TECHNOLOGY FOCUS - ORGANIC CHEMISTRY - Preferred Process: The step of converting (V) comprises: reacting (V) with substituted 9H-purin-2-ylamine compounds of formula (A) to give substituted 4-(2-amino-purin-9-yl)-2-hydroxymethyl-3-methylene-cyclopentanol compounds of formula (VI) and de-protecting (VI) to obtain entecavir. The reaction of (V) and (A) to make (VI) is a Mitsunobu reaction carried out in the presence of a reagent including diethyl azodicarboxylate and/or diisopropyl azodicarboxylate, a trisubstituted phosphine, and organic solvent. (A) is prepared by reacting 6-substituted purine compound of formula (A1) with an amino protecting reagent in an organic solvent at a temperature of -60 degrees C to reflux to give (A). (VI) is isolated from a mixture formed from the reaction of (V) and (A) by crystallization. (V) is prepared by reducing protected (3aS,4R,5S,6aR)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta(b)furan-2-one compounds (I) to give protected (3aS,4R,5S,6aR)-4-(hydroxymethyl)hexahydro-2H-cyclopenta(b)furan-2,5-diol compounds (II), and converting (II) to give (V). The process of making entecavir further comprises: isolating (V) from a mixture resulted from the converting step by crystallization; and isolating (I) from a mixture resulted from the reaction of converting (+)-Corey diol to (I) by crystallization. The step of converting (II) to give (II) comprises oxidizing (II) to obtain protected formic acid (1R,3R,4S)-4-hydroxy-3-hydroxymethyl-2-methylene-cyclopentyl ester compound of formula (I-a), and converting (I-a) to (V). The step of converting (II) to give (V) comprises: dehydrating (II) to give protected (3aS,4R,5S,6aR)-4-(hydroxymethyl)-4,5,6,6a-tetrahydro-3aH-cyclopenta(b)furan-5-ol compounds of formula (III); oxidizing (III) to obtain protected (1R,2S,3R,4S)-2-formyl-4-hydroxy-3-(hydroxymethyl)cyclopentyl formate compounds of formula (III-a); reducing (III-a) to give protected (1R,3S,4R,5R)-4,5-bis(hydroxymethyl)cyclopentane-1,3-diol compounds of formula (IV); and dehydrating (IV) to give (V). The step of dehydrating (IV) to (V) comprises: converting (IV) to give substituted (1R,3S,4R,5S)-4-(hydroxymethyl)-5-methylcyclopentane-1,3-diol compounds of formula (V-a); removing the leaving group of (V-a) to give protected (1R,3S,4R)-4-(hydroxymethyl)-5-methylenecyclopentane-1,3-diol compounds of formula (V-c); and deprotecting (V-c) to obtain (V). (I) is prepared by converting (+)-Corey diol to (I). The step of converting (II-a) to (VII) comprises hydrolyzing (II-a). The step of oxidizing and the step of converting (II-a) to (VII) are carried out in one pot. (VII) is further converted to an antiviral drug, preferably to entecavir. The oxidizing step is carried out in the presence of an oxidizing agent including lead(IV) acetate/copper(II) chloride, iodo-benzene diacetate/copper(II) chloride, lead(IV) acetate, copper(II) bromide, iodo-benzene diacetate/copper(II) bromide, lead(IV) acetate/copper(II) iodide, iodo-benzene diacetate/copper(II) iodide, lead(IV) acetate/copper sulfate, iodo-benzene diacetate/copper sulfate, iodine/2,2'-azobis(2-methylpropionitrile) (AIBN), iodo-benzene diacetate/iodine/AIBN, manganese(II) acetate, ceric ammonium nitrate, iron(III) acetate, iodo-benzene diacetate, Dess-Martin periodinane and/or 2-iodoxybenzoic acid. Preferred Components: (V) is (4aR,6R,7aS)-2-methyl-5-methylenehexahydrocyclopenta(d)(1,3)dioxin-6-ol, (4aR,6R,7aS)-5-methylene-2-phenylhexahydrocyclopenta(d)(1,3)dioxin-6-ol or (4aR,6R,7aS)-5-methylenehexahydrocyclopenta(d)(1,3)dioxin-6-ol.R1 = halo, alkyl, cycloalkyl, aralkyl, aryl, alkoxy, thioalkyl, thio or OH;R2, R3 = H or amino protecting group; andL = leaving group. ACTIVITY - Virucide.    MECHANISM OF ACTION - None given.    EXAMPLE - Solution of (1R,3R,4S)-4-(methoxymethoxy)-3-((methoxymethoxy)methyl)-2-methylenecyclopentanol (100 mg), triphenylphosphine (225.6 mg) and N2- tert-butyloxycarbonyl-2-amino-6-iodopurine (310.6 mg) in tetrahydrofuran (5 ml) was stirred for 30 minutes at 0 degrees C. Then diethyl azodicarboxylate (150 mg) was slowly charged into the reaction solution at 0 degrees C. The resultant reaction mixture was warmed and stirred for 2 hours. Then the reaction solution was concentrated to dryness to give crude oil, which was purified to obtain tert-butyl 6-iodo-9-((1S,3R,4S)-4-(methoxymethoxy)-3-((methoxymethoxy)methyl)-2-methylenecyclopentyl)-9H-purin-2-ylcarbamate. Then the solution of tert-butyl 6-iodo-9-((1S,3R,4S)-4-(methoxymethoxy)-3-((methoxymethoxy)methyl)-2-methylenecyclopentyl)-9H-purin-2-ylcarbamate (100 mg) and sodium hydroxide (10%, excess) in dioxane/tetrahydrofuran (1:9, 5 ml) was stirred for 12 hours at 50-60 degrees C. The reaction mixture was quenched with saturated ammonium chloride, and ethyl acetate was added twice for extraction. The organic layer was combined and concentrated to dryness to give crude solid. The solid was purification to obtain entecavir (yield 50 g).