A 5‘-(Trifluoromethyl)anthracycline Glycoside:  Synthesis of Antitumor-Active 7-O-(2,6-Dideoxy-6,6,6-trifluoro-α-l-lyxo-hexopyranosyl)adriamycinone

Abstract

7-O-(2,6-Dideoxy-6,6,6-trifluoro-alpha-L-lyxo-hexopyranosyl)adriam ycinone (3), whose substituent at C-5' is a lipophilic trifluoromethyl group, has been prepared by coupling of 3,4-di-O-acetyl-2,6-dideoxy-6,6,6-trifluoro-alpha-L-lyxo-hexopyran osyl bromide (20) with 14-O-(tert-butyldimethylsilyl)adriamycinone under the Koenigs-Knorr conditions. The key step in this synthesis was the C-trifluoromethylation of 5-O-acetyl-2,3-di-O-benzyl-4-deoxy-aldehydo-L-erythro-pentose (10), derived from D-lyxose in 10 steps, with (trifluoromethyl)trimethylsilane in the presence of tetrabutylammonium fluoride, whereupon 1,1,1-trifluoro-L-arabino-hexitol (11) was obtained along with its 2-epimer. The synthetic product 3 showed remarkable antitumor activity in vivo in a low dose range compared to the analogs including doxorubicin. The fact may be ascribed to the presence of a trifluoromethyl group at C-5', suggesting the importance of the group in view of biological activity.

Production of natural and rare pentoses using microorganisms and their enzymes

“…Derivatives of rare sugar have also been used as anti-hepatitis B virus and human immunodeficiency virus (HIV) agents (Beach et al 1992;Tianwei et al 1996). As antitumor agents, such as bleomycin (Oshitari et al 1997), are active against several *Corresponding author murine tumors and making them useful for cancer treatment (Morita et al 1996;Takagi et al 1996). Recently, researchers have found many important applications of Larabinose in medicine as well as in biological sciences.…”

“…Starting materials for the production of antitumoral and immunosti mulatory galactosylcer-amide agents, against several murine tumors; useful for cancer therapy Morita et al 1996;Takagi et al 1996 Starting materials for the production of two rare aldohexoses, L-allose and L-altrose Austin and Humoller, 1934b L-ribose Use as a potent anti-Hepatitis B virus (HBV) and anti-Epstein Barr virus (EBV) agents Tianwei et al 1996 L-xylulose Potential inhibitors of various glycosidase Levin et al 1995 Starting material for the synthesis of antitumor agents Yoshikawa et al 1993 Starting material for the synthesis of dehydroamino acid derivatives, act as azinomycin antitumor antibiotics Moran et al 1993 Production of D-erythroascorbic acid and oxalic acid Loewus et al 1995 D-arabinose Synthesis of maytansinoid model compounds with significant anti-cancer activity Goodwin et al 1998 Starting material for the synthesis of 9-(2-deoxy-2-fluro-β-L-ara binofuranosyl) purine nucleosides with anti-hepatitis B virus activity Ma et al 1997 L-xylose Starting materials for the synthesis of Lribofuranose derivatives Chelain et al 1995 …”

Inhibitory Effects of D-mannose onStreptococcus mutansin the Presence of Sucrose

“…D-xylose, a rare aldopentose, can be converted to xylitol by D-xylose reductase in many yeasts such as Candida tropicalis (7,8). D-lyxose is a C-2 epimer of D-xylose, and is used as a starting material for antitumor and immunostimulatory agents (9). D-lyxose can be produced from xylulose by lyxose isomerase (10).…”

Synthesis of disubstituted- and deoxydisubstituted- derivatives of α-D-xylofuranose as anticancer agents

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] Among them, several branched-chain sugar derivatives, [11][12][13][14][15] as well as some low molecular weight sugar derivatives with aminoalkyl appendages, [1][2][3][4] have shown potent anticancer activity. In continuation of our efforts to find potent anticancer agents and on the basis of the correlation of anticancer activity in vitro, in vivo, and lipophilicity of the compounds of our previous work on aminoalkyl derivatives of sugars, 4,16 we have synthesized disubstituted-and deoxydisubstituted-derivatives of α-D-xylofuranose and evaluated them for anticancer activity.…”