Scheme III TBAF = (n-Bu)4NF Synthesis of /S-Furanone 2. Compound 1 (226 mg, 1 mmol) was dissolved in 8 mL of anhydrous diethyl ether, placed in a flask equipped with a dry argon inlet, and cooled at -15 °C. To the stirred solution was added 0.63 mL (1 mmol) of a 1.60 M ethereal solution of methyllithium. After 1.30 h at -15 °C, 1.5 mL of anhydrous hexamethylphosphoric triamide and 0.7 mL (8.8 mmol) of freshly distilled chloroacetyl chloride were added. The mixture was reacted 30 min at -15 °C and 1 h at room temperature.The reaction mixture was poured into a slurry of ammonia and crushed ice, stirred for 20 min, and then extracted three times with 20 mL of diethyl ether. The combined extracts were washed with water and dried (Na2S04). After evaporation at reduced pressure, 200 mg of product was obtained which was chromatographed on a Florisil (6 g) column. By elution with n-pentaneethyl acetate (95:5 v/v) there was obtained 160 mg (82% yield) of pure 2: oil; IR (liquid film) 1700,1640 cm"1; NMR (CDC13)4.50 (s, 2 H, OCH2CO), 0.95 (s, 9 H, (CH3)3C).

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The nucleotide analog 7-deazaguanosine has not previously been reported to possess biological (antiviral or antitumor) properties in cell culture or in vivo. Up to 10(5) U of interferon per ml was detected in mouse sera 1 to 4 h following oral (200-mg/kg of body weight) and intraperitoneal (50-mg/kg) doses of the compound. 7-Deazaguanosine also caused significant activation of natural killer and phagocytic cells but did not augment T- and B-cell blastogenesis. Intraperitoneal treatments of 50, 100, and 200 mg/kg/day administered 24 and 18 h before virus inoculation were highly protective in mice inoculated with lethal doses of Semliki Forest or San Angelo viruses. Less but still significant survivor increases were evident in treated mice infected with banzi or encephalomyocarditis viruses. In most cases, the degree of antiviral activity was similar to that exhibited by the biological response modifier 7-thia-8-oxoguanosine. 7-Thia-8-oxoguanosine was more potent than 7-deazaguanosine against encephalomyocarditis virus in mice, however. Oral efficacy was achieved with 7-deazaguanosine treatments of greater than or equal to 100 mg/kg against all virus infections, whereas 7-thia-8-oxoguanosine is reported to be devoid of oral activity in rodents. Thus, 7-deazaguanosine represents the first reported orally active nucleoside biological response modifier exhibiting broad-spectrum antiviral activity against particular types of RNA viruses.

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