…There has recently been much interest in the drug flavoneacetic acid (FAA: NSC 347512) (1) following initial reports1,2 of its unusual spectrum of anticancer activity. While possessing very limited in vivo activity against P388 and other leukemia models, it is curative against the colon 38 adenocarcinoma and is active in a variety of other colon and pancreatic tumors that are very resistant to most chemotherapeutic agents.3,4 Additionally, 1 has a different toxicity profile to most anticancer drugs, with no significant myelosuppression observed.1 2345 The unique therapeutic and toxicity profiles of 1 suggest it has a novel mechanism of action, but this has not yet been elucidated.…”

Chapter 14. Biological chemistry. Part (i) Monosaccharides

“…Their general findings are illustrated by the conversion of 1,2 : 3,4-di-O-isopropylidene-6-O-methyl-a -D-galactopyranose into the (E)and (2)-isomers of the unsaturated polyol (72). Abstraction of the anomeric proton is thought to initiate this transformation and the anion (69) so formed subsequently rearranges with loss of acetone to (70), which then eliminates another acetone molecule to give, after protonation at 0 -4 , the unsaturated lactone (71). Further attack on (71) gives the isomeric products ( 72 The synthetic, value of this reaction has been studieds9 with methyl 2,3-0benzylidene-a -L-rhamnopyranoside (73) and its 4-0-methyl derivative (74).…”

Synthesis of 3-deoxy-3,3-difluoro-d-ribohexose from gem-difluorohomoallyl alcohol

“…Although monofluorinated [3] and trifluoromethylated sugars [4] have been well studied, only a few gem-difluoromethylenated sugars have been reported, which is probably due to the shortcomings of existing synthetic methods. 2-Deoxy-2,2-difluorinated sugars were obtained either by electrophilic fluorination of 2-fluoroglycals [5] and by reaction of carbonyl groups with DAST [6]. The difluorination at the 4-keto-and 3-keto-groups with DAST for synthesis of the corresponding 4-deoxy-4,4-difluorinated [7] and 3-deoxy -4,4-difluorinated [8] sugars have been described.…”