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

Several disubstituted-and deoxydisubstituted-derivatives of α - D -xylofuranose have been synthesized and evaluated on various in vitro human cancer cell lines. In primary in vitro screening, seven derivatives expressed anticancer activity

The key intermediate 6 was further used to synthesize different 3-O-{3′-(decyloxy)propyl}-5deoxy-5-(substituted)-α-D-xylofuranoses (9a-m) via tosylation of the primary alcohol (5-OH) by p-toluenesulphonyl chloride in pyridine at 0 o C followed by displacement of the tosylate group with various primary and secondary amines as shown in Scheme 1.The structures of all these compounds were determined on the basis of complementary spectroscopic ( 1 H NMR and MS) and analytical data (cf.experimental section).

Pharmacological Evaluation
Several compounds were submitted to the National Cancer Institute (Bethesda, MD) for screening.For primary in vitro screening, compounds 7a-h and 9a-m were evaluated for their cytotoxic potency on three human cell lines (NCI-H460 lung cancer, MCF7 breast cancer and SF-268 CNS cancer).A compound is considered to be active when it reduces the growth of any of the cell lines to 32% or less.Among them, seven compounds (7a, 7b, 7c, 7f, 7g, 9c and 9h) were found active (concentration 10 -4 M) in primary screening.Details of this in vitro test method and the information, encoded by the activity pattern over all cell lines, have been previously reported. 18Further investigation is in progress.
In summary, a series of disubstituted-and deoxydisubstituted-derivatives of α-Dxylofuranose was synthesized and evaluated for anticancer activity.The first results confirm the validity of our approach providing practical access to α-D-xylofuranose based derivatives possessing in vitro antiproliferative activity against human tumor cells.Evaluation of compounds 7a, 7b, 7c, 7f, 7g, 9c and 9h on a full panel of 60 human cancer cell lines is underway and the results will be disclosed in due course.
in good yield.

ARKIVOC 2005 (i) 65-74 ISSN 1424-6376 Page 68
Melting points were determined in open capillaries on a Büchi B-545 melting point apparatus.Compounds were routinely checked for their purity on silica gel 60 F 254 TLC plates and their spots were visualized by exposing them to iodine vapors or by charring the plates with 5% H 2 SO 4 -EtOH reagent or by spraying the plates with Dragendorff′s reagent.IR spectra were recorded on a Perkin-Elmer spectrum RX series FT-IR spectrophotometer.1HNMR spectra were recorded on a Bruker Advance DRX 200 MHz instrument as solutions (in CDCl 3 ) using TMS as internal reference, and chemical shifts values are expressed in δ units.Mass spectra were run on an Applied Biosystems API 3000 instrument using direct inlet system under positive ion electrospray ionization source.Elemental analyses were carried out with a Perkin Elmer 2400 analyzer and the values found were within ±0.4% of theoretical values.