MXPA01003168A

MXPA01003168A - Antiviral purine derivatives

Info

Publication number: MXPA01003168A
Application number: MXPA/A/2001/003168A
Authority: MX
Inventors: Christopher Mcguigan; Jan Balzarini
Original assignee: Rega Foundation; University College Cardiff Consultants Limited
Priority date: 1998-09-28
Filing date: 2001-03-27
Publication date: 2002-05-09

Abstract

Chemical compounds comprising nucleoside phosphoramidates, their preparation and their therapeutic use in treating viral infections, particularly HIV and HBV are disclosed. The compounds contain a substituted adenine analogue moiety comprising 2-amino-6- (cyclopropylamino)-9 H-purin-9-yl. The compounds show both anti-viral activity and acid stability. Salts and esters of the phosphoramidates are included. A representative compound is (1S, 4R), -4-[2-amino-6- (cyclopropylamino) -9H-purin-9-y1]-2-cyclopentene-1- methanol O-[phenyl- (methoxy -L-alaninyl)]- phosphate.

Description

PURINE ANTIVIRAL DERIVATIVES DESCRIPTION OF THE INVENTION The present invention relates to a chemical compound f. In particular, the present invention relates to a chemical compound suitable for use as an antiviral agent. The present invention is reframed In addition to the therapeutic use of the present chemical compound, a pharmaceutical composition containing the The present compound and the use of the present compound in the manufacture of a medicament. From the knowledge of acquired human immunodeficiency syndrome (AIDS), much interest and research activity has been directed to its knowledge and to try to provide a measure of treatment. The human immunodeficiency virus (HIV) has been identified as a presumed etiological agent in AIDS. There is currently an extensive bibliography related to the use of a wide range of chemical compounds that aim to demonstrate their antiviral activity with respect to HIV, hepatitis B virus (HBV), herpes and other viruses. A class of compounds that has demonstrated antiviral activity and which has been the subject of a great research effort are the nucleoside analogues.

REF.128173 An example of said compound is "Abacavirj which is a substituted adenine analogue (Foster RH &Faulds D. Drugs 1998 55 729-736) .This compound has been included in the clinical use due to the possible activity and stability of the compound shown in the preliminary disclosures PCT / GB96 / 00580 refers to a class of nucleoside analogues that are said to be very active with respect to HIV In particular, PCT / GB96 / 00580 addresses the problem of providing compounds that are said to be very potent viral inhibitors in vi tro in TK ~ and TK * cells The compounds described in PCT / GB96 / 100580 are phosphoramidates of nucleoside analogs purine, or pyrimidine. , they can present chemical instability, for example, in acids, or biological, for example, to the nucleoside phosphorylase, towards the breakdown of the glycosidic bond, the consequent deactivation can limit their clinical efficacy. However, a compound that is potentially useful in a clinical setting needs to present a number of other properties, in addition to demonstrating, at least in the in vitro trials, sufficient and desired antiviral activity. First, these other properties include good pharmacokinetic properties, sufficient stability in the compound that allows easy handling and availability, and a sufficiently low toxicity that allows its administration with an acceptable level of side effects to a patient in need of treatment. the viral infection in question. However, in practice it is frequently found that attempts to modify a compound demonstrating an antiviral activity in order to improve the rest of the properties, may have a detrimental effect of the antiviral activity that said compound exhibits. . Ideally, it is also that any compound proposed for clinical trials also has an easy means of administration and can be prepared by an economically viable route. It is an object of the present invention to provide a new class of compounds which exhibit potent activity, at least against HIV, combined with good pharmacokinetic and stability properties and which exhibit a sufficiently low toxicity to provide a compound having beneficial properties for its clinical use According to the present invention, | a compound according to the following formula (I) is provided: wherein Ar is an aryl group, R1 and R2 are independently selected from the group consisting of H, alkyl and aryl groups; X is selected from the group consisting of O, NH, NR4? And S, R4 being selected from the group consisting of alkyl and aryl groups; R5 is selected from the group consisting of H, alkyl and aryl groups, and may, when each of R1 and R5 is alkyl, these be linked to form a 5-membered ring; and R3 is selected from the group consisting of H, alkyl, aryl, heterocyclic and polycyclic groups; or one of its pharmaceutically acceptable derivatives or metabolites. The present invention includes physiologically functional salts and derivatives of the compounds! here defined. The reference herein to an alkyl group means a saturated or unsaturated (for example alkenyl or alkynyl), cyclic or acyclic, branched or unbranched hydrocarbyl radical. When cyclic, the alkyl group is preferably C to C 2, more preferably C 5 al Cio, more preferably C 5 to C 7. When it is acyclic, the alkyl group is preferably Ci a Cie, > more preferably Ci to Cd, more preferably, methyl or ethyl. The reference herein to an aryl group means an aromatic group, such as phenyl or naphthyl, or a heteroaromatic group containing one or more, preferably a, heteroatom, for example, O, N and / or S, such as pyridyl, pyrrolyl, furanyl or thiophenyl. Preferably], the aryl group comprises phenyl or substituted phenyl.

The alkyl and aryl groups may be substituted or unsubstituted, preferably unsubstituted. When substituted, there will usually be 1 to 3 substituents, preferably 1 substituent. The substituents may include halogen atoms and halomethyl groups such as CF3 and CC13; oxygen-containing groups such as oxo, hydroxy, carbojfi, carboxyalkyl, alkoxy, alkoyl, alkoxy, aryloxy, aryloyl and aryloyloxy; nitrogen-containing groups such as amino, alkylamino, dialkylamino, cyano, azide and nitro; sulfur-containing groups such as thiol, alkylthiol, sulfonyl and sulfoxide, heterocyclic groups which may be substituted; alkyl groups, which may be substituted; and aryl groups, which may be substituted, such as phenyl and substituted phenyl. Alkyl includes substituted and unsubstituted benzyl. The reference in the present specification to alkoxy and aryloxy groups means alkyl-O- and aryl-O- groups, respectively. The reference to alkoyl and aryloyl groups means alkyl-CO- and aryl-CO-, respectively. The reference in the present specification to heterocyclic groups means groups containing one or more rings, optionally bridged, containing 1 to 16 heteroatoms in total. Each ring in the group may contain 3 to 12, preferably 1 to 6, atoms in total. At least one ring present contains 1 to 2 heteroatoms. When two or more rings are present, they may be condensed or uncondensed. The rings may contain unsaturations. The heteroatoms include 0, S and N. Examples of such heterocyclic groups containing one or more pyrrolid, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, pyrrolidinyl, pyrrolinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, tetrahydrofuranyl, pyranyl, pyrryl , pyridyl, pyrazinyl, pyridazinyl, piperidyl, piperazinyl, morpholinyl, thionaphthyl, benzofuranyl, isobenzofuryl, indolyl, oxyindolyl, isoindolyl, indazolyl, indolinyl, 7-azaindolyl, isoindazolyl, benzopyranyl, coumarinyl, isocoumarinyl, quinolyl, isoquinolyl, naphtridinyl, cinolinyl, quinazolinyl, pyridopyridyl, benzoxazinyl, quinoxadinyl, chromenyl, chromanyl, isochromanyl and carbolyl The reference herein to polycyclic groups means a group comprising two or more carbocyclic or non-aromatic heterocyclic rings which may be substituted. Preferably, the group contains 2 a, 4 condensed or non-condensed rings (fused) two 'or not fused), each of which adequately contains 3 to 12 atoms, more suitably 4 to 10J more suitably 5 to 7, and even more suitably 5 to 6 atoms. The definitions of cyclic alkyl and heterocyclic rings given above also apply to the rings in the polycyclic groups. The reference in the present specification to halogen means a fluorine, chlorine, bromine or iodine radical, preferably a fluorine or chlorine radical. The group Ar comprises a substituted or unsubstituted aryl group, the term "aryl group" being and the possible substitution of the group as defined above.

Preferably, Ar is a substituted or unsubstituted phenyl group. Particularly preferred substituents are electron acceptor groups such as halogen (preferably chlorine or fluorine), trihalophoryl or (preferably trifluoromethyl), cyano and preferably, Ar is phenyl, 3,5-dichloro-phenyl, p-trifluoromethyl-phenyl, p-cyano-phenyl or p-nitro-phenyl. R3 is selected from hydrogen, alkyl, aryl, heterocyclic and polycyclic groups. Preferably, R is a substituted or unsubstituted alkyl group. Preferably, R3 is a C?-6 alkyl group, substituted or unsubstituted, more preferably, an ethyl or methyl group. Preferably, at least one 'of R1 and R2 is hydrogen. It will be appreciated that if R1 and R2 are different, the carbon atom to which they are attached is an asymmetric ash. Preferably, this carbon atom is chiral. When this carbon atom is chiral, the stereochemistry of this site may be D or L or mixed, the stereochemistry being preferred L. R5 and R1 may be bonded to form an alkylene bridge comprising 3 to 4 carbon atoms, so as to form a ring of 5 or 6 links. Preferably, R5 is hydrogen. It will be appreciated that the -NH-CHR 1 -'C02R3 group corresponds to an α-amino acid with the protected carboxyl. Preferably, the group R1 corresponds to the side chain of a natural amino acid such as Alanine, Arginine, Asparagine, Aspartic Acid, Cysteine, Cystine, Glycine, Glutamic Acid, Glutamine, Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Proline, Serine, threonine, tryptophan, tyrosine, valine. Preferably, R1 is Me or PhCH2 which correspond to the side chain of alanine or phenylalanine, respectively. Preferably, the stereochemistry at the asymmetric center -CHR1- corresponds to an L-amino acid. A quality of the aryl ester phosphate compounds of the present invention is that they have a significantly improved antiviral efficacy in in vitro tests in comparison to their corresponding nucleoside analog, (IS, 4R) -4- [2-aminp- 6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol, which is known as Abacavir and which has the following structural formula: According to another aspect of the present invention, a compound of formula (II) is provided: M wherein R1, R2, R3, R5 and X are as defined above, or one of their pharmaceutically acceptable derivatives or metabolites. Preferably, X is O. The intracellular generation of antiviral metabolisms is an important feature of the invention for various reasons. In cases where the nucleoside is not a good substrate for the host nucleoside kinases, the activation will be poor and the antiviral efficacy will be low, even if the triphosphate is an excellent RT inhibitor. In such cases, the generation of the present metabolites can lead to a very significant improvement of the antiviral action. By "pharmaceutically acceptable derivatives" is meant any pharmaceutically acceptable salt, ester or ester salt or any other compound which, after administration to a receptor, can provide (directly or indirectly) a compound of the present formula or the present metabolite. "Pharmaceutically acceptable derivatives" include the sodium, succinate, fumarate, glutarate and D-tartrate salts. By "pharmaceutically acceptable metabolite" is meant a metabolite or residue or residue of a compound of the present formula or of the present metabolite which causes the inhibition of the reverse transcriptase shown by the present compounds. According to another aspect of the present invention, there is provided a compound according to the present invention for use in a method or treatment method, preferably in the prophylaxis or treatment of a viral infection. According to another aspect of the present invention, there is provided the use of a compound (according to the present invention in the manufacture of a medicament for the prophylaxis or treatment of a viral infection.) In accordance with another aspect of the present invention, a method is provided. of prophylaxis or treatment of a viral infection comprising administering to a patient in need of such treatment an effective dose of a compound according to the present invention.V viral infection can comprise any viral infection such as HIV and herpes virus, including HSV 1 and HSV 2, CMV, VZV, EBV, HAV, HBV, HCV, HDV, HHV6, HHV7, HHV8, papilloma, adenovirus, rabies and influenza Preferably, the viral infection comprises HIV or HBV infection, more preferably HIV-I or HIV-II A quality of the present invention is that the compounds exhibit a good activity against HIV-I and HIV-II and HBV, In accordance with another aspect of the present invention, a pharmaceutical composition comprising a compound of the present invention combined with a pharmaceutically acceptable excipient. According to another aspect of the present invention, there is provided a process for preparing a pharmaceutical composition comprising the step of combining a compound of the present invention cc > n a pharmaceutically acceptable excipient. The compounds of the present invention can demonstrate significant stability towards decomposition by acid-induced hydrolysis. | The present compounds can therefore be particularly suitable for oral administration | low • - • • • • • • • • Typical dosage conditions in humans since these can maintain stability under the highly acidic environment of the stomach. Since the purine in the compounds of formula (I) is a weak base (pKa = 5.0) and the compounds of formula (I) demonstrate acid stability, salts of the compounds of formula (I) can be formed with acids, such as carboxylic acids and dicarboxylic acids. Such salts may be stable crystalline solids, which may be beneficial in terms of shelf life of improved storage and ease of handling during manufacture in the form of pharmaceutical compositions. Preferred carboxylic and dicarboxylic acids include malonic, succinic, glutaric, fumaric and tartaric acids. In contrast to the salts of the compounds of formula (I), the free bases of the compounds of formula (I) can be in a non-crystalline amorphous form which can be hygroscopic. The P-OH group of the compounds of formula 1 (II) is a weak acid and can therefore form monobasic salts with bases providing, for example, sodium, potassium, ammonium and triethylammonium salts. In the compounds of formula (II), when X is OH, dibasic salts can be formed. Such dibasic salts can be in the form of stable solids, which can provide improved storage shelf life benefits and ease of handling during manufacture in the form of pharmaceutical compositions. The compounds of the present invention can also demonstrate better stability in biological media, for example, in human plasma. The longer storage life of the compounds of the present invention in media such as human plasma may involve a pharmacokinetic advantage in dosing to humans in need of treatment. The medicament employed in the present invention can be administered by the oral or parenteral routes, including intravenous, intramuscular, intraperitoneal, subcutaneous, transdermal, air (aerosol), rectal, vaginal and topical administration (including buccal and sublingual). For oral administration, the compounds of the invention will generally be provided in the form of tablets or capsules, such as powders or granules, or in aqueous solution or suspension. Tablets for oral use may include the active ingredients blended with pharmaceutically acceptable excipients such as inert diluents, disintegrating agents, binding agents, lubricating agents, sweetening agents, flavoring agents, coloring agents and preservatives. Suitable inert diluents include sodium and calcium carbonate, sodium and calcium phosphate and lactose, while corn starch and alginic acid are suitable as disintegrating agents. The binding agents may include starch and gelatin, while the lubricating agents, if present, will generally be magnesium stearate, stearic acid or alkano. If desired, the tablets can be coated with a material such as glyceryl monostearate and glyceryl distearate, to delay absorption in the gastrointestinal tract. Capsules for oral use include hard gelatin capsules in which the active ingredient is mixed with a solid diluent, and soft gelatin capsules in which the active ingredients are mixed with water or an oil such as peanut oil, liquid paraffin or olive oil. Formulations for rectal administration may be presented in suppository form with a suitable base composed, for example, of cocoa butter or a salicylate. Formulations suitable for vaginal administration may be presented in the form of weights, ... ¡. .. Are tampons, creams, gels, ointments, foams or spray formulations containing, in addition to the active ingredient, vehicles such as are known in the art. For intramuscular, intraperitone, subcutaneous and intravenous use, the compounds of the invention will generally be provided in sterile aqueous solutions or suspensions, buffered to an appropriate IpH and isotonicity. Suitable aqueous vehicles include Ringer's solution and isotonic saddic chloride. The aqueous suspensions according to the invention can include suspending agents such as cellulose derivatives, sadist alginate, polyvinylpyrrolidone and gum tragacanth and a wetting agent such as lecithin. Suitable preservatives for aqueous suspensions include ethyl p-hydroxybenzoate and n-propyme. The compounds of the invention can also be presented in the form of formulations 1 in liposomes. In general, a suitable dose will vary in the range of 0.01 to 10 mg per kg of receptor body weight per day, preferably in the range of 0.2 to 1.0 mg per kg of body weight per day. The desired dose is preferably presented once a day, although they may ¿JJ ^^ l ^ já ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ ^ administer doses as two, three, four, five or six or more sub-doses at appropriate rvals throughout the day. These sub-doses may be administered in unit dosage form, for example, containing 10 to 1500 mg, preferably 20 to 1000 mg, and most preferably 50 to 700 mg of active ingredient per unit dosage form. According to another aspect of the present invention, there is provided a process for preparing the present compound, which comprises reacting a compound of formula with a compound of formula OR II ArO-P-CI N- Rd CR1R2 COXR3 - • "* '" *' - in which R1, R2, R3, R5 and X have the meanings indicated above. The reaction can be carried out under dry conditions at room temperature in tetrahydrofuran in the presence of N-methylimidazole, or using t-butyl magnesium chloride and an excess of the appropriate phosphoroclorbate reactant. Embodiments of compounds of the present invention can be prepared in which Ar has been replaced by H from the acid form by treating the ester with an aqueous base. Compounds in which X is NH or NR4 can be prepared by treating the acid form (X = O1 and R3 = H) with ami.na. The above starting material, (ÍS, 4R) r4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol, is known as Abacavir | and can be prepared by any method known in the art, for example, by the procedures described in European Patent Specification Number 0434450. in PCT Patent Application No. PCT / GB95 / 02014 and in the Patent Application. PCT No. PCT / EP98 / 02835, which are all incorporated by reference.

The invention will be described below with reference to the following examples. It will be appreciated that the following will be rpreted merely by way of example and that modifications to the details may be made, all within the scope of the invention.

EXPERIMENTAL PROCEDURES General procedures The following solvents and anhydrous reactants were purchased from Aldrich with perfectly closed stoppers: Dichloromethane (DCM), diethyl ether (Et20), tetrahydrofuran (THF), Nfinethyl imidazole (NMl), methanol (MeOH), dimethylformamide (DMF), pyridine. (pir), dioxane and tBuMgCl. Dry the triethylamine (NEt3) by refluxing over CaH2 for several hours and separating by distillation for immediate use.

Chromatography Thin film chromatography (tic) was performed on commercially available Kieselgel 60F254 'Merck plates and the separated components were visualized using ultraviolet light (254 nm and 366 nm) or by treatment with 5% ethanolic acid solution. molybdophosphoric (MPA), followed by heating. Column chromatography was performed using Woelm silica (32 to 63 mm) as the stationary phase Spectral characterization All NMR spectrum data, unless indicated otherwise, were obtained in CDCI3. Proton nuclear magnetic resonance and Carboho ^ -13 were recorded on a Bruker Avance DPX30p spectrometer with operating frequencies at 300 MHz and 75 MHz, respectively. The phosphorus-31 NMR spectra were recorded on a Bruker Avance DPX3 spectrometer operated at 121 MHz and expressed in units with respect to 85% phosphoric acid as an external standard, with positive displacements under the field. The following abbreviations are used in the naming of the NMR signals: s (singlet), d (doublet), t (triplet), q (quadruple), m (multiplet), bs (broad signal), dd (two doublets), dt (two triplets). The low resolution mass spectra were executed in a VG Platform II Fisons apparatus (Fi'sons, Altrincham, United Kingdom) (ionization spectrometry at atmospheric pressure and electronebulization mass) in negative or positive ion mode.

High performance liquid chromatography (HPLC) was run on a reverse phase column SJSODS2 with a water / acetonitrile eluent. 100% water (0 minutes), 20% water (35 minutes), 20% water (45 minutes), 100% water (55 minutes) with a flow rate of 1 ml / min and UV detection at 254 nm . Patterns: acetone (t R 4.54 minutes), toluene (tR 10.21 minutes). The final products showed purities greater than 99%, with undetectable amounts of the starting nucleoside.1 Nomenclature and Numbering of the Compounds The nomenclature of the IUPAC is used as much as possible, although for convenience, most of the compounds were abbreviated. The numbering is the conventional numeration of the nucleosides.

"- •" "• Standardized procedures For practical purposes, standardized procedures are given when applicable.

Standard procedure 1 Thionyl chloride (2 eq mol), gq > dropwise at 0 ° C to a stirred solution of anhydrous alcohol (10 eq. mol), and the resulting solution was stirred for 1 h. After reaching room temperature, the appropriate amino acid (1 eq mol) was added and the reaction was heated to reflux for 6-16 hours. Removal of the solvent and recrystallization from methanol: ether gave the hydrochloride salts of the amino ester.

Standard procedure 2 The appropriate amino acid (1 eq mol), para-toluene sulfonic acid (1.1 eq mol) were heated under reflux in toluene (10 [mu] l) under Dean and Stark conditions for 6 to 16 hours and the appropriate alcohol (1 eq mol). Upon cooling to room temperature, the solvent was removed under reduced pressure to provide an oil. This was solubilized in dichloromethane (50 ml) and washed with 10% K2CO3 (50 ml) and water (50 ml), filtered and the filtrate was reduced to dryness to give an oil. This was solubilized in the minimum amount of acetone and neutralized with 2M HCl and then lyophilized to yield the hydrochloride salts of the amino acid ester.

Standard procedure 3 Suspended in anhydrous dichloromethane I (3Q a 60 ml), phenyl dichlorophosphate (1 eq mol) and the hydrochloride salt of the appropriate amino acid ester (1 eq mol). Triethylamine (2 eq mol) in anhydrous dichloromethane (30 ml) was added dropwise at -80 ° C and the reaction was allowed to warm to room temperature overnight. The solvent was removed under reduced pressure and under nitrogen, yielding white solids. These were added to anhydrous ether (2 25 ml), filtered and the filtrate was reduced to dryness to provide the products as crude oils. These were stored in anhydrous THF and used without further purification.

Standard procedure 4 The (ÍS, 4R) -4- (2-aminq-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol (1 eq mol) was dried by azeotropic distillation with pyridine anhydrous (3 x 5 ml) and then suspended in anhydrous THF (5 to 30 ml). TBuMgCl (1 to 2 eq Mol, 1.0 M solution in THF) was added dropwise to the suspension and the resulting suspension was stirred for 10 minutes, i Phosphoroclorurate species (3 eq Mol, solution in THF) were added then dropwise and the resulting solution was stirred at room temperature for 24 to 96 hours. The reaction was then quenched by the addition of saturated NH 4 Cl (0.1 ml) and, after 10 minutes, the solvent was removed under reduced pressure. The crude product was purified by silica gel chromatography.

L-alanine methyl ester hydrochloride. C4H? 0O2N? Cl ?, MW = 139.38. This was synthesized according to Standard Procedure 1, using anhydrous methanol (34 ml, 0.84 mol), thionyl chloride (8.2 ml, 0.112 mol) and L-alanine (5.0 g, 0.056 mol). The product was isolated as a white solid (2.87 g, 36.7%). 2 H NMR (D20): d 4.07-4.00 (1H, q, CH, J = 7.22 Hz), 3.83 (3H, s, OCH3), 1.39-1.37 (3H, t, CH3). 13 C NMR (D20): d 171. 5 (CO), 53. 9 (O) CH 3, 49.1 (CH), 15.4 (CH3).

(Methoxy-L-alaninyl) -f-p-osphorochlorurate. C? 0H? 3O4N? Cl? P? , MW = 277. 65 This was synthesized according to Standard Procedure 3, using L-alanine methyl ester hydrochloride (2.0 g, 14.34 mmol), phenyl phosphorodichloride (3.02 g, 2.14 ml, 14.34 mmol) and anhydrous triethylamine (2.90 g, 4.0 ml, 28.68 mmol). The product (3.91 g, 98.2%) was isolated as a crude colorless oil which was stored with anhydrous THF (40 ml) providing a 0.47 M solution. 31 P NMR: d 9.28. 8.97 (1: 1). XH NMR: d 7.39-7.34 (2H, m, O'-Ph), J. 29-7.20 (3H, m, 'm' + 'p'-Ph), 4.49-4.37 (1H, q, NH¡alaJ, 4.27-4.09 (1H, m, CHala), 3.78 (3H, d, OCH3) , 1.52¡-1.49 (3H, dd, CH) • 13 C NMR: 173.6 (CO), 150.1 ('ipso'rPh), 130.25 (* m * -Ph), 126.4 (' p'-Ph), 120.9 ( O'-Ph), 53.2 (OCH3), 51.0 (CH), 20.9 (CH3ala). 0- [(1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol Cf- (phenyl- (methoxy-L-alaninyl)] -phosphate Cf 1490. C24H3o05N7P? , PM = 527.53. This was synthesized according to Standard Procedure 4, using (ÍS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-l-ethanol (500 mg, 1.75 mmol), tBuMgCl (1.0 μM solution in * "-. * -» - »-» -. I. - aA * a-THF) (1.75 ml, 1.75 mmol) and phenyl (metpxi-L-alaninyl) phosphorochloridate (0.47 M solution in THF) (11.17 mL, 5.24 mmol), in THF (30 mL) and stirring at room temperature for 70 hrs. The crude product was purified by column chromatography, eluting with 3% MEOH in DCM and then with 2% MeOH er. DCM providing the product as a white foam (442 mg, 48%). 31 P NMR (MeOH-d4): d 3.97, 3.88 1 H NMR: d 7.41 (1H, d, C8), 7.24-7.19 (2H, m, * o'-Ph), 7.13-7.03 (3H, m, m '+ * p'-Ph), 6.08 (1H !, bs, NH), 5.98 (1H, q, H2'), 5.78 (t , H3 '), 5.44 (1H, t, Hl'), 5.09 (2H, bs, NH2), 4.22-4.02 (3H, m, NHala + H5 '), 3.99-3.87 (1H, m, CHala), 3.59 (3H, t, 0CH3), 3.05 (1H, d, H4 '), 2.92 (1H, bs, CHcPr), 2.73-2.62 (1H, m, 1 of H6'), 1.62-1.53 (1H, m, 1 of H6 '), 1.30-1.25 (3H, t, CH3ala), 0.78-0.71 (2H, q, 2H of CH2cPr), 0.54-0.4 ^ (2H, t, 2H of CH2cPr). 13C NMR: d 174.6 ( CO), 160.3 (C2), 156.6 (C4), 151.3 (C6), 151.1 ('ipso'-Ph), 136 .8 (C8), 135.9 (C2 '), 131.5 (C3'), 130.0 ('m'-Ph), 125.2 Cp ^ -Ph), 120.5 (O'-Ph), 115.0 (C5), 69.2 ( C5 '), 59.2 (Cl'), 52.8 (OCH3), 50.5 (CHala), 46.0 (C4 '), 34.9: C6' 24.2 (CHcPr), 21.2 (CH3ala), 7.7 (CH2cPr). MS ES +: m / z 527.86 (100%) (M) +, 546.84 (M + K) MS FAB: For C24H3 ?? 5N7P, requires 528.212431. found 528.213848. HPLC: tR 30.33 (100%) - (100% water (0 min), 20% water (35 min), 20% water (45 min), 100% water (55 ml?). IR: 3328.6 (N-Hstr.), 2922.1, 2862.9 (C-Hstr.), 1734. 4 (C = Ostr.), 1590.9 (C aromatic Cstr.), 1462.9 (C-Hdef.), 1376.8 (-CH3sim. Def.), 1207.1 (P-O-aryl), 1154.0 (C-Ostr.), 1027.7 (P-O-alkyl), 933.4 (C-olefinic-Hdef.), 721.8 (monosubstituted aromatic C-Hdef.).

(Methosi-D-adaninyl) -phenyl phosphorochloridate C? OH? 304N1Cl? P ?, MW = 277.65. This was synthesized according to Standard Procedure 3, using D-alanine methyl ester hydrochloride (1.0 g, 7.17 mmoi), PhOP (0) Cl2 (1.51 g, 1.07 ml, 7.17 mmol) and NEt3 (1.45 g, 2.0 ml, 14.0 mmol) yielding 1.66 g (83.4%) d, the crude product which was added to anhydrous THF (101 ml), giving a solution of 0.60 mmol / ml which was used without further purification. 31P NMR: d 9.38. 9.18 (1: 1). XH NMR: d 7.39-7.30 (2H, t, "O'-Ph), 7.29-7.09 (3H, m, 'm' + 'p'-Ph), 4.85-4.80 (1H, d, NHala), a & amp; amp; j ^ A. 4. 19-4.11 (1H, m, CHala), 3.75 (3H, d, OCH3), 1.52-1.49 (3H, dd, CH3ala). 13 C NMR: d 173.6 (CO), 150.1 ('ipso r lPh), 130.3 ("o'-Ph), 126.4 Cp'-Ph), 120.9 (" m'-Ph), 53.2 (OCH3), 50.9 ( CHala), 21.0 (CH3ala).

O- [Phenyl- (methoxy-D-alaninyl)] -phosphate of (SS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol. C24H3o05N7P? , PM = 527.53. This was synthesized according to Standard Procedure 4, using (ÍS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol (400 mg, 1.4 mmol), tBuMgCl (1.0 M solution in THF) (2.1 ml, 2.1 mmol), and phenyl (methoxy-D-alaninyl) phosphorochloridate (0.6 M solution in THF) (7.0 ml, 4.19 mmol) in THF (25 ml) stirring at room temperature for 36 h. The crude product was purified by eluting with 3% MeOH in CHCl and then 2.5% MeOH in CHC13 to give the product as a white foam (318.6 mg, 43.2%). 1P NMR: d 3.93, 3.70. NMR of XH: d 7.56 + 7.51 (1H, d, H8), 7.37 7.32 (2H, m, "o'-Ph), 7.29 (1H, d, 'p'-Ph), 7.25-7.15 (2H, m , 'jp'-Ph), 6.10 (1H, t, J = 5.28 Hz, H2'), 6.03 (1H, ¡bs, % NHcPr), 5.94-5.89 (1H, m, H3 '), 5.54 (1H, bs, Hl'), 5.01 (2H, bs, NH2), 4.26-3.83 (4H, m, CHala, NHala + H5 ' ), 3.72 (3H, d, OCH3), 3.18 (1H, s, CHcPr), 3.02 (1H, bs, H4 '), 2.86-2.75 (1H,, 1 of H6'), 1.78-1.64 (1H, m, 1 of H6 '), 1.39-1.36 (3H, dd, CH3ala), 0.90 -0.83 (2H, q, J = 6.13Hz, 2H of CH2cPr), 0.63 (2H, bs, 2H of CH2cPr) j NMR of 13C: d 174. '5 (CO), 160.3 (C2), 156.6 (C4) , 151.2 (C6), 151.0 ('ipso'-Ph), 136.8 (C2'), 136.1 (C8), 131.5 (C3 '), 130.0 (' m'-Ph), 125.3 Cp'-Ph), 12Q. 5 (O'-Ph), 115.2 (C5), 69.3 (C5 '), 59.3 (Cl'), 52.9 (CHala), 50.5 (OCH3), 46.0 (C4 '), 34.9 (C6'), 24.1 (CHcPr ), 21.4 (CH3ala), 7.8 (CH2cPr). MS ES +: m / z 527.86 (100%) (M) +, 546.84 (M +? J +, MS FAB: For C24H3? 05N7P requires 528.212431. found 528.211505. HPLC: tR 29.807 (100%) - (100% water ( 0 min), 20% water (35 min), 20% water (45 min), 100% water (55 min).) IR: 3333.6 (N-Hstr.), 2923.4, 2853.4 (C-Hstr. ), 1734.1 (C = Ostr.), 1591.1 (C aromatic Cstr.), 1458.3 (C-Hdef.), 1376.7 (-CH3sim. Def.), 1208.3 (PO-arila), 1153.3 (C-Ostr.), 1026.9 (PO-alkyl), 931.9 (C olefinic-Hdef.), 721.6 (monosubstituted aromatic C-Hdef).

(Methoxy-L-phenylalaninyl) -phenyl phosphorochloride C? 6H? 704N1Cl1P ?, MW = 353.74. This was synthesized according to Standard Procedure 3, using L-phenylalanine methyl ester (1.0 g, 4.64 mmol), PhOP (0) Cl2 (0.9 g, 0.70 ml, 4.64 mmol) and NEt3 (0.94 g, 1.30 ml, 9.28 mmol) yielding 1.45 g (88.4%) of crude product as an oil that was added to anhydrous THF (10 ml), yielding a 0.41 mmol / ml solution which was used without further purification. 31 P NMR: d 9.37, 9.23 (1: 1). 1 H NMR: d 7.60-7.16 (10H, m, 2xF), 4.70-4.49 (1H, m, CHala), 4.38-4.16 (1H, m, NHala), 3.89 (3H, d, OCH3), 3.23 (2H , m, CH2Ph).

O- [Phenyl- (methoxy-L-phenylalaninyl)] -phosphate from (1S, 4R * t-4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol Cf 1585. C3? H305N7P ?, PM = 603.6 This was synthesized according to Standard Procedure 4, using (ÍS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol (300 mg, 1.05 mmol), BuMgCl (1.0 M solution in THF) (1.57 mL, 1.57 mmol) and phenyl (methoxy-L-phenylalanyl) phosphorochloridate (0.41 M solution in THF) (7.66 mL, 3.14 mmol) in THF (20 mL) was stirred at room temperature for 48 h The crude product was purified by eluting with 3% MeOH in CHC13 and then 2.5% MeOH in CHCl3 to give the product as a white foam ( 272.9 mg, 43.15%), 31 P NMR: d 3.91, 3.80,? U-NMR: 7.47 + 7.43 (1H, d, H8), 7.31-7.06. (10H,, 2xF), 6.25 (1H, d, NHcPr), 6.00-5.95 (1H, q, H2 '), 5.87-5.81 (1H, t, H3'), 5.49 (1H, s, H1 '), 5,19 (2H, bs, NH2), 4.31-3.92 (4H, m, CHala, NHala + H5 ') - 3.64 (3H, d, OCH3), 3.02-2.89 (4H, m, CH2 Ph, CHcP + H4 '), 2.78-2.63 (1H, m, 1 H6'), 1.63-1.49 (1H, m, 1 H6 '), 0.86-0.80 (2H, q, J = 6.24Hz, 2H of CH2cPr), 0.60 (2H, d, 2H of CH2cPr). 13 C NMR: d 174.3 (CO), 161.5 (C2), 157.7 (C4), 152.4 (C6) 152.1 (* ipso '-OPh), 137.7 ("ipso'-Bn), 137.1 (C2f), 136.9 (C8), 132.4 (C3'), 130.9 (* or +" m'- Bn), 129.9 (? M '-OPh), 128.4 ("p'-Bn), 126.2 (p'-OPh), 121. 5 (o'-OPh), 116.1 (C5), 70.1: C5 '60.1 (CU), 57. 2 (CHala), 53.6 (OCH3), 46.9 (C6 '), 41.7 (C4'), 35.9 (CH2Ph), 25.1 (CHcPr), 8.7 (CH2cPr). MS ES +: m / z 603.8 (100%, M +), 604.8 (35%, M + H +), 625.7 (15%, M + Na +). MS FAB: For C31H34O5N7P requires 604.243731, found 604.242585.

HPLC: tR 34.707. 35.020 (100%) - (100% water (0 min), 20% water (35 min), 20% water (45 min), 100% water (55 mm)). IR: 3331.7 (N-Hstr.), 3007.2, 2952.2 (C-Hstr.), 1741.1 (C = Ostr.), 1595.6, 1487.7 (C aromaticCstr.), 1455.0 (C-Hdef.), 1393.9 (-CH3sim. def.), 1252.5 (P = 0), 1214.3 (P-0-aryl), 1125.3 (C-Ostr.), 1025.6 (PO-alkyl), 935.8 (C-olefinic-Hdef), 754.8 (monosubstituted aromatic C Hdef. ). (methoxiglicinyl) -phenyl phenylphosphorochloride CSHUOI ICIIPI, MW = 263.62. This was synthesized according to Standard Procedure 3, using glycine methyl ester (1.5 g, 11.9 mmol), PhOP (0) Cl2 (2.52 g, 1.79 mL, 11.9 mmol) and NEt3 (2.42 g, 3.33 mL, 23.9 mmol. ), providing 3.07 g (97.15%) of crude product as an oil which was stored with anhydrous THF (15 ml), yielding a solution of 0.774 mmol / ml which was used without further purification. 31P NMR: d 10.43. XH NMR: d 7.43- ?, 38 (2H, m, O'-Ph), [7.31-7.25 (3H, m, 'm' + 'p'-Ph), 4.67 (1H, bs, NHala), 3.94 (2H, dd, CH2), 3.83 (3H, s, OCH3).

«S ^^ 13C NMR: d 170.4 (COJ 150.1 ('ipso' -Ph), 130. 2 ('m'-Ph), 126.4 Cp'-Ph), 120 (O'-Ph), 53.1 (0CH3), 43.4 (CH2).

O- [phenyl- (methoxy-glycinyl)] -phosphate of (1S, 4R) -4t (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol. Cf 1588. C23H28? 5N7P? , PM = 513.49. This was synthesized according to | Standard Procedure 4, using (ÍS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol (300 mg, 1.05 mmol), tBuMgCl (solution 1.0 M in THF) (1.57 mL, 1.57 mmol) and phenyl (methoxiglicinyl) phosphorochlorurate (0.774 M solution in THF) (4.06 mL, 3.14 mmol) in THF (20 mL) was stirred at room temperature for 96 h. The crude product was purified by elution with 3% MeOH in CHC13 and then with 2.5% MeOH in CHC13, yielding the product as a white foam (82.6 mg, 15.4%). 31P NMR: d 4.79. 4.67 (1: 1). 1 H NMR: d 7.40 + 7.36 (1H, d, H8), 7.24-7.19 (2H, t, O'-Ph), 7.15-7.10 (2H, t, 'm'-Ph), 7.07 ^ 7.02 (1H, t, 'p'-Ph), 6.00-5.96 (2H, m, H2' + NHcPr), 5.80 | 5.76 (1H,, H3 '), 5.45-5.41 (1H, t, Hl'), 4.99 (2H, ¡bs, NH2), 4.14-4.00 (3H, m, NHala + H5 '), 3.62 (3H, s, OCH3), 3.03 (1H, d, H4'), 2.91 (1H, d, CHcPr), 2.73-2.62 (1H , m, 1 of H6 '), 1.62-1.51 (1H, m, 1 of H6'), 1.45-1.43 (6H, t, 2xCH3), 0.78-0.71 (2H, q, 2H of CH2cPr), 0.54- 0.49 (2H, t, 2H of CH2cPr).

Methyl-2-amino-2-methylpropanoate hydrochloride, C5H? 202NaCl ?, MW = 153.61.

This was synthesized according to the Standard procedure 1, using 2-ammo-isobutyric acid (4 g, 0.039 mol) with thionyl chloride (5.66 ml, 0.078 mol) and anhydrous methanol (23.5 ml, 0.58 mol). This gave the product as a white solid (5.805 g, 97.4%). XH NMR (DMSO): d 8.85 (3H, s, NH3 + C1 ') | 3.72 (3H, s, OMe), 1.48 (6H, s, 2xMe). NMR of 13C (DMSO): d 172.8 (COOMe), 56.6 (OMe) 53.9 (CMe2), 24.1 (2xMe). MS ES +: m / z 117.71 M + H +, 142.88 M + Na +.

(Methyl-2-amino-2-methylpropanoate) -phosphorochloridate of fe? Ilo. C? H? 504N1Cl? Px, MW = 291.67. This was synthesized according to Standard Procedure 3, using 2-amino-isobutyrate methyl ester hydrochloride (1.0 g, | 6.51 mmol), PhOP (0) Cl2 (1.37 g, 0.97 ml, 6.51 mmol) and NEt3 (1.32 g, 1.18"ml, 13.02 mmol), yielding 1.73 g (91%) of the crude product as an oil.This was stored with anhydrous THF (10 ml), providing a solution of 0.593 mmol / ml and used without purification Additional: 31P NMR: d 6.86.

XH NMR: d 7.43-7.38 (2H, t, O'-Ph), 7.32-7.21 (3H, m, 'm' + 'p'-Ph), 4.84 (1H, d, NHala), 3.83 (3H , s, OCH3), 1.72 (6H, d, 2xCH3). 13 C NMR: d 175.7 (CO), 150.3 ("ipso * ¡-Ph), 130.3 ('m'-Ph), 126.3 Cp'-Ph), 121.0 (O'-Ph), 58.8 (OCH3), 53.6 C [CH3] 2), 27.3 + 27.0 (2xCH3).

O- [Phenyl- (methoxy-a, a-dimethylglycinyl)] -phosphate (1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol. Cf 1584. C25H3205N7P? , PM = 542.23. This was synthesized according to Standard Procedure 4, using (ÍS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol (300 mg, 1.05 mmol), tBuMgCl (1.0 M solution in THF) (1.57 ml, 1.57 mmol) and phenyl (methoxy-dimethylglycinyl) -phosphorochloridate (0.59 M solution in THF) (5.3 ml, 3.14 mmol) in THF (20 ml) was stirred at room temperature for 96 hours. The crude product was purified by elution with 3% MeOH in CHC13 and then with 2.5% MeOH in CHC13, providing the product] as a white foam (193.7 mg, 34.14%). 31 P NMR: d 2r49. NMR of XH: d 7.40 + 7.36 (1H, d, H8), 7.24-7.19 (2H, t, O'-Ph), 7.15-7.10 (2H, t, 'm'-Ph), 7.07-7.02 (1H , t, * p * -Ph), 6.00-5.96 (2H, m, H2 '+ NHcPr), 5.80-5.76 (1H, m, H3'), 5.45-5.41 (1H, t, Hl '), 4.99 ( 2Hj bs, NH2), 4.14-4.00 (3H, m, NHala + H5 '), 3.62 (3H, s, 0CH3), 3. 03 (1H, d, H4 '), 2.91 (1H, d, CHcPr), 2.73-2.621 (1H, m, 1 of H6'), 1.62-1.51 (1H, m, 1 of H6 '), 1.45J- 1.43 (6H, t, 2xCH3), 0.78-0.71 (2H, q, 2H of CH2cPr), 0.54- 0.49 (2H, t, 2H of CH2cicl.). MS ES +: m / z 541.9 (100%, M +), 563.8 (30%, M + Na +). MS FAB: For C25H33? 5N7P requires 542.22) 8081, found 542.228428. HPLC: tR 28.347 (100%) - (100% water (0 ml?), 20% water (35 min.), 20% water (45 min.), 100% water (55 min.)). IR: 3346.0 (N-Hstr.), 2923.0, 2853.5 (C-Hstr.), 1734. 0 (C = Ostr.), 1590.2 (C aromatic Cstr.), 1458.4 (C-Hdef.), 1376.8 (-CH3sim. Def.), 1261.3 (P = 0), 1152.7 (C-Ostr.), 1028.0 ( PO-alkyl), 936.0 (C-olefinic-Hdef.), 721.7 (monosubstituted aromatic C-Hdef.).

L-aspartic acid dimethyl ester hydrochloride. C6H1204N? Cl1, MW = 197.62. This was synthesized according to the Normalized Procedure 1, using L-asparagine (2 J 5 g, 0.019 mol) with thionyl chloride (3.67 ml, 0.042 mol) and anhydrous methanol (12.86 ml, 0.32 mol). This provided the hydrochloride of the L-aspartic acid dimethyl ester in a yield of 99%, 3.70 g. NMR of? H (MeOH-d4): d 4.53-4.50 (1H, t, | CH), 3.94 (3H, s, OCH3), 3.85 (3H, s, 0CH3), 3.18 (2H, d, CH2) • 13 C NMR (MeOH-d 4): d 170.4-168.4 '(CO), 53.0 + 52.0 (2xOMe), 49.4 (CH), 33.8 (CH2).

(Dimetoli-L-aspartyl) phenylphosphorochloride. C? 2H? 506N? Cl? P ?, MW = 335.68. This was synthesized according to 'Standard Procedure 3, using dimethyl aspartic acid ester (1.0 g, 5.04 mmol), PhOP (0) Cl2 (1.06 g, 0.75 ml, 5.04 mmol) and NEt3 (1.02 g, 1.40 ml, 10.1 mmol) yielding 0.55 g (32.4%) of crude product as an oil that was stored with anhydrous THF (5 ml), yielding a solution of 0.33 mmol / ml which was used without further purification. 31 P NMR: d 9.74, 9.59 (1: 1).

O- [phenyl- (L-aspartic acid dimethyl ester)] - (1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol phosphate. C24H3o05N7P1, MW = 527.53.

This was synthesized according to the Standard procedure 4, using (lS, 4R) -4- (2-a < mmo-6-c? Clopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol (250 mg, 0.87 mol) , tBuMgCl (1.0 M solution in THF) (0.87 ml, 0.87 mmol) and (L-aspartic acid dimethyl ester) phenylphosphorochloride (0.50 M solution in THF) (5.20 ml, 2.62 mmol) in THF (15 ml) and stirring at room temperature for 48 h. The crude product was purified by elution with 2.5% MeOH in CHCl2 (x2) affording the product as a pale yellow foam (163.5 mg, 32.0%). 31P NMR: d 4.19, 3.76 (1: 1). XH NMR: 7.40 (1H, d, H8), 7.24-7.19 (2H, t, O'-Ph), 7.12-7.03 (3H,, 'm' + 'p'-Ph), 6.05-5, 95 (2H, m, H2 '+ NHcPr), 5.79 (1H, d, H3'), 5.44 CH, s, H1 '), 5.02 (2H, bs, NH2), 4.38-4.07 (4H, m, H5 ', NHala + CHala), 3.61 (3H, s, OCH3), 3.54 (3H, d, OCH3), 3.05-2.52 (5H, m, CH2aa, H4', CHcPr, + 1 of H6 '), I 1.6 , 4-1.52 (1H, m, 1 of H6 '), 0.77-0.73 (2H, t, J = 5.49 Hz, 2H of CH2cPr), 0.51 (2H, bs, 2H of CH2cPr). NMR of 1 ± 3J, C: d 173.3 (CO), 172.4 (CO), 161.5 (C2), 157.7 (C4), 152.3 (C8), 152.1 ('ipso' -Ph), 137.8 (C2 '), 137.0 (C6), 132.6 (C3 '), 131.1 (' m * -Ph), 126.4 Cp'-Ph), 121.6 (O'-Ph), 116.2 (C5), 70.5 (C5 ') 6Q.3 (Cl '), 54.3 (OCH3), 53.5 (OCH3), 52.6 (CHala), 1 47.1 • fejt ^? fc ^ (C4 '), 39.7 (CH2ala), 36.0 (C6'), 25.1 (CHcPr), 8.8 (CH2cPr). MS ES +: m / z 585.8 (100%, M +), 607.7 (30%, M + Na +). MS FAB: For C26H33? 5N7P requires 586.2l | 7910, found 586.217510. HPLC: tR 29.261 (100%) - (100% water (0 min), 20% water (35 min), 20% water (45 min), 100% water (55 ml?). IR: 3347.5 (N-Hstr.), 2850.7 (C-Hstr.), H739.9 (C = Ostr.), 1596.1 (C aromatic-Cstr.), 1461.9 (C-Hdef.), 1376.6 (-CH3sim. def.), 1262.4 (P = 0), 1211.2 (PO-arylc?), 1158.3 (C-Ostr.), 1027.0 (PO-alkyl), 935.6 (C-olefinic-Hdef.), 761.5, 722.0 (monosubstituted aromatic C -Hdef.). 3-cyclohexyl-L-alanine methyl ester hydrochloride salt. This was synthesized according to 'Standard Procedure 1, using 3-cyclohexyl-L-alanine (3.0 g, 17.5 mmol), methanol (30 ml), and thionyl chloride (2.56 ml, 35 mmol). The product was isolated as a white solid (3.23 g, 83.9%).

NMR of XH (MeOH-d4): d 4.12-4.07 (3H, t, CHala), 3.85 (3H, s, OCH3), 1.74-1.68 (6H, m, CH2 +? - CH2), 1.56-1.43 (1H ,, CH), 1.36-1.15 (4H, m, m-CH2), 1.05¡-Q.90 (2H, q, p-CH2). 13 C NMR: 170.15 (CO), 52.7 (OCH3), '50.8 (CHala), 38.2 (CH2), 33.6 (CH), 33.0 + 32.7 (2xCH2-o), 26.3 (p-CH2), 26.0 + 25.9 (2xCH2-m).

(Methoxy-3-cyclohexyl-L-alaninyl) -phosphorochloride phenyl C? 6H23N? 04P? Cl ?, MW = 359.82 This was synthesized according to the Normalized procedure 3, using hydrochloride salt of the methyl ester of 3-cyclohexyl-L-alanine (0.7 g, 316 mmol), PhOP (0) Cl2 (0.47 ml, 3.16 mmol), triethylamine 1 (0.88 ml, 6.31 mmol) in DCM (60 ml). The usual treatment gives the crude product as a yellow oil (1.18 g, 100%), which is stored with THF (7 ml) providing a 0.45M solution. 31 P NMR: d 9.79, 9.49 (1: 1). 2H NMR: d 7.49-7.43 (2H, m, O'-Ph), 7.37-7.19 (3H,, 'm' + 'p'-Ph), 4.46-4.35 (1H, q, NHala), 4.32- 4.20 (1H, m, CHala), 3.88-3.85 (3H, dd, OCH3), 1.94-1.90 (1H, d, CHcHx), 1.76-1.60.

-A.JM »». - * >; - -O-Phenyl- (methoxy-3-cyclohexane-L-alaninyl) -phosphate (1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopenteno- 1-methanol. Cf 1709. C30H40N7O5P? , MW = 609.66 This was synthesized according to Standard Procedure 4, using (ÍS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol ( 150 mg, 0.52 mmol), tBuMgCl (1.05 ml, 1.05 mmol, of a 1.0 M solution in THF), in THF (4 ml) and (methoxy-3-cyclohexane-L-alaninyl) phenylphosphorochloride (3.5 ml, 1.57 mmol, of a 0.45 M solution in THF), at room temperature for 24 h. After 24 h, additional phenyl (methoxy-3-cyclohexane-L-alaninyl) -phosphorochloridate (2.5 ml, 1.12 mmol, of a 0.45 M solution in THF) was added and the reaction was stirred for a further 24 h. The crude product was purified by elution with 3% MeOH in CHC13, and then 2.5% MeOH in CHC13, providing the pure product as a pale yellow solid (79.6 mg, 24.9%). 31P NMR: d 4.14, 3.98 (1: 1). 1E NMR: 7.50 (1H, d, H8), 7.34-7.13 (5H, t, OPh), 6.20 (1H, s, NHcPr), 6.08 (1H, t, H2 '), 5.89 (1H, q, H3 '), 5.53 (1H, bs, H1'), 5.16 (2H, bs, NH2), 4. 24-3.84 (4H, m, H5 ', NHala + CHala), 3.66 (3H, s, OCH3) 3. 34 (1H, bs | 3.11 (1H, d) 3.03 (1H, bs 2.84 1-2.72 (1H, m, 1 of H6 '), 1.98-1.36 (8H, m,), 1.11 (3H, bs), 0.89 -0.83 (4H, m, 2H of cPr + CH2- 'p'), 0.63 (2H, d, 2H of cPr). 13 C NMR: 174.8 CO 160.2 (C2), 156.5 (C4), 151.3 (C6). , 151.2 (* ipso'-Ph), 136.8 (C2 '), 135.9 (C8), m, -' (('< ñ' '-) p, h) 52.JJdHi?) 46. 1 (C4 '), 42.5 (CH2), 34.9 (C6'), 33.8 (CHcHx)!, 3? .7 (CH2-'o '), 26.7 (CH2-m'), 26.4 (CH2-'p *), 24.2 (CHcPr), 7.8 (CH2cPr). MS ES +: m / z 610.3 (40%, M +), 632.3 (100%, M + Na +), 633.3 (25%, M + H + Na +). MS FAB: For C3oH4o05N7NaP it requires 632.2726, found 632.2727. HPLC: tR 42.154 (100%) - (100% water (O1 min) / 20% water (35 min), 20% water (45 min), 100% water (55 min)).

Diammonium salt of (1S, 4R) -4-t (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol (L-alaninyl) -phosphate. Cf lf40. O- [Phenyl- (methoxy-L-alaninyl)] -phosphate of (SS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-l9-yl) -2-cyclopentene-l- was stirred. methanol (125 mg, 0.24 mmol) in H2JO: NE "J3 (10 mL, 1: 1 v / v), at 25-35 ° C for 5 hours.The reaction mixture was extracted with DMC (8-20 mL) and the aqueous layer was reduced to dryness The resulting solid was solubilized in isopropanol and purified by flash column chromatography, eluting cpn a gradient of i-PrOH: H20: NH3 (11: 1: 1 to 9: 1: 2) The appropriate fractions were reduced to dryness and lyophilized to yield the pure product as a white foamy solid (106 mg, 95%) 3 311P NMR (D20): -d 8.62 (s) .XE NMR (D20) : - d 7.79 (1H, s, H8), 6.08 (1H, d, H2 '), 5.77 (1H, d, H3'), 5.35 (1H, t, Hl '), 3.7ll-3, 58 (2H,, H5 '), 3.41-3.32 (1H, m, CHa.a), 3.02-2.94J (1H,, NHCH), 2.70-2.59 (2H, m, H4' + l of CH2), 1.57 | -1.49 (1H, dt, 1 of CH2), 1.10 (3H, d, CH3), 0.83-0.76 (2H, q, 1 of CH2cycle.), 0.61-0.56 (2H, q, 1 of CH2cycle.). MS ES +: m / z 437.9 (100%, M +). MS FAB: calculated m / z 438.165481, found m / z 438.163790.

Diammonium salt of (1S, 4R) -4t (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol O- (D-alanynyl) -phosphate O- [ phenyl- (methoxy-D-alaninyl)] -phospha, of (SS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentenyl-methanol (100 mg, 0.19 mmol) in H20: NEt3 (8 ml, 1: 1 v / v), for 16 hours. The reaction mixture was extracted with DCM (5 x 20 ml) and the aqueous layer was reduced to dryness. The resulting solid was solubilized in isopropanol and purified by flash column chromatography, eluting with gradient of i-PrOH: H20: NH3 (11: 1: 1 to 9: 1: 2). The appropriate fractions were reduced to dryness and lyophilized to give the pure product as a white foamy solid (88%). 31 P NMR (MeOH-d4): -d 7.81 (s). 1H-NMR: -d 7.74 (1H, s, H8), 6.12 (1H, d, J = 5.53Hz, H2 '), 5.78 (1H, t, H3'), 5.44 (1H |, d, J = 6.21 Hz, Hl '), 3.74 (2H, t, J = 5.42Hz, H5'), 3.70-3.60 (1H, m, CHala), 3.01 (1H, bs, H4 '), 2.84 (1H, d, J = 3.28Hz, CHcPr), 2.73-2.63 (1H, dt, 1 of H6 '), 1.67-1.58 (1H, m, 1 of C d, J = 7.01 Hz, CH3ala), 0.79-0.73 (2H, q , J = 6.68Hz, 2H of CH2cPr), 0.53 (2H, t, 2H of CH2cPr). 13 C NMR: d 179.8 (CO), 161.2 (C2), 157.1 (C4), 151.1 (C6), 139.5 (C2 '), 137.8 (C8), 130.7 (C3'), 114.6 (C5), 68.0 (C5 '), 60.5 (Cl'), 51.9 (CHala), 47.6 (C4 '), 35.9 (C6'), 24.4 (CHcPr), 21.7 (CH3ala), 7.6 (CH2sPr). MS ES +: m / z 437.9 (100%, M +). y ¿^ ^ MS FAB: calculated m / z 438.165481, found m / z 438.167842.

(Ethoxy-L-alaninyl) -phenyl phosphorochlorurate. This was synthesized according to Standard Procedure 3, using L-alanine ethyl ester hydrochloride (1.0 g, 6.51 mmol), PhOP (0) Cl2 (1.37 g, 0.97 ml, 6.51 mmol) and NEt3 (1.32 g, 1.81 ml, 13.0 mmol), providing 1.85 g (97.4%) of crude product as an oil which was stored with anhydrous THF (10 ml), yielding a solution of p.63 mmol / l which was used without further purification.; d 9.41. 9.16 (1: 1). 1H NMR: d 7.42-7.35 (2H, dd, O'-Ph), 7.31- 7.25 (3H, m, 'm' + 'p'-Ph), 4.71 (1H, d, NHala), 4.31-4 , 13 (3H,, OCH2 + CHala), 1.55-1.52 (3H, dd, 0CH2CH3), 1.33-1.30 (3H, dd, CH3ala). 13 C NMR: d 173.1 (CO), 150.2 ('ipso' -Ph), 130.3 ("m'-Ph), 126.4 (" p'-Ph), 120.9 (O'-Ph), 62.3 (OCH2), 51.0 (CHala), 20.9 (CH2CH3), 14.5 (CH3ala).

O- [Phenyl- (ethoxy-L-alaninyl)] -phosphate of (SS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol . Cf 1587.

, TO. r C? 2H3o05N7P ?, MW = 527.53. This was synthesized according to Standard Procedure 4, using (ÍS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol (300 mg, 1.4 mmol), tBuMgCl (1.0 M solution in THF) (1.57 mL, 1.57 mmol), and phenyl (ethoxy- ^ L-alaninyl) phosphorochloridate (0.49 M solution in THF) (6.45 mL, 3.14 mmol) in anhydrous THF (20 mL). ml), and stirring at room temperature for 24 hoursl. The crude product was purified by column chromatography eluting with 2.5% MeOH in CHC13, affording the product as a pale yellow foam (2910 mg, 51.1%). 31 P NMR: d 4.04, 3.96 (1: 1). XH NMR: d 7.39 (1H, d, J = 7.56Hz, H8), 7.23- 7.18 (2H, t, J = 7.90Hz, O'-Ph), 7.12-7.10 (2H, t, 'm' Ph ), 7.06-7.01 (1H, t, J = 7.13Hz, 'p'-Ph), 6.18 (1H, bs, NHcPr), 5.97-5.95 (1H, t, H2'), 5.79-5.75 (1H, t , J = 5.55Hz, H3 '), 5.43 (1H, s, Hl'), 5.13 (2H, bs, I NH2), 4.30-4.14 (1H, m, NHala), 4.06-4.00 (4H, m, H5 '+ ¡OCH, 2), 3. 96-3.84 (1H, m, CHala), 3.03 (1H, d, J = 5.74Hz, H4 '), 2.92 (1H, bs, CHcPr), 2.71-2.61 (1H, m, 1 of H6'), ! 1.60-1.51 (1H, m, 1 of H6 '), 1.29-1.24 (3H, t, J = 6¡.64Hz, CH3ala), 1.18-1.11 (3H, m, CH2CH3), 0.75-0.71 (2 H, q, J = 6.76Hz, 2H of CH2cPr), 0.50 (2H, bs, 2H of CH2cPr) J NMR of d 173.35 (CO), 159.8 (C2), 156.0 (C4), 150.6 (C6) 150.4 (* ipso'-Ph), 136.1 (C2 '), 135.1 (C8), 130.8 (C3'), 129.3 ('m'-Ph), 124.5 (' p '-Ph), I 119.8 (O'-Ph) 114.4 (C5) 68.6: c5 '61.2 (OCH2) ,? 58.5 (Cl '), 50.0 (CHala), 45.3 (C4'), 34.3 (C6 '), 33. (CHcPr), 20.6 (CH3ala), 13.8 (CH2CH3), 7.0 (CH2CPr). MS ES +: m / z 541.9 (100%, M +), 546.84 (28%, M + H +), 563.8 (25%, M + Na +). MS FAB: For C25H33O5N5P, it requires 542.228081, found 542.228131. HPLC: t R 31.76, 32.03 (100%) - (100% water (0 min), 20% water (35 min), 20% water (45 min), 100% water (55 ml?) .

IR: 3334.1 (N-Hstr.), 1734.5 (C = Ostr.), 1595.9, 1488. 0 (C aromatic-Cstr.), 1450.3 (C-Hdefl.), 1394.2 (-CH3sim.def.), 1252.8 (P = 0), 1210.4 (P-O-aryl), 1153.3 (C-Ostr.), 1026.0 (P-O-alkyl), 934.8 (C-olefinic-Hdef.), 759.0 (monosubstituted aromatic C-Hdef.).

(Benzoxy-L-alaninyl.) Phenyl phosphorochloridate This was synthesized according to Standard Procedure 3, using L-alanine benzyl ester hydrochloride (1.0 g, 4.64 mmol), PhOP (0) Cl2 (0.98 g, 0.69 ml, 4.64 mmol) and Net3 (0.94 g, 1.29 ml, 9.27 mmol), providing 1.61 g (98.2%) of crude product which was stored with anhydrous THF (10 ml), providing a 0.46 mmol / ml solution used or without further purification .. 31 P NMR: d 9.41, 9.23 (1: 1) XH NMR: d 7.41-7.21 (10H, m, 2xPh), 5.24 (2H, d, CH2Ph), 4.95-4.88 ( 1H, t, NHala), 4.36-4.15¡ (1H, m, CHala), 1.56 (3H, t, CH3ala), 13C NMR: 172.9 (CO), 150.2 ('ipso' OPh), 135.5 ('ipso '-CH2Ph), 130.3 (' m'-OPh), 129.0 (O'-CH2Ph), 128.7 ('m' + 'p'-CH2Ph), 126.4 (? P'-OPh), 121.0 (O'-OPh ), 68.0 (OCH2), 51.1 (CHala), 20.8 (CH3ala).

O- [Phenyl- (benzoxy-L-alaninyl)] -phosphate of (SS, 4R) -4 (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol. Cf1582 t C3oH35? 5N7P? , PM = 603.6. This was synthesized according to Standard Procedure 4, using (ÍS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol (400 mg, 1.4 mmol), tBuMgCl (1.0 M solution in THF) (2.1 ml, 2.1 mmol), and phenyl (benzoxy-L-alanyl) -phosphorochloridate (0.46 M solution in THF) (9.2 ml, 4.19 mmol) in anhydrous THF (20 ml), and stirring at room temperature for 64 h. The crude product was purified by column chromatography eluting with 3% MeOH in CHC13, and then with 2.5% MeOH in CHC13, affording the product as a white foam (82.2 mg, 9.75%). A second synthesis was performed with (lS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol (200 mg, 0.7 mmol), tBuMgCl (2.43 ml of a 1.0 M solution in THF, 2.43 mmol) and phenyl (benzoxy-L-alaninyl) -phosphorochloridate (2.2 ml of 0.46 M solution in THF, 2.1 mmol) in THF (2.5 ml). Purification by column chromatography eluting with 3% MeOH in CHC13 afforded the pure product as a white foamy solid (90 mg, 21.3%). 31 P NMR: d 3.82, 3.72 (1: 1). 1 H NMR: d 7.51 (1H, d, H8), 7.37-7.15 (10H, m, 0Ph + CH2Ph), 6.10-6.04 (1H, m, H2 '), 5.96 (1H, bs, NHcPr), 5.89 ( 1H, dd, J = 5.36Hz, H3 '), 5.54 (1H, t, Hl *), 5.16 (2H, bs, NH2), 4.96 (2H, bs, CH2Ph), 4.23-4.05 (3H,, NHala + H5 '), 3.89-3.70 (1H, dt, CHala), 3.16-3.12 (1H, t, H4'), 3.03 (1H, bs, CHcPr), 2.85-2.71 (1H, m, ¡1 of H6 ') , 1.74-1.64 (1H, m, 1 of H6 '), 1.44-1.39 (3H, t, 1 = 7.84 Hz, CH3ala), 0.88 (2H, q, J = 6.75Hz, 2H of CH2cPr), 0.64 (2H , m, 2H of CH2cPr).

NMR of 13 C: d 173.3 (CO) 159.7 (C2) 156.0 (C4), 150.9 (C6), 150.7 ('ipso' -OPh), 136.4 (C2 '), | 135.7 (* ipso'-Bn), 135.2 (C8), 131.0 (C3 '), 129.6 (' c'-Bn), 128. 6 Cm'-Bn), 128.5 (* p'-Bn), 128.2 ('m'-OPh), 124.9 Cp'-OPh), 120.1 (O'-OPh), 114.8 (C5), 68.8 (C5') ), 67.2 (CH2Ph), 58.9 (Cl '), 50.3 (CHala), 45.6 (C4'), 34.4 (C6 '), 23.7 (CHcPr), 21.0 (CH3ala), 7.4 (CH2cPr). MS ES +: m / z 603.8 (100%, M +), 604.8 (30%, M + H +), 625. 7 (20%, M + Na +). MS FAB: For C30H35O5N7P requires 604.2) 43731, found 604.241775. HPLC: tR 33.39 (99.7%) - (100% water (0 min), 20% water (35 min), 20% water (45 min), 100% t water (55 min)). IR: 3355.9 (N-Hstr.), 2923.3, 2853.7 (C-Hstr.), 1734. 1 (C = Ostr.), 1595.6 (C aromatic-Cstr.), 1458.4 (C-Hdef.), 1376.5 (-CH3sim. Def.), 1154.4 (C-Ostr.), 1028.2 (P-O-alkyl), 935.8 (C-olefinic-Hdef.), 721 i 7 (monosubstituted aromatic C-Hdef.).

N-propyl ester hydrochloride salt of L-alanine C6H? 4N? 02Cl ?, PM = 167T634 This was synthesized according to Standard Procedure 1, using anhydrous propane-1-ol (42.0 ml, 0.56 mol), thionyl chloride (8.2 ml, 0.112 mol) and L-alanine (5.0 g, 0.056 mol). The product was isolated as a white solid (8.88 g, 94.3%). NMR of XH (MeOH-d): d 4.34-4.26 (2H, m, OCH 21 i 4.24-4.17 (1H, q, CHala), 1.88-1.78 (2H, m, CH2), 1.65 (3H, d, J = 7.24Hz, CH3ala), 1.10-1.05 (3Hf t, CH2CH3) 13 C NMR: 170.1 (CO), 68.0 (OCH2), 48.9 (CHala), 21.9 (CH2), 15.3 (CH3ala), 9.5 (CH2CH3) . (n-propoxy-L-alaninyl) -phosphorochloride phenyl C12H? 7N? 04P? Cla, MW = 30 $ .79 This was synthesized according to Standard Procedure 3, using the hydrochloride salt of the n-propyl ester of L- alanine (0.5 g, 2.98 mmol), PhOP (0) Cl2 (0.45 mL, 2.98 mmol), triethylamine (0.83 mL, 5.97 mmol) in DCM (70 mL). The usual treatment gave the crude product as a yellow oil (0.84 g, 92.1%), which was stored with THF (5 ml), providing a 0.55M solution. 31 P NMR: d 9.41, 9.17 (1: 1). NMR of 13, d 173.1 (CO), - 150.1 ('ipso' -Ph) 130. 0 ('m'-Ph), 126.4 (' p'-Ph) 121.0 (O'-Ph; 67.9 (OCH2), 51.0 (CHala), 22.3 (CH2CH3), 21.0 (CH3ala), 10.7 (CH2CH3).

O-Phenyl- (n-propoxy-L-alaninyl) -phosphate of (1S, 4R) -4t- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cislopentene-1-methanol. C26H34N705P ?, MW = 555.57 This was synthesized according to Standard Procedure 4, using (1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1 methanol (100 mg, 0.35 mmol), tBuMgCl (0.7 mL, 0.7 mmol, of a 1.0M solution in THF), in THF (3 mL) and (p-n-propyl-L-alaninyl) -phosphorochloridate (1.9 mL, 1. 05 mmol, from a 0.55M solution in THF), at room temperature for 24 h. The crude product was purified by elution with 3% MeOH in CHC13, affording the pure product as a pale yellow foamy solid (123 mg, 63.4%). NMR of 31, d 4.06, 3.98 (1: 1) 1E-NMR: 7.40 (1H, d, J = 7.99Hz, H8), 7.23-7.18 (2H, dd, O'-Ph), 7.12-7.02 ( 3H, m, 'm' + 'p'-Ph), 6.16 (1H, bs, H3'), 5.96 (1H, t, H2 '), 5.78 (1H, d, J = 5.83Hz, NHcicl), 5.44 (1H, bs, Hl '), 5.15 (2H, ¡bs, NH2), 4.33-4.18 (1H, m, CHala), 4.15-4.04 (2H, m,?' CH2), 4. 01-3.88 (2H, m, H5 '), 3.65 (1H, bs, NHala), 3.03 (1H, d, H4'), 2.92 (1H, bs, CHcicl), 2.72-2.62 (1H, m, 1 H6 '), 1.60-1.47 (3H, m, 1 of H6' + CH2CH3), 1.30-1.26 (3H, t, CH3ala), 0.84-0.80 (3H, • m, CH2CH3), 0.73 (2H, d, J = 6.8Hz, 1 of CH2cicl), 0.51 (2H, bs, 1 of CH2cicl) NMR of 13 d 174. ICO 160.4 (C2), 156.6 I (C4 | 151. 1 (C6 + 'ipso' -Ph), 136.8 (C2 '), 135.9 (C8), i 131.5 (C3'), 130.0 Cm'-Ph), 125.2 Cp'-Ph), 120.5 (O] -Ph), 115. 0 (C5), 69.2 (C5 '), 67.4 (OCH2), 59.2 (Cl'), 50.6 (CHala), 46.0 (C4 '), 35.0 (C6'), 24.2 (CHcPr), 22.3 (CH2CH3), 21.5 (CH 3ala), 10.7 (CH 2 CH 3), 7.7 (CH 2 cyclo). MS ES +: m / z 555.8 (100%, M +), 557.0 (30%, M + H +). MS FAB: For C26H35O5N-7P it requires 556.¡2437, found 556.2438. HPLC: tR 34.708 (100%) - (100% water (0 min), 20% water (35 min), 20% water (45 min), 100% water (55 min)) • N-butyl ester hydrochloride salt of L-alanfna. C7H? 6N? 02Cl ?, MW = 181.661 This was synthesized according to Standard Procedure 1, using anhydrous butan-1-ol (51.4 ml, 0.56 mol), thionyl chloride (8.2 ml, 0.112 mol) and L-alanine (5.0 g, 0.056 mol). The product was isolated as a white solid (8.86 g, 86.9%). 2 H NMR: (MeOH-d4): d 4.29-4.17 (2H, m, OCH2), 4.13-4.06 (1H, q, CHala), 1.71-1.62 (2H, m, OCH2CH2), 1.53 (3H, d, J = 7.25Hz, CH3ala), 1.47-1.34 (2H, m, CH2CH3), 0.96-0.91 (3H, t, CH2CH3). 13 C NMR: 170.1 (CO), 66.2 (OCH2), 48.9 (CHala), 30.6 (OCH2CH2), 19.0 (CH2CH3), 15.3 (CHβala), 13. 0 (CH2CH3). (n-Butoxy-L-alaninyl) -phosphochloridate of fepilo C? 3H? 9N? 0P? Cl ?, MW = 317.82 This was synthesized according to Standard Procedure 3, using the hydrochloride salt of the n-butyl ester of L- alanine (0.5 g, 2.75 mmol), PhOP (0) Cl2 (0.41 ml, 2.75 mmol), triethylamine (0.7/7 ml, 5.5 mmol) in DCM (80 ml). The usual treatment gave the crude product as a yellow oil (0.84 g, 94.5%) which was stored with THF (5 ml), providing a 0.525M solution. 31 P NMR: d 9.39, 9.10 (1: 1). NMR of XH: d 7.43-7.15 (5H, m, Ph), 4.6 ^ -4.59 (1H, q, CHala), 4.27-4.05 (3H,, OCH2 + NHala), 1.73-1.59 (2H, m, OCH2CH2) , 1.56-1.53 (2H, dd, CH2CH3), 1.46-1.37 (3H,, CH3ala), 1.00-0.92 (3H, m, CH2CH3). 13 C NMR: d 173.2 (CO), 150.1 ('ipso' -Ph), 130.3 (* m'-Ph), 126.4 (* p'-Ph), 121.0 (o'-Ph), 66.2 (OCH2), 51.0 (CHala), 30.9 (OCH2CH2), 21.0 (CH3ala), 19.4 (CH2CH3), 14.1 (CH2CH3).

O-Phenyl- (n-butoxy-L-alaninyl) -phosphate of (1S, 4R) -4 (2-a-ino-6-cyclopropylamino-9H-purin-9-yl) -2-skypentene-1-methanol. Cf1647 C27H36N705P? , MW = 569,597 This was synthesized according to Standard Procedure 4, using (ÍS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol ( 100 mg, 0.35 mmol), tBuMgCl (0.7 ml, 0.7 mmol, of a 1.0M solution in THF), in THF (3 ml) and (p-n-butyl-L-alaninyl) phenylphosphorochloride (2.0 ml, i 1 , 05 mmol, of a 0.525M solution in THF), at room temperature for 24 h. The crude product was purified by elution with 3% MeOH in CHCl3 to give the pure product as a pale yellow foamy solid (157 mg, 78.9%). 1P NMR: d 4.01, 3.95 (1: 1). NMR from H: d 7.40 (1H, d, J = 7.32 Hz, H8), 7.23-7.18 (2H, t, O'-Ph), 7.11 (2H, t,? M '-Ph), 7.04 (1H, t, • p'-Ph), 6.02 (1H, bs, H3 '), 5.97 (1H, t, H2'), 5.78 (1H, bs, NHcicl), 5.44 (1H, bs, Hl '), 5.06 ( 2H, bs, NH2), 4.22-3.88 (6H, m, Chala, OCH2, H5 '+ NHala), 3.05 (1H, d, H4'), 2.93 (1H, bs, CHcicl), 2.72-2.62 (1H, m, 1 of H6 '), 1.61-1.47 (3H, m, 1 of H6' + OCH2CH2), 1.30-1.26 (5H, t, CH3ala + CH2CH3), 0.85-0.80 (3H, t, CH2CH3) 0.74 (2H, d, J = 6.45Hz, 1 of CH2cicl), 0.51 (2H, bs, 1 of CH2cicl). NMR of 13H: d 174.1 (CO), 160.4 (C2), 156.7 (C4), 151.2 (C6), 151.1 ('ipso'-Ph), 136.7 (C2'), ¡135.8 (C8), 131.5 (C3 '), 130.0 (* m'-Ph), 125.2 (p'-Ph), 120.5 (O'-Ph), 115.0 (C5), 69.3 (C5 '), 65.8 (0CH2), | 59.2 : ci '50.6' CHala! 46.0 (C4 ') 35.0 (C6') 30.9 (OCH2CH2), 24.1 (CHcPr), 21.5 (CH3ala), 19.4 (CH CH3), 141. 1 (CH2CH3), 7.8 (CH2cicl). MS ES +: m / z 569.9 (70%, M +), 570.9 (20%, M + H +), 591. 8 (100%, M + Na +), 607.8 (20%, M + K +). HPLC: tR 38.27 (100%) - (100% water (0 min), 20% water (35 min), 20% water (45 min), 100% water (55 ml?).

L-alanj.na i-propyl ester hydrochloride salt. C6H1N1O2CI1, MW = 167.634 This was synthesized according to the Standard procedure 1, using anhydrous propan-2-ol (43.0 ml, 0.56 mol), thionyl chloride (8.2 ml, 0.112 mol) and L-alanine (5.0 g, 0.056 mol). The product was isolated as a semi-crystalline solid (8.86 g, 86.9). NMR of? E (MeOH-d4): d 5.16-5.08 (1H, m, CH ^ la), 4.11-4.04 (1H, q, OCH (Me) 2), 1.55 (3H, d, J = 7). 21Hz CH3ala), 1.34-1.31 (6H, dd, CH (Me) 2). 13 C NMR: d 169.5 (CO), 7O.8 (COCH (Me) 2), 48.9 (CHala), 20.8 (CH3ala), 15.3 (CH (Me) 2). (i-Propoxy-L-alaninyl) -phenyl phenylphosphorochloride C? 2H17N? 04P? Cl ?, MW = 305.79 This was synthesized according to Standard Procedure 3, using hydrochloride salt of the L-alanine i-propyl ester (0.5 g, 2.98 mmol), PhOP (0) Cl2 (0.45 mL, 2.98 mmol), triethylamine (0.8: 3 mL, . 97 mmol) in DCM (70 ml) The usual work up gave the product as a yellow oil (12 g,> 100%), which was stored with THF (5 ml) providing a 0.597 M solution. 31P NMR: d 9.45, 9.17 (1: 1). 13 C NMR: d 172.6 (CO), 150.2 ('ipso' -Ph), 130.3 (m'-Ph), 126.4 (Xp'-Ph), 121.0 (O'-Ph), 70.1 (OCH), 51.1 ( CHala), 22.1 (CH (CH3) 2), 20.9 (CH3ala).

O-Phenyl- (i-propoxy-L-alaninyl) -phosphate of (SS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol. Cfl661. C26H34N705P? , MW = 555.57 This was synthesized according to Standard Procedure 4, using (ÍS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol ( 100 mg, 0.35 mmol), tBuMgCl (0.7 mL, 0.7 mmol, from a 1. OM solution in THF), in THF (3 mL) and (i-propyl-L-alaninyl) -phosphorochlorurate phenyl (1.76 ml, 1.05 mmol, from a 0.597M solution in THF), at room temperature for 72 h. The crude product was purified by elution with 3% MeOH in CHC13 (x2) to afford the pure product as a pale yellow foamy solid (106.8 mg, 54.8%). 31P NMR: d 4.02. 3.98 (1: 1). XH NMR: d 7.41 (1H, d, J = 8.12 Hz, H8), 7.24-7.19 (2H, m, O'-Ph), 7.13 -7.03 (3H, m, m '+' p'-) Ph), 6. 37 (1H, bs, NHcPr), 5.98 (1H, t, H3 '), 5.80-5.76 (1H, m, H2'), 5.43 (1H, bs, H1 '), 5.21 (2H, bs, NH2), -4.94-4.86 (1H, m, OCH), 4.15-3.98 (2H, m, H5 '), 3.92-3.83 JH,, CHala), 3.59 (1H, bs, NHala), 3.06-2.98 (1H, m, H4 '), 2.93 (1H, bs, CHcPr), 2.74-2.63 (1H, m, 1 of H6'), 1.62-1.53 (1H, m, 1 of H6 '), 1.34-1.18 (3H, m, CH3 wing.), 1.15-1.11 (6H,, CH (CH3) 2), 0.79-0.73 (2H, q, 2H of CH2cPr), 0.53 (2H, bs, 2H of CH2cPr). 13 H NMR: 173.5 (CO) 159.8 (C2), 156.2 (C4), 151.1 (C6), 151.0 ('? Pso'-Ph), 136.9 (C2'), 136.1 (C8), 131.3 (C3 ') , 130.0 (m '-Ph), 125.3 Pp'-Ph), 120.5 Ph) 115.0 (C5), 69.6 (C5') 69.2 (OCH) 59.3 (Cl ') 50. 7 (CHala), 46.0 (C4 '), 34.9 (C6'), 24.2 (CHcPr), 22.0 (CH (CH3) 2), 21.4 (CH3ala), 7.8 (CH2cicl.).

MS ES +: m / z 555.9 (100%, M +), 556.9 (30%, M + H +). MS MALD / I TOF: For C26H35? 5N7P, found - 555,575. HPLC: tR 35.85 (100%) - (100% water (0 min), % water (35 min), 20% water (45 min), 100% water (55 min)). phenyl-Butyloxy-L-alaninyl phosphorochloridate phenyl. C? 6H? 704N1Cl1P ?, MW = 353.74. This was synthesized according to I the Normalized Procedure 3, using L-alanine tert-butyl ester hydrochloride (0.5 g, 2.75 mmol), PhOP (0) Cl2 (0.41 ml, 2.75 mmol) and NEt3 (0.77 ml, 5.5 mmol), yielding 0.77 g (87.5%) of crude product which was stored with THF anhydride (5 ml), providing a solution of 0.48 mmol / ml which was used without further purification. 31P NMR: d 9.53, 9.20 (1: 1). NMR of? E: d 7.44-7.39 (2H, t, O'-Ph), 7.32-7.26 (3H, m, m '+' p'-Ph), 4.47-4.34 (1H, m, NHala), 4.17 -4.04 (1H,, CHala), 1.53 (9H, 3s, 3xCH3). 13 C NMR: d 170.7 (CO), 148.7 ('' ipso rÍPh), 128.9 (O'-Ph), 124.9 (? P '-Ph), 119.5 (* m'-Ph), ¿1.65 (CMe3), 50.0 (CHala), 26.9 (3xCH3).

O- (phenyl-tert-butyloxy-L-alaninyl) -phosphate of (1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol. Cf 1645. C24H30O5N7P1, MW = 603.6. This was synthesized according to l Standard Procedure 4, using (ÍS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol (140 mg, 0.52 mmol), tBuMgCl (1.05 ml, 1.05 mmol of a 1.0M solution in THF) and phenyl (tert-butyloxy-L-alaninyl) -phosphorochloridate (3.3 ml, 1.57 mmol, from a 0.48M solution in THF), in anhydrous THF ( 4 ml), stirring at room temperature for 48 h. The crude product was purified by eluting with 3% MeOH in CHC13, affording the pure product as a white foamy solid (192.3 mg, 69.0%). 31P NMR: d 4.15 (s). XH NMR: d 7.40 (1H, d, l = 8.35Hz, H8), 7.23-7.18 (2H, t, * m'-Ph), 7.12 (2H, d, O'-Ph), 7.06 -7, 02 (1H, t,? P'-Ph), 6.09 (1H, bs, H2 '), 5.97 (1H, bs, H3'), 5.77 (1H, d, NHcPr), 5.44 (1H, bs, Hl ' ), 5.10 (2H, bs, NH2), 4.14-4.05 (3H, m, H5 '+ NHala), 3.85-3.77 (1H, q, CHala), 3.04 (1H, bs, H4'), 2.93 (1H, bs, CHcPr), 2.72-2.62 (1H, m, 1 of H6 '), 1.58-1.53 (1H, t, 1 of H6'), 1.34 (9H, d, CMe3), 1.27-1.23 (3H, t, CH3ala), 0.73 (2H, d, 2H of CH2cPr), 0.51 (2H, bs, 2H of CH2cPr).

NMR of 113J, C: d 173.2 (CO), 160.4 (C2), 156.7 (C4), 151.2 (C6 + "ipso'-Ph), 136.8 (C2 '), 135.9 (C8), 131.5 (C3'), 130.0 (m'-Ph), 125.2 (* p'-Ph), 120.6 ('P' ~ Ph), 115.2 (C5), 82.3 (C [CH3] 3) / 69.3 (C5 '), 59.1 Cl'), 46.0 (C4 '), 35.0 (C6'), 28.3 (3xCH3), 24.2 (CHcPr), 21.5 (CH3ala), 7.8 (CH2CPr) MS ES +: m / z 570.0 (100%, M +), 570.9 (32% , M + H + MS FAB: For C27H37O5N7P requires 570.2594, found 570.259 S. HPLC: tR 36.158 (100%) - (100% water (0 min), 20% water (35 min), 20% water ( 45 min), 100% water (55 ml?).

N-pentyl ester hydrochloride salt of L-alanine C8HI6NI02C1: L, MW = 195.69 This was synthesized according to Standard Procedure 1, using pentan-1-ol (36.3 ml, 0.337 mol), thionyl chloride (4.92 ml, 67.4 mmol) and L-alanine (3.0 g, 33.7 mmol). The product was isolated as a pure product in the form of a white solid (4.86 g, 73.7%). NMR of? E (MeOH-d4): d 4.32-4.20 (2H, m, 0C 2), 4.16-4.08 (1H, m, CHala), 1.77-1.68 (2H,, OCH? CH2), 1.56 (3H, d, J = 7, 22Hz, CH 3ala), 1.42-1.36 (4E, m, CH 2 CH 2 CH 3), 0.97-0.93 (3H, m, CH 2 CH 3). - ail »NMR of 13J, C: d 170.1 (CO), 66.5 (OCH2), 48.8 CHala), 28.2 (OCH2CH2), 28.0 (CH2CH2CH3), 22.3 (CH2CH3), 15.2 (CH3ala), 13.3 (CH2CH3). (n-Pentoxy-L-alaninyl) -phenyl phosphorochloridate C? 4H2? N? 04P? Cl ?, MW = 333.78 This was synthesized according to Standard Procedure 3, using the hydrochloride salt of the n-pentyl ester of L- alanine (0.5 g, 2.56 mmol), PhOP (0) Cl2 (0.38 mL, 2.56 mmol), triethylamine (0.71 mL, 5.11 mmol) in DCM (60 mL). The usual treatment gave the crude product as a yellow oil (0.79 g, 92.6%), which was stored with THF (5 ml), providing a 0.47M solution. 31 P NMR: d 9.39, 9.12 (1: 1). 2 H NMR: d 7.43-7.38 (2H, m, O'-Ph), 7.32-7.25 (3H, m, xm '+' p'-Ph), 4.63 (1H, broad d, NHala), 4. 24-4.11 (3H, m, OCH2 + CHala), 1.73-1.65 (2H m, 0CH2CH2), 1.57-1.53 (3H, dd, CH3ala), 1.42-1.35 (4 H, m, 2xCH2), 0.97-0.91 ( 3H, m, CH2CH3). NMR of 13, d 173.1 (CO), 150.1 (lipso '\ - Ph) 130. 3 (* m'-Ph), 126.4 (* p '-Ph), 121.0 (O'-Ph), 66.5 (OCH2), 51.0 (CHala), 28.6 (CH2-C2), 28.3 (CH2-C3), | 22.7 (CH2-C4), 21.0 (CH3ala), 14.1 (CH3-C5).

O-Phenyl- (n-pentyloxy-L-alaninyl) -phosphate from (1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol. Cf 1Y06. C28H38N705 ?, PM = 583.7 This was synthesized according to Standard Procedure 4, using (SS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene- 1- methanol (100 mg, 0.35 mmol), tBuMgCl (0.7 ml, 0.7 mmol, of a 1.0 M solution in THF), in THF (3 ml) and (n-pentyl-L-alaninyl) phenylphosphorochloride (2.22 mJ, 1.05 mmol, from a 0.47 M solution in THF), at room temperature for 24 h. The crude product was purified by elution with 2.5-3.0% MeOH in CHC13 (x2), affording the pure product as a pale yellow foamy solid (143.2 mg, 70.2%). 31P NMR: d 3.99, 3.95 (1: 1). NMR of? E: d 7.41 (1H, d, j = 7.18 Hz, H8), 7.24-7.19 (2H, m, O'-Ph), 7.12-7.02 (3H, m, m '+ * p' | -Ph), 6.09 (1H, bs, NHcPr), 5.98 (1H, d, H2 '), 5.79 (IHI bs, H3'), 5.44 (1H, bs, Hl '), 5.09 (2H, bs, NH2) , 4.16¡-3.88 (6H,, CHala, OCH2, H5 '+ NHala), 3.05 (1H, bs, H4'), 2. 94 (1H, bs, CHcPr), 2.73-2.63 (1H, m, 1 of H6 '), 1.62-1.51 (3H, m, 1 of H6' + OCH2CH2), 1.31-1.21 (7H, t, CH3ala + 2xCH2), 0.81-0.74 (5H,, CH3 + 2H of CH2cPr), 0.52 (2H, bs, 2H of CH2cPr). 13 C NMR: 174.1 (CO), 160.1 (C2), 156.5 C4), 151.2 (C6), 151.1 ('ipso' -Ph), 136.8 (C2 '), 136.1 C8), 131.5 (C3'), 130.0 (* m '-Ph), 125.2 (* p' -Ph), 120.5 O'-Ph), 115.1 (C5), 69.3 (C5 '), 66.1 (OCH2), 59.3 (Cl'), 50.7 (CHala) , 46.0 (C4 '), 34.9 (C6'), 28.6 (Cí2-C2), 28.3 (CH2-C3), 24.2 (CHcPr), 22.6 (CH2-C4), 21.5 (CH3ala), 14.3 (CH3-C5) 7.8 (CH2CPr). MS ES +: m / z 584.2 (100%, M +), 585.2 (25%, M + H +) MS FAB: For C28H39? 5N7P requires 584.2750, found 584.2757. HPLC: tR 40.294 (99.3%) - (100% water (0 min. 20% water (35 min.), 20% water (45 min.), 100% water (55 min.).

N-Hexyl ester hydrochloride salt of L-alanine C9H20N? 2Cl ?, MW = 209.75 This was synthesized according to | Standard Procedure 2, using L-alanine (2.0 g, 22.5 mmol), hexan-1-ol (2.82 mL, 22.5 mmol), p-toluene sulfonic acid monohydrate (4.7 g, 24.7 mmol), and toluene (100 mL) . The n-hexyl ester hydrochloride of L-alanine was isolated as a white powdery solid (3.32 g, 70.5%). NMR of? E (MeOH-d4): d 4.31-4.18 (2H, m, C? CH2), 4.17-4.09 (1H, q, CHala), 1.75-1.66 (2H, m, OCHJCH2), 1.57 (3H, d, J = 7.20Hz, CH3ala), 1.45-1.35 (6H, m, [CH2] 3CH3), 0.94-0.89 (3H, t, CH2CH3). 13 C NMR: 170.1 (CO), 66.5 (OCH2), 48.9 (CHala), 31.6 (OCH2CH2), 28.6 (O [CH2] 2CH2), 25.6 (CH2CH2CH3), 22.6 (CH2CH3), 15.4 (CH3ala), 13.4 (? H2CH3). (n-bexyloxy-L-alaninyl) -phenyl phosphorochlorurate C? 5H23N? 04P? Cl ?, MW = 34? .81 This was synthesized in accordance with Standard procedure 3, using the hydrochloride salt of the n-hexyl ester of L-alanine (0.5 g, 2.38 mmol), PhOP (0) Cl2 (0.36 ml, 2.38 mmol), triethylamine (0.66 ml 4.77 mmol) in DCM (60 ml). The habitat treatment gave the crude product as a yellow oil (0.69 g, 83.2%), which was stored with THF (4 ml), providing a 0.496M solution. 31 P NMR: 9.40, 9.10 (1: 1). 2 H NMR: d 7.44-7.14 (5H, m, OPh), 4.25 (1H, bs, NHala), 4.23-4.03 (3H, m, OCH2 + CHala), 1.70-1.63 (2H,, CH2-2), 1.57-1.54 (2H, m, CH2-3), 1.47-1.32 (7H, m, CH3ala + 2CH2-4.5), 0.93-0.91 (3H, dd, CH3-6). NMR of 13, d 173.2: co) 150.1 ('ipso' -Ph) 130. 3 (-.m'-Ph), 126.4 (* p'-Ph), 120.9 (O'-Ph), 66.4 (OCH2), 51.0 (CHala), 31.7 (CH2-C2), 28.9 (CH2-C3) , 25.8 (CH-C4), 22.9 (CH2-C5), 21.0 (CH3ala), 14.4 (CH3-C6) 1. • a &t O-Phenyl- (n-hexyloxy-L-alaninyl) -phosphate of (SS, 4R) -4- (2-a-ino-6-cyclopropylamino-9H-purin-9-yl) -2- Cyclopentene-1-methanol. C29H4oN705P ?, MW = 597.651 This was synthesized according to Standard Procedure 4, using (ÍS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-ethanol ( 100 mg, 0.35 mmol), tBuMgCl (0.7 ml, 0.7 mmol, of a 1.0 M solution in THF), in THF (3 ml) and phenyl (p-2-oxyhexyl) phenylphosphorochloride (2.JL1 ml, 1.05 mmol, of a 0.496 M solution in THF), at room temperature for 24 h. Additional phenyl (n-hexoxy-L-alaninyl) -phosphorochloridate (1 J 5 mL, 0.68 mmol, of a 0.496 M solution in THF) was added, and the reaction was stirred for another 24 hours. The crude product was purified by elution with 3.0% MeOH in CHCl3 (x2), affording the pure product as a pale yellow foamy solid. 31 P NMR: d 3.94, 3.91 (1: 1). XH NMR: d 7.52 (1H, d, J = 8.00Hz, H8), 7.36-7.31 (2H,, O'-Ph), 7.25-7.15 (3H,, m '+ * p'-Ph), 6.26 (1H, bs, NHcPr), 6.13-6.08 (1H, m, H2 '), 5.93-5.88 (1H, m, H3'), 5.58-5.53 (1H, m, Hl '), 5.14 (2H, bs , NH2), 4.28-3.89 (6H, m, CHala, OCH2, H5 '+ NHala), 3.17 (1H, t, H4'), 3.04 (1H, bs, CHcPr), 2.87-2.75 (1H, ¡, 1 of H6 '), 1.74-1.61 (3H, m, 1 of H6' + OCH2CH2), 1.43-1.31 (9H, t, CH3ala + 3xCH2), 0.92-0.85 (5H, m, CH3 + 2H of CH2cPr), 0.68-0.63 (2H, q, 2H of CH2cPr). 13 C NMR: 174.1 CO, 160.1 (C2), 156.5 (C4), 151.2 (C6), 151.1 ('ipso' -Ph), 136.9 (C2 '), 136.0 (C8), 131.4 (C3'), 130.0 (m'-Ph), 125.3 (p'-Ph), 120.5 ('o'-Ph), 115.0 (C5), 69.2 (C5'), 66.1 (OCH2), 59.3 Cl '), 50. 7 (CHala), 46.0 (C4 '), 34.9 (C6'), 31.7 (OCH¡ ¡2CH2), 28. 8 (CH2-ester), 25.8 (CH2-ester), 24.2 (CHcPr), 21.9 (CH2-ester), 21.5 (CH3ala), 14.4 (CH3-ester), 7.8 (CH2cPr).

Hydrochloride salt of the cyclohexyl ester of L-alaniria This was synthesized according to Standard Procedure 2, using L-alanine (2.0 g, 22.5 mmol), cyclohexanol (2.34 ml, 22.5 mmol), p-toluene acid its lphonic monohydrate (4.7 g, 24.7 mmol), and toluene (100 mL). The p-toluene sulfonate salt was isolated as a pale orange solid (1.45 g). The reaction was repeated using L-alanine (3.0 g, 33.7 mmol), cyclohexanol (5.26 ml, 50.6 mmol), p-toluene sulfonic acid monohydrate (9.62 g, 50.6 g or toluene (100 ml) .The hydrochloride salt of the cyclohexyl ester of L-alanine was isolated as a white solid (3.15 g, 45.45%). XH NMR (MeOH-d4): d 4.90 (1H, m, OCH), 4.12-4.04 (1H, q, CHala), 1.92- 1.81 (2H, m, OCHCH2), 1.80-1.63 (2H, m, OCHCH2), 1.55 (3H, d, J = 7.23Hz, CH3ala), 1.49-1.33 (6H,, [CH2] 3). 13 C NMR : d 169.5 (CO), 75.4 (OCH), 48.9 (CHala), 31.3 (2 x CH2-o), 25.2 (2 x CH2-m), 23.5 (p- CH2), 15.3 (CH3ala). (p-hexyloxy-L-alaninyl) -phenyl phosphorochloride CIS ^ INÍOÍPICII, MW = 345.79 This was synthesized according to Standard Procedure 3, using hydrochloride salt of the cyclohexyl ester of L-alanine (0.7 g, 3.4 mmol), PhOP (0) Cl2 (0.51 mL, 3.4 mmol), triethylamine (0.95 mL 6.8 mmol) in DCM (60 mL). The usual treatment gave the crude product as a yellow oil (1.12 g, 95.2%), which was stored with THF (7 ml), yielding a 0.46 M solution. 31 P NMR: d 9.43, 9.07 (1: 1) NMR from 1H: d 7.44-7.33 (2H, m, O'-Ph), 7.32-7.20 (3H, m, * m '+ Xp'-Ph), 4.92-4.83 (1H.m, OCH), 4.55- 4.42 (1H, m, NHala), 4.28-4.15 (1H, m, CHala), 1.89 (2H, bd, CH2- '?'), 1.76 (1H, bd, CH2-x? '), 1.54 (3H, d, CH3ala), 1.49-1.32 (6H, m, CH33CH2- 'm' + * p '). 13 C NMR: d 172.5 (CO), 150.1 ('ipso' -Ph), 130.3 (* m'-Ph), 126.4 ('p'-Ph), 121.0 (O'-Ph), 74.9 (OCH), 51.1 (CHala), 31.8 (CH2-? O '), 25.6 (CH2- * p'), 21.0 (CH3ala).

O-Phenyl- (C-hexyloxy-L-alaninyl) -phosphate of (1S, 4R) -4-r (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol . Cf 1707. C29H38N705P ?, MW = 595,635 This was synthesized according to Standard Procedure 4, using (ÍS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2- cyclopentene-1-methanol (100 mg, 0.35 mmol), tBuMgCl (0.7 ml, 0.7 mmol, from a 1.0 M solution in THF), in THF (3 ml) and (p-hexoxy-L-alaninyl) -phosphorochloride phenyl (2.28 ml, 1.05 mol, of a 0.46 M solution in THF), at room temperature for 24 h. The crude product was purified by elution with 34% MeOH in CHCl3, and then 2.5-3.0% MeOH in CHC13, affording the pure product as a pale yellow solid (199 mg, 95.7%). 31 P NMR: d 4.06, 3.99 (1: 1). 1 H NMR: 7.42 (1H, d, J = 8.15 Hz, H8), 7.23-7.18 (2H,, O'-Ph), 7.12-7.02 (3H, m, * m '+? P' jph), 6.31 (1H, bs, NHcPr), 5.98 (1H, bs, H2 '), 5.78 (_J H, bs, H3 '), 5.43 (1H, bs, Hl' 5.21 (2H, bs, NH2 4.66 (1H, bs, OCH), 4.17-4.02 (3H, m, H5 '+ NHala), 3.95-3.85 (1H,, CHala ), 3.05-2.94 (2H, m, H4 '+ CHcPr), 2.73-2.63 (1H,, 1 of H6'), 1.69 (2H, bs, CH2-'o '), 1.62-1.53 (2H, m, CH? O '), 1.45-1.18 (9H, m, CH3ala + 3xCH2-' m '+' p ') i 0.76 (2H, d, 2H of CH2cPr), 0.53 (2H, bs, 2H of CH2cPr) 13C NMR: 172.0 CO, 158.4 (C2), 154 (C4), 149. 7 (C6), 149.6 ('ipso'-Ph), 135.5 (C2'), 134.7 (C8), 130.0 (C3 '), 128.6 (* m' -Ph), 123.8 ('p'-Ph), 119 lj ('o'- Ph), 113.1 (C5), 72.9 (OCH), 67.8 (C5'), 57.9 (Cl <), 59. 4 (CHala), 44.7 (C4 '), 34.5 (C6'), 30.3 (CH2 | - o '), 24. 2 (CH2-? M '), 22.8 (CHcPr), 22.5 (CH2-'p'), - 20.1 (CH3ala), 6.4 (CH2cPr). MS ES +: m / z 596.2 (100%, M +), 597.3 (20%, M + H +; MS FAB: For C29H39? 5N7P requires 596.2750, found 596. 2750. HPLC: tR 40.502 (99.8%) - (100% water (0 min) % water (35 min), 20% water (45 min), 100% water (55 min)) • L-Alahine C? OH2O? 02Cl? Methyl cyclohexane methyl chlorohydrate, MW = 221.75 This was synthesized according to the Standard Procedure 2, using L-alanine (3.0 g, - ^^^ 33.7 mmol), cyclohexanemethanol (4.15 mL, 33.7 mmol), p-toluene sulfonic acid monohydrate (7.05 g, 37.1 mmol), and toluene (100 mL; 9.2 g of the salt were dissolved in DCM (50 mL). PTSA and washed with 10% K2CO3 (50 ml), and water (2x50 ml), dried over MgSO4, filtered and the filtrate was reduced to dryness to give a yellow oil. This was neutralized with 2M HCl, stirred for 2 hours. hours and then lyophilized to give the hydrochloride salt as a white solid (4.32 g, 75.8%). XH NMR (MeOH-d4): d 4.19-4.01 (3H, m, OCH + CHala), 1.79-1.69 ( 5H, m, CH + or -CH2), 1.58 (3 | H, d, J = 7.21 Hz, CH3ala), 1.37-1.20 (4H, m, m-CH2), 1.09-0.98 (2H, q, p- CH2). 13 C NMR: 170.1 (CO), 71.3 (OCH2), 48.9 (CHala), 37.3 (CH), 29.5 (2xCH2-o), 26.4 (p-CH2), 25.7 (2xCH2-m), 15.4 (CH3aJ.a).

(Cyclohexane-methoxy-L-alaninyl) -phenyl phosphorochloride This was synthesized according to Standard Procedure 3, using the hydrochloride salt of the cyclohexanemethyl ester of L-alanine (0.7 g, 3.16 mmol), PhOP (0) Cl2 (0.47 ml, 3.16 mmol), triethylamine (0.88 ml, 6.31 mmol) in DCM (70 ml). The usual treatment gave the crude product as a yellow oil (1.10 g, 96.8%), which was stored with THF (6 ml), yielding a 0.51 M solution. 31 P NMR: 9.35, 9.05 (1: 1). NMR of XH: d 4.61-4.50 (1H, q, NHala), 4.28-4.13 (1H, m, CHala), 4.04-4.00 (2H, q, 0CH2), 1.78-1.74 (7H, t, CHcHx + xo'- CH2), 1.57-1.54 (3H, dd, CH3ala), 1.06-0.96 (2H, q,? P'-CH2). 13 C NMR: d 173.1 (CO), 150.1 ('ipso' -Ph), 130.3 ("m'-Ph), 126.4 (p'-Ph), 121.0 (O'-Ph), 71.4 (OCH2), 51.0 (CHala), 37.4 (CHcHx), 29.9 (CH2- or '), 26.7 (CH2-? M'), 25.9 (CH2- xp '), 21.1 (CH3ala).

O-phenyl- (cyclohexane-methoxy-L-alaninyl) -phosphate of (1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol. Cf 1708. C30} I40NnOsP ~ PM = 609.66 This was synthesized in accordance with Standard Procedure 4, using (ÍS, R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-l-methanol (100 mg, 0.35 mmol), tBuMgCl (0.7 ml, 0.7 mmol, of a 1.0 M solution in THF), in THF (5 mil) and phenyl (cyclohexane-methoxy-L-alaninyl) -phosphorochlorurate 1 (2.06 ml, 1.05 mmol, from a 0.51 'M solution in THF) at room temperature for 48 h. The crude product was purified by eluting with 4-6% MeOH in ECM, and then 3% MeOH in CHCl3 to give the crude product as a pale yellow foamy solid (161.1 mg, 75.6%). 31P NMR: d 3.99, 3.92 (1: 1). NMR of? E: d 7.40 (1H, d, J = 7.07 Hz, H8), 7.24-7.19 (2H, t, O'-Ph), 7.13-7.03 (3H, m, * m '+? P'- Ph), 6.00-5.96 (2H, m, H2 '+ NHcPr), 5.79 (1H, q, H3'), 5.45 (1H, d, H1 '), 5.05 (2H, bs, NH2), 4.16-4.01 ( 3H, m, OCH2 + NHala), 3.98-3.88 (1H, m, CHala), 3.86-3.74 (2H, m, H5 '), 3.07-3.00 (1H, t, H4'), 2.94 (1H, bs, CHcP.}. :), 2.74-2.63 (1H, m, 1 of H6 '), 1.88-1.50 (7H, m, CHcHx + 2CH2-?'), 1.31-1.27 (3H, t, CH3ala), 1.21 -0.99 (4H, m, 2CH2-m '), 0.89-0.79 (2H, q, CH2- * p'), 0.75 ; 2H, d, 2H of CH2cPr), 0.54-0.50 (2H, t, 2H of CH cPr; 13C NMR: 174.1 (CO), 160.2 (C2), 156.4 (C4), 151.2 (C6), 151.1 ( 'ipso' -Ph), 136.7 (C2 '), 136.0 (C8), 131.5 (C3'), 130.0 (? m'-Ph), 125.2 (* p'-Ph), 120.5 (O'-Ph), 115.1 (C5), 71.0 (OCH2), 69.3 (C5 '), 1 59.3 (Cl'), 50.7 (CHala), 46.1 (C4 '), 37.4 (CHcHx), I 34.9 (C6) '), 29.9 (CH2-' or '), 26.6 (CH2- * m'), 25.9 (CH2- p '), 24. 2 (CHcPr), 21.5 (CH3ala), 7.8 (CH2cPr). MS ES +: m / z 610.3 (50%, M + H +), 632.3 (100%, M + Na +), 633.3 (M + H + Na +).

MS FAJ3: For C3oH4o05N7NaP requires 632.2726, found 632.2710. HPLC: tR 42.859 (100%) - (100% water (0 min), 20% water (35 min), 20% water (45 min), 100% water (55 min)). 4-Chlorophenyl 4-chlorophenylphosphorodichloride C6H402P? Cl3, MW = 246.43 Phosphorus oxychloride (2 ta.l, 21.5 mmol) was stirred with anhydrous diethyl ether (70 ml) in a 250 ml round bottom flask. To this was added, dropwise, a solution of 4-chloropropanol (2.1 ml, 21.5 mmol) and anhydrous triethylamine (3.0 ml, 21.5 mmol) in anhydrous diethyl ether (30 ml) at -80 ° C. This solution was stirred vigorously at -80 ° C for 1 hour and allowed to rise to room temperature for 16 hours. The triethylamine hydrochloride salt was removed by filtration and the filtrate was reduced to dryness to give the crude product as a yellow oil (4.61 g, 87.2%). 31P NMR: d 4.99 (s). 13 C NMR: d 148.4 ('ipso' -Ph), 133.2 (* p'-Ph), 130.7 (* m'-Ph), 122.4 (O'-Ph). £ -k - »-» «- * > • &- (Metoxy-L-alaninyl) -phosphorochloride 4-chlorophenyl C? 0H? 2N? OP? Cl2. MW = 246.43 This was synthesized according to Standard Procedure 3. using L-alanine methyl ester hydrochloride (2.61 g, 18.7 mmol) and p-chlorophenyl phosphorodichloride (4.61 g, 18.7 mmol) and triethylamine (5.21 ml, 37.4 mrnol) in anhydrous DCM (100 ml). The usual treatment gave the crude product as a crude, colorless oil (3.76 g, 64.4%), which was stored with anhydrous THF (20 ml) providing a 0.6M solution which was used without further purification. 31P NMR: d 9.48. 9.25 (1: 1). XH NMR: d 7.36 (2H, d, J = 8.20Hz,? O''-Ph), 7.32-7.22 (2H, m, m '-Ph), 4.69 (1H, d, NHala), 4.27- 4.15 (1H, m, CHala), 3.82 (3H, d, OCH3), 1.56-1.53 (3H, dd, J = 7.04 Hz, CH3ala). 13 C NMR: d 173.4 (CO), 148.6 ('ipsof -Ph), 131.9 Pp'-Ph), 130.3 (m'-Ph), 122.3 (O'-Ph), 1 53.2 (OCH3), 50.9 (CHala ), 20.9 (CH3ala).

O- [4-chlorophenyl- (methoxy-L-alaninyl)] -phosphate of (1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) i -2-cyclopentene-1 -methanol, Cf 1620. C24H29N7? 5P? Cl ?. MW = 562.02 This was synthesized according to Standard Procedure 4. using (ÍS, 4R) -4- (2-amino-6-cyclopropylamino- 9H-purin-9) -yl) -2-cyclopentene-1-methanol (250 mg, 0.87 mmol), rBuMgCl (1.75 mL, 1.75 mmol of a 1.0 M solution in THF), and 4-chlorophenyl (methoxy-L-alaninyl) -phosphoroclorurate (4.37 mL, 2.62 mmol, of a 0.6 M solution in THF) , in anhydrous THF (13 ml), stirring at room temperature for 24 h. The crude product was purified by elution with 3% MeOH in CHC1 to give the pure product as a white foamy solid (364.5 mg, 74.5%). 31 P NMR: d 4.01 (s). 1 H NMR: 7.42 (1H, d, H8), 7.22-7.17 (2H,, * m'-Ph), 7.09-7.03 (2H, t, O'-Ph), 5.99 (1H, d, H2 ') ), 5.93 (1H, s, H3 '), 5.83 (1H, bs, NHcPr), 5.45 (1H, bs, Hl'), 4.96 (2H, bs, NH2), 4.11 (2H, bs, H5 '), 4.Q3-3.86 (1H,, CHala), 3.62 (3H, s, OCH3), 3.07 (1H, d, J = 5.9 Hz, H4 '), 2.92 (1H, bs, CHcPr), 2.76-2.64 (1H , m, 1 of H6 '), 1.64-1.59 (1H, t, 1 of H6'), 1.32-1.26 (3H, q, CH3ala), 0.76 (2H, d, J = 6.40 Hz, 2H of CH2cPr), 0.53 (2H, bs, 2H of CH2cPr). 13 C NMR: 174.4 (CO), 160.4 (C2), 156.7 (C4), 151.3 (C6), 149.7 ('ipso' -Ph), 136.7 (C2 '), 135.9 (C8), 131.6 (C3) '), 130.5 (* p'-Ph), 130.0 (* m'-Ph), 121.9 (O'-Ph), 115.2 (C5), 69.4 (C5'), 59.25 (Cl '), 52.9 (OCH3) ), 50.6 (CHala), 46.0 (C4 '), 34.9 (C6'), 24.1 (CHcPr), 21.4 (CH3ala), 7.8 (CH2cPr). HPLC: tR 32.693. 33.012 (100%) - (100% water (0 min), 20% water (35 min), 20% water (45 min), 100% water (55 min)). 4-bromoenyl phosphodichloride C6H40Cl2Br ?. MW = 289.87 This was synthesized by a procedure analogous to that of 4-chlorophenyl phosphorodichlorurate, except that phosphorus oxychloride (3.29 g, 2 ml, 21.5 mmol) and 4-bromophenol (3.71 g, 21.5 mmol) and ether were used. anhydrous diethyl ether (70 ml), and anhydrous triethylamine (2.71 g, f3 ml, 82. 6%). NMR of 3iP: d 4.88 (s). NMR of? E: d 7.63 (2H, d, J = 8.14 Hz, O'-Ph), 7.28 (2H, t, * m'-Ph). 13 C NMR: d 1 ^ 9.0 ('ipso' -Ph), 133.7 ("m'-Ph), 122.6 (O'-Ph), 120.9 (* p'-Ph).

(Metoxy-L-alaninyl) -phosphoroclorurate of 4-bromophenyl C? 0H? 2? O4P? Cl? Br ?. MW = 356.55 This was synthesized according to Standard Procedure 3. using the hydrochloride salt of L-alanine methyl ester (1.0 g, 7.16 mmol), 4-bromophenyl phosphorodichloride (1.82 g, 7.16 mmol), triethylamine (2 ml 14.3 mmol) in DCM (70 ml). The usual treatment gave the crude product as a yellow oil (2.24 g, 87.7%), which was stored with THF (12 ml), yielding a 0.524 M solution. 31 P NMR: d 9.16. 9.10 (1: 1) 13 C NMR: d 173.4 (CO), 150.1 ('ipso -Ph), 133.3 (* m'-Ph), 122.7 (O'-Ph), 119.6 (* p' -Ph), 53.3 (OCH3), 51.0 (CHala), 20.9 (CH3ala).

O- [4-bromo-phenyl- (methoxy-L-alaninyl) 1-phosphate of (1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1- methanol Cf 1710. C24H29N705P? Br ?. MW = 606.42 This was synthesized according to Standard Procedure 4. using (ÍS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol (100 mg, 0.35 mmol), tBuMgCl (0.7 mL, 0.7 mmol, of a 1.0 M solution in THF), THF (5 mL) and 4-bromophenyl (methoxy-L-alaninyl) -phosphorochloride (2.0 mL, 1.05 mmol , of a 0.524 M solution in THF), at room temperature for 24 h. The crude product was purified by elution with 4-6% MeOH in DCM, and then in 4% MeOH in DCM, affording the pure product as a white foamy solid (115.2 mg, 54.4,%). 31P NMR: d 3.96 (s). XH NMR: 7.42 (1H, d, H8), 7.34-7.3.0 (2H, dd, J = 8.73 Hz, O'-Ph), 7.03-6.97 (2H, t, J = 8.68 Hz, m ' -Ph), 6.02-5.97 (2H,, H2 '+ NHcPr), 5.83-5.79 (1H, m, H3'), 5.43 (1H t, Hl '), 5.06 (2H, bs, NH2), 4.2¡8 -4.04 (3H, m, H5 '+ NHala), 4.02-3.85 (1H,, CHala), 3.61 (3H, d, OCH2), 3.05 (1H, d, J = 6.09 Hz, H4'), 2.94 (1H , d, CHcPr), 2.75-2.66 (1H, m, 1 of H6 '), 1.66-1.56 (lHl, m, 1 of H6'), 1.31-1.25 (3H, dd, CHjala), 0.79-0.72 (2H , q, 2H of CH2cPr), 0.54-0.49 (2H, t, 2H of CH2cPr). 13 C NMR: 174.4 (CO), 160.3 (C2), 156.6 (C4), 151.3 (C6) 150.2 ('ipso' -Ph), 136.7 (C2 '), 136.0, (C8), 133.0 ("m') -Ph), 131.6 (C3 '), 122.4 (O'-Ph), 118.1 (? P' -Ph), 115.2 (C5), 69.4 (C5 '), 59.3 (Cl'), 52.9 (¡OCH3), 50.6 (CHala), 46.0 (C4 '), 34.8 (C6'), 24.2 (CHcPr), 21.3 (CH3ala), 7.8 (CH2CPr). S ES +: m / z 606.13 (40%, M +), 628.1065 (100% , 79-M + Na +), 630.0967 (95%, 81-M + Na +).

MS FAB: For C24H2905N7NaPBr requires 628 1049 found 628.1058. and C24H29? 5N7NaP JBr requires 630.1028. found 630.1042. HPLC: tR 35.882 (100%) - (100% water (0 min), 20% water (35 min), 20% water (45 min), 100% water (55 i?)). 4-Fluorophenyl Phosphorodichlorurate C6H02P? Cl2F1. PM = 228.97 This was synthesized by a procedure analogous to that of 4-chlorophenyl phosphorodichlorurate, except that it was used: phosphorus oxychloride (3.29 g, 2 ml, 21.5 mmal) and 4-fluorophenol (2.41 g, 21.5 mmol) in diethyl ether anhydrous (70 ml) and anhydrous triethylamine (2.71 g, 31 i, 21.5 mmol), in anhydrous diethyl ether (30 ml). | The reaction was stirred at -80 ° C for 4 hours and then at room temperature for 2 hours. After filtration and removal of the solvent, the product was obtained as a clear liquid (4.08 g, 83.0%). 31P NMR: d 5.50 (s). NMR of? E: d 7.29-7.24 (2H, m, O'-Ph), 7.09 (2H, t, J = 8.29 Hz, -m'-ph). 13 C NMR: 159.7 ('ipso' -Ph), 145.8 (m 'ph), 122.6 (O'-Ph), 117.5 (? P'-Ph). , (Metoxy-L-alaninyl) -phosphoclorurate of 4-fluorophenyl C? OH12Nx0P? Cl? F ?. MW = 295.65 This was synthesized according to cor. Standard Procedure 3. using the hydrochloride salt of the L-alanine methyl ester (1.0 g, 7.16 mmol), 4-fluorophenyl phosphorodichloride (1.64 g, 7.16 mmol), triethylamine (2 mL, 14.3 mmol) in DCM (70 mL). The usual treatment gave the crude product as a yellow oil (1.97 g, 93.0%), which was stored with THF (12 ml), providing a 0.56 MJ NMR solution of 13P: d 9.84. 9.60 (1: 1). 2 H NMR: d 7.32-7.23 (2H, m, O'-Ph), 7.12-7.06 (2H, m,? M'-Ph), 4.69 (1H, bs, NHala), 4.22J (1H, bs , CHala), 3.82 (3H, d, OCH3), 1.57-1.53 (3H, m, CH3ala). 13 C NMR: d 173.5 (CO), 161.6 ('ipso' -Ph), 145.9 (* m'-Ph), 122.5 (? O'-Ph), 117.0 (* p'-Ph), 53.2 (OCH3) , 50.9 (CHala), 20.9 (CH3ala).

O- [4-fluorophenyl- (methoxy-L-alaninyl) 1-phosphate (1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) | -2-ciel open dye -1-methanol. Cf 1737. C2 H29N705P1F ?. PM = 545.57 This was synthesized according to the Normalized Procedure 4. using (ÍS, 4R) -4- (2-amino- cO. . 6-cyclopropylamine-9H-purin-9-yl) -2-cyclopentene-1-methanol (100 mg, 0.35 mmol), tBuMgCl (0.7 ml, 0.7 mmol, of a 1.0 M solution in THF), in THF (5 ml ) and 4-fluorophenyl (methoxy-L-alaninyl) -phosphorochloridate (1.89 ml, 1.05 mmol, from a 0.56 M solution in THF), at room temperature for 24 h. The solvent was removed under reduced pressure and the residue was treated on a column with 2.5-5% methanol in chloroform and then in 3% methanol in chloroform, affording the pure product as a pale yellow foamy solid (62.0 mg, 32. 5%) • NMR of 3J1 ±, P: d 4.24. 4.23. 4.20. 4.19, NMR of X: d 7.52 (1H, d, H8), 7.21-7.14 (2H, m, O'-Ph), 7.03-6.97 (2H, m, * m '-Ph), 6.16 (1H, ps , NHcPr), 6.10-6.07 (1H, q, H2 '), 5.93-5.89 (1H, q, H3'), 5.44 (1H, d, H1 '), 5.14 (2H, bs, NH2), 4.23-3.98 (4H, m, H5 ', NHala + CHala), 3.72 (3H, d, OCH2), 3.16 (1H, d, J = 6.03 Hz, H4'), 3.03 (1H, d, CHcPr), 2.86-2.74 ( 1H, m, 1 of H6 '), 1.76-1.66 (1H, m, 1 of H6'), 1.42-1.35 (3H, dd, CH3ala), 0.89-0.83 (2H, q, 2H of CH2cPr), 0.65 -0.60 (2H, t, 2H of CH2cpr). NMR of 13, 174.4 (CO) 161.5 (C2) 160. 3 + 156.6 (p'-Ph), 156.6 (C4), 151.3 (C6) 150.2 ('ipso' -Ph), 136.8 (C2 '), 136.0 (C8), 131.6 (C3'), ¡121.9 (O'-Ph), 115.1 (C5), 69.3 (C5 '), 59.3 (Cl'), '52.9 - '"" - *** (OCH3), 50.6 (CHala), 46.0 (C4'), 34.9 (C6 '), ¡4.2 (CHcPr), 21.3 (CH3ala), 7.8 (CH2cPr). HPLC: tR 31.536 (100%) - (100% water (0 min), 20% water (35 min), 20% water (45 min), 100% water (55 m)). 4-iodophenyl phosphorodichlorurate C6H402P? Cl2I ?. MW = 336.07 This was synthesized by a procedure analogous to that of 4-chlorophenyl phosphorodichlorurate, except that: phosphorus oxychloride (3.29 g, 2 ml, 21.5 mmol), and 4-iodophenol (4.72 g, 21.5 mmol) were used in anhydrous diethyl ether (60 ml) and anhydrous triethylamine (2.71 g, 3 ml, 21.5 mmol) in anhydrous diethyl ether (20 ml) The reaction was stirred at -80 ° C for 4 h and lu | ego at room temperature for 2 h. After filtering and removing the solvent, the product was obtained as a clear liquid (6.2 g, 85.8%). 31 P NMR: 4.72 (s). 1 H NMR: d 7.71 (2H, d, J = 8.59 Hz, O'-Ph), 7.06-7.02 (2H, dd, J = 8.80 Hz, 'm'-Ph), 13 C NMR: 149.9 (' ipso '-Ph), 139.8 (? m'-Ph), 122.9 (O'-Ph), 91.9 (-p'-Ph).

(Metoxy-L-alaninyl) -4-iodophenyl phosphorochloride C? 0H? 2N? O4P? Cl1I ?, MW = 403.55 This was synthesized according to Standard Procedure 3. using the hydrochloride salt of the L-alanine methyl ester ( 1.0 g, 7.16 mmol), 4-iodophenyl phosphorodichloride (2.41 g, 7.16 mmol), triethylamine (2 mL, 14.3 mmol) in DCM (70 mL). The usual treatment provided the gross product! as a yellow oil (3.59 g,> 100%), which was stored with THF (14 ml), providing a 0.51 M solution. 31 P NMR: d 9.31. 9.08 (1: 1). 1 H NMR: 7.74-7.69 (2H, m, O'-Ph), 7.32 | -7.05 (2H, m, * m'-Ph), 4.73 (1H, bs, NHala), 4.20 (IHJ bs, CHala) , 3.81 (3H, d, OCH3), 1.56-1.53 (3H, dd, J = 7.06Hz, CH3ala). 13 C NMR: d 173.4 (CO), 14.9.9 (* ipso'-Ph), 139.5 (* m '-Ph), 123.0 (O'-Ph), 90.4 (p'-Ph), 53.3 (OCH3) , 50.9 (CHala), 20.9 (CH3ala).

O- [4-iodophenyl- (methoxy-L-alaninyl)] -phosphate of (1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1- methanol Cf 1738. C24H2N705P? I1, MW = 653.48 This was synthesized according to Standard Procedure 4. using (ÍS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2- Cyclopentene-1-methanol (100 mg, 0.35 mmol), tBuMgCl (0.7 mL, 0.7 mmol, from a 1.0 M solution in THF) in 1HF (5 mL) and 4-iodophenyl (methoxy-L-alaninyl) -phosphorochloride ( 2.05 ml, 1.05 mmol, of a 0.51 M solution in THF) at room temperature for 48 hours. The solvent was removed under reduced pressure and the residue was treated on a column in 3-6% methanol in chloroform, and then in 3% methanol in chloroform, affording the pure product as a white foamy solid (82.0 mg, 29.9% ). NMR of 3lP: d 3.92 (s). XH NMR: d 7.63-7.59 (2H, dd, J = 8.65 Hz, "m'- Ph) 6.98 (2H, t, J = 8.20 Hz, -Ph) 6.25 1HJ bs, NHcPr), 6.09 (1H, t, H2 '), 5.91 (1H, t, H3'), 5.54 (H, d, H1 '), 5.21 (2H, bs, NH2), 4.35-4.16 (3H, m, i H5 ', NHala; 4.07-3.95 (1H, m, CHala), 3.71 (3H, d, OCH; wing), 3. 15 (1H, d, J = 7.23 Hz, H4 '), 3.03 (1H, bs, CHcPr), 2.85-2.74 (1H, m, 1 of H6'), 1.76-1.65 (1H, m, 1 of H6 ' ), 1.43-1.35 (3H, t, CH3ala), 0.89-0.83 (2H, q, 2H of CH2cPr), 0.63 (2H, bs, 2H of CH2cPr). 13 C NMR: 174.4 (CO) 160.2 (C2), 156.5 (C4), 151.1 (C6) 151.0 ('ipso' -Ph), 139.0 (C2 '), 136.8 (* m' - Ph), 136.0 (C8) ), 131.5 (C3 '), 122.8 (O'-Ph), 115.0 (C5), 88.9 (* p'-Ph), 69.4 (C5'), 59.3 (Cl '), 52.9 (OCH3), 50.6 (CHala) ), 46.0 (C4 '), 34.8 (C6'), 24.2 (CHcPr), 21.3 (CH3ala), 7.8 (CH2cPr). HPLC: tR 33.848 (100%) - (100% water (0 min), 20% water (35 min), 20% water (45 min), 100% water (55 min)).

Ester hydrochloride salt (3-pentyl) of L-alanine Thionyl chloride (1.6 ml, 0.022 H) was added dropwise to a stirred solution of 3-pentanol i (18.2 ml, 0.17 M) at 0 ° C under nitrogen. The mixture was stirred for 30 minutes and then allowed to warm to room temperature. L-alanine (previously dried at 60 ° C over P205 for 4 h: 1.0 g, 0.011 M) was added and the resulting suspension was heated to reflux overnight (the reaction mixture became a clear and colorless solution) . The solvent was removed under reduced pressure, leaving an oil that was repeatedly triturated and co-evaporated with diethyl ether and then oil (60/80) to remove traces of 3-pentanol. The resulting oily residue solidified on drying under high vacuum to yield a peach colored solid (1.96 g, 10 mmol, 89%). dH (d4-CH3OH, 300 MHz) 0.94 (t, 6H, 0-CH (CH2CH3) 2, J = 7), 1.57 (d, 3H, CH3-ala, J = 7) 1, 1.67 (, 4H, 0 -CH (CH2CH3) 2. J = 7), 4.12 (q, 1H, CH-ala, Ji = 7), 4.88 [, 1H, O-CH (C2H2) 2]; dc (d4CH30H, 75 MHz), 8.187 [0-CH (CH2CH3) 2], 15.38 (CH3-ala), 26.39. 26.44] [0- CH (CH2CH3) 2], 48.82 (CH-wing), 79.88 [O-CH (C2H5) 2], 170.03 (0 = 0). (3-phenyloxy-L-alaninyl) phenyl osphorochlorurate Prepared according to the Procedure Normalized 3. from dichlorophosphate :: enyl (0.45 ml, 3.0 mmol), dry triethylamine (0.8 ml, 6.0 mmol), ester hydrochloride salt (3-pentyl) of L-alanine la (0.583 g, 3.0 mmol) and dry DMC (60 ml in total). The crude product was obtained as a light yellow pale oil (1055 g,> 100%). dP (CDC13.121 MHz), 8.99. 9.37. The product was redissolved in sertic THF (5 ml) and 0.211 g / ml was used as a solution.

O- [(S, 4R) -4-r (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol [phenyl (3-pentyloxy-L-alaninyl) phosphate] Cf 16.85] Prepared according to the Procedure Normalized 4. from (ÍS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-met nol (0.2 g, 0.7 mmol), 'BuMgCl (1.0 M in THF, 1.4 ml, 1.4 mmol), phenyl l (3-pentyloxy-L-alaninyl) phosphorochlorurate 1 (3.3 ml of a 0.211 g / ml solution, 2.1 mmol) and dry THF (8 ml). TLC (8% MeOH in CHC13) showed that the reaction had ended after 1.5 hours. The crude residue was purified twice by column chromatography, using (i) MeOH: CHCl (4:96) and (ii) MeOH: CHCl 3 (3:97) as eluent, affording the product as a clear and colorless oil, which solidified in a white foam after trituration and evaporation together with diethyl ether (0.202 g, 0.35 mmol, 50% dP (CDC13, 121 MHz) 3.89, dH (CDCl 3, 300 MHz) 0. 66 (m, 2H, CH2-cPr), 0.90 [, 8H, CH2-cPr and CH (CH2CH3) 2] 1.43 (m, 3H, CH3-ala), 1.58 [, 4H, CH (CH2CH3) 2], 1.72 (m, 1H, 6'Ha), 2.82 (m, 1H, 6'Hb), > 3.05 (m, 1H, CH-cPr), 3.20 (, 1H, 4'H), 3.77 (m, lHj CH-ala), 4.05 (m, 1H, NH-ala), 4.22 (m, 2H, 5 ' H), 4.80 (m, 1H, O-CH-), 4.89 (bs, 2H, NH2), 5.56 (m, 1H, l'H), 5.78 (bs, 1H, NH-cPr), 5.93 (, 1H , 3'H), 6.12 (m, 1H, ¡2'H), 7.26 (m, 5H, ArH), 7.51 (d, 1H, 8H); dc (CDCl3, 75 MHz) 6.37 (CH2-cPr), 8.50 [CH (CH2CH3) 2] 20.28 (CH3-ala), 2.68 (CH-cPr), 25.28. 25.38 [CH (CH2CH3) 2], 33.51. 33.60 (| 6'C), 44.59. 44.69 (4'C), 49.40 (CH-wing), 57.79. 57.83 (LO), 67.90 (5'C), 77.29 (OCH), 113.86 (5C), 119.10-119.18 (o-Ph), 123.84 (p-Ph), 128.61 (m-Ph), 130.09. 130.16 (3'C), 134.46. 134.56 (8C), 135.27. 135.41 (2'C), 149.66-1 ^ 9.93 (6C and ipso-Ph), 155.26 (4C), 158.95 (2C), 172.32. 172.44 (C = 0); m / z (FAB) 584. 2751 (MH +, C28H39N-7O5P requires 584, 2750).

Ester hydrochloride salt (3,3-dimethyl-l-butyl) of L-alanine Prepared according to Standard Procedure 2. from L-alanine (1.6 g, 18 mmol), p-TSA monohydrate (3.8 g, 20 mmol), 3,3-dimethyl-but ^ nl-ol (2.2 ml, 18 mmol ) and toluene (100 ml). Conversion to the hydrochloride salt: The p-toluene sulfonate salt was redissolved in CHCl 3 and washed with 10% potassium carbonate solution and water. The organic layer was dried (MgSO 4), filtered and the solvent was removed under reduced pressure to give the crude product as an oil. Aqueous HCl (1 M) was added and the solution was stirred for 30 minutes at room temperature.] The solution was lyophilized to give the hydrochloride salt as a white solid (3.31 g, 15.8 mmol, 88%). dH (d4-CH3OH, 300 MHz) 0.93 [s, 9H ^ 0- (CH2) 2 (CH3) 3], 1.50 (d, 3H, CH3-ala, J = 7), 1.59 (t, 2H, 0 -CH2CH2, J = 7), 4.05 (q, 1H, CH-ala, J = 1), 4.25 (m, 2H, 0-CH2); dc (d-CH3OH, 75 Hz) 15.18 (CH3-ala), 28.91 [C (CH3) 3], 29.54 [C (CH3) 3], 41.62 (0-CH2CH2-), 48.85 (CHala), 64.11 ( 0-CH2CH2-), 170.03 (C = 0). (3,3-Dimethyl-l-butoxy-L-alaninyl) phenyl phosphorochloridate O II Pho-p- a i Prepared according to Standard Procedure 3. from phenyl dichlorophosphate (0.45 ml, 3.0 mmol), dry triethylamine (0.8 ml, $ .0 mmol), ester hydrochloride salt (3,3-dimethyl-l-butyl) of L -alanine 2a (0.632 g, 3.0 mmol) and dry DCM (60 il in total). The crude product was obtained as a light yellow pale oil (1.038 g, 99%). dP (CDC13.121 MHz) 8.94. 9.30. The product was redissolved in dry THF (5 mL) and used as a 0.208 g / mL solution.

O- [(S, 4 R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-phenyl (3,3-dimethyl-l-butoxy-L-alaninyl) phosphate -metanol [Cf 1687] Prepared according to Standard Procedure 4. from (ÍS, 4R) -4- (2-amiho-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanal (0.2 g, 0.7 mmol), fcBuMgCl (1.0 M in THF: 1.4 ml, 1.4 mmol), (3,3-dimethyl-l-butoxy-L-alaninyl) phenyl phosphorochloride 2b (3.5 ml of a 0.208 g / ml solution, 2.1 mmol) and THF dry (8 ml). TLC (8% MeOH in CHC13) showed that the reaction had ended after 1.5 hours. The crude residue was purified twice by column chromatography, using MeOH: CHCl3 (4:96) as the eluent, affording the product as a clear, colorless oil, which solidified into a white foam after trituration and evaporation together with diethyl ether. (0.287 g, 0.5 mmol, 69%). dP (CDC13.121 MHz) 3.83: dH (CDCl3 .MHZ) 0.66 (m, 2H, CH2-cPr), 0.90 (m, 2H, CH2-cPr), 0.97 's, 9H, C (CH3) 3] 1.41 (m, 3H, CH3-ala), 1.57 (, 2H, O-CH2CH2), 1.74 (m, 1H, 6'Ha), 2.82 (m, 1H, 6'Hb), 3.05 (m, 1H, CH- cPr), 3.20 (m, 1H, 4'H), 3.70 (m, 1H, CH-ala), 4.04 (m, 1H, NH-ala), 4.22 (, 4H, 5'H and 0-CH2CH2), | 4.88 (bs, 2H r, 1 iHn, / l ± 'H a) ¡,, 50..715 1Hn ,, N IH? -ICUGPrJI;) ,, 5.93 (mi, 1' H, 3 '"H), 6.12"(, 1H, 2 '.H), 7_.2-_7 (.m, 5-H, 1 ¡ArH), 7. 52 (d H, 1 IHH, 8 RHH) I; • dc_ í (rCDnrCIi3 .. T75 MHH? ZI) P6, .3 ^ 5R '(rCuH2 --- cPr) 19.96. 20.01 (CH3-wing), 22.69 CH-cPr), 28.52 [C (CH3) 3] 28. 52 [C (CH3) 3], 33.49 33.57 (6'C), 40.59. 40t63 (OCH2CH2-), 44.58. 44.68 (4'C), 49.28 (CH-wing), 57.79. 57.83 (l'C), 62.28. 62.31 (OCH2CH2-), 6_7.86. 67.94 (5'q), 113.81 (5C), 119.10. 119.16 (p-Ph), 123.84 (o-Ph), 128.61 (m-Ph), 1 13300..1100 .. 113300..1166 ((33''CC)), 113344..4477 .. 1134.56 (8C), 135.29. 135.40 (2'C), 149.67-149.75 (6C and ipso-Ph), 155.25 (4C), 158.96 (2C), 172.56. 172.65 (C = 0) m / z (FAB) 598.2896 (MH +, C29H41N705P requires 598.2907) P-Toluenesulfonate salt of the ester (4-methyl-l-pentyl) of L-alanine Prepared according to the Normalized Procedure 2. from L-alanine (1.6 g, 18 mmol), p-TSA monohydrate (3.8 g, 20 mmol), 4-methyl-pentan-l-ol (2.4 ml, 18 mmol ) and toluene (100 ml). The p-toluenesulfonate salt was isolated as a white solid (6.082 g, 17.6 mmol, 98%). dH (d4-CH3OH, 300 MHz) 0.93 [d, 6H, CH (CH3) 2], 1.27 (m, 2H, 0-CH2CH2CH2-), 1.54 (d, 3H, CH3-ala), 1.59 [m, 1H, CH (CH3)] 1.69 [m, 2H, O- (CH2) 2CH2], 2.39 (s,? H, CH3. P-TSA), 4.10 (, 1H, CH-ala), 4.24 (m, 2H ,? | cH2), 7.25 (d, 2H, ArH, p-TSA), 7.72 (d, 2H, ArH, p-TSA); dc (d4-CH3OH, 75 MHz) 15.23 (CH3-ala), 20.31 (CH3-p-TSA), 21.83 [CH (CH3)] J 26.45 (0-CH2CH2CH2-), 27.87 [CH (CH3) 2], 34.93 (0-CH2CH2CH2-), 48.85 (CH-ala), 66.77 [0-CH2 (CH2) 2], 125.93 (o-Ph, p-TSA), 128.83 (m-Ph, p-TSA), 1 40.75 (ipso-C-CH3, p-TSA), 142.39 (ipso-C-S, p-TSA), 1 70.07 (C = 0). (4-Methyl-1-pentyloxy-L-alaninyl) phenyl phosphorochloridate Prepared according to Standard Procedure 3. from phenyllium dichlorophosphate (0.9 ml, 6.0 mmol), dry triethylamine (1.7 ml, 12.0 μmol), ester p-toluenesulfonate salt (4-methyl-l-pentyl) of L -alanine (2.081 g, 6.0 mmol) and dry DCM (100 ml t | otal). The crude product was obtained as a clear, colorless oil (1.79 g, 85%). dP (CDC13.121 MHz) 8.96. 9.31 The product was redissolved in dry THF (10 ml) and 0.179 g / ml was used as a solution.

O- [(1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-phenyl (4-methyl-l-pentyloxy-L-alaninyl) phosphate -metanol [Cf 1721] Prepared according to Standard Procedure 4. from (ÍS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol (0.2 g, 0.7 mmol), üBuMgCl (1.0 M in THF: 1.4 ml, 1.4 mmol), (4-methyl-l-pentyloxy-L-alaninyl) phenyl phosphorochloride 3b (4.1 ml of a 0.179 g / ml solution,? .1 mmol) and dry THF (10 ml). TLC (8% MeOH in CHC13) showed that the reaction had ended after 3 hours. The crude residue was purified by column chromatography using MeOH: CHCl3 (4:96) as the eluent, affording the product as a colorless, clear oil, which solidified in a white foam after trituration and evaporation together with diethyl ether (0.28.8 g, 0.5 mmol, 69%). dP (CDC13.121 MHz) 3.84. 3.88; dH (CDCI3.1 300 MHz) 0.64 (m, 2H, CH2-cPr), 0.87 (m, 2H, CH2-cPr), 1.24 [m, 2H, CH (CH3) 2], 1.40 (t, 3H, CH3-ala), 1.60 [m, 3H, CH (CH3) CH3], 1.73 [m, 3H, CH (CH3) CH3], 2.19 (m, 1H, 6'H,), 2.80 (m, 1H, 6'Hb), 3.03 (m, 1H, CH-cPr), 3.18 (mj, 1H, 4'H), 3.88 (m, 1H , CH-ala), 4.03 (m, 3H, OCH2- and NHala), 4.21 (m, 2H, 5'H), 4.99 (bs, 2H, NH2), 5.55 (m, 1H, l'H), 5.91 (m, 2H, NH-cPr and 3'H), 6.10 (m, 1H, 2'H), 7.29 (, 5H, ArH), 7.51 (d, 1H, 8H), dc (CDC13, 75 MHz) 7.79 (CH2-cPr), 21.55 (CH3-ala), 21.61 [CH (CH3) 2], 23.69 (CH-cPr), 25.66 (0-CH2CH2CH2-), 29.63 [CH (CH3) 2], 35.00 (6 ' C), 38.81 (0-CH2CH2CH2-), 46.01, 46.11 (4'C), 50 t 72 (CH-wing), 59.21 (l'C), 69.31 (5'C), 69.85 (0-CH2CH2-) , 115.25 (5C), 120.52-120.62 (p-Ph), 125.25 (o-Ph), 1.30.04 (m-Ph), 131.59 (3'C), 136.98 (8C), 136.71, 136.79 (2 '). C), 151.08, 151.17 (6C and ipso-Ph), 156.70 (4C), 160.40 L (2Q), 174.00, 174.10 (C = 0); m / z (FAB) 598.2883 (MH +, C29H4iN705P requires 598.2907).

Ester hydrochloride salt (cyclopropyl methyl) of L-alanine Thionyl chloride (1.2 ml, 0.017 ml) was added dropwise to a stirred solution of cyclopropyl methanol (6.8 ml, 8.4 mmol) at 0 ° C under nitrogen. The mixture was stirred for 30 minutes and then allowed to warm to room temperature. L-alanine (previously dried at 60 ° C over P205 for 4 hours: 0.75 g, 8.4 mmol) was added and the resulting suspension was heated to reflux overnight (the reaction mixture became a clear, colorless solution). ). ' The solvent was removed under reduced pressure leaving an orange / red oil which was repeatedly triturated and evaporated together with diethyl ether, to remove traces of cyclopropyl methanol. Diethyl ether (approximately 200 ml) was added and the mixture was stirred for 30 minutes. The resulting suspension was filtered to give the product as a cream solid (1 g, 7.1 mmol, 85%). dH (d4-CH3OH, 300 MHz) 0.38 (m, 2H, CH2-cP3f), 0.65 (m, 2H, CH2-cPr), 1.24 (m, 1H, CH-cPr), 1.60 (d, 3H, CH3 -ala, J = 7), 4.13 (m, 3H, CH-ala and 0-CH2 |); dc (d4-CH3OH, 75 MHz) 4.17 (CH2-cPr), 10.98 (CH-cPr), 16.72 (CH3-ala), 50.33 (CH-ala), 72.70 (0-CH2), 171.56 (C = 0) .

(Cyclopropyl methoxy-L-alaninyl) phosphorochloridate enyl It was prepared according to Standard Procedure 3, from phenyl dichlorophosphate (0.9 ml, 6.0 mmol), dry triethylamine (1.7 ml, 12.0 mmol), ester p-toluenesulfonate salt (cyclopropyl methyl) from L-alanine 4a (1.082 g, 6.0 mmol), and dry DCM (100 ml in total). The crude product was obtained as a light yellow oil (1.79 g, 94%). '-dP (CDC13, 121 MHz) 9.00, 9.36. The product was redissolved in dry THF (51 ml) and used as a 0.385 g / ml solution.

O- [(1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopenten-1-methanol [Cf (cyclopropyl methoxy-L-alaninyl)] phosphate [Cf 1774] It was prepared according to Standard Procedure 4, starting from (ÍS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopenten-l-methanol (0.2 g, 0.7 mmol), cBuMgCl (1.0 M in THF: 1.4 mL, 1.4 mmol) (cyclopropyl methoxy-L-alanyl) phenyl phosphorochloride 4b (1.85 mL of a 0.385 g / mL solution, 2.1 mmol) and THF dry (8 ml). TLC (8% MeOH in CHC13) showed that the reaction had ended after 3.5 hours. The crude residue was purified twice by column chromatography, using MeOH: CHCl3 (4:96) as eluent, affording the product as a clear, colorless oil which solidified in a white foam after trituration and evaporation together with diethyl ether (0.244). g, 0. 4 mmol, 61%). dP (CDC13, 121 MHz) 3.88, 3.94: dH (CDC13, 300 MHz) 0.29 (m, 2H, CH2-cPr), 0.61 (, 2H, CH2-cPr), 0.87 (m, 2H, CH2-cPr), 1.17 (m, 1H, CH-cPr), 1.42 (t, 3H, CH3-ala), 1.69 (m, 1H, 6'Ha), 2.81 (m, 1H, 6'Hb), 3.? (m, 1H, CH-cPr), 3.18 (m, 1H, 4'H), 4.01 (m, 4H, OCH2-, CHala and NH-ala), 4.21 (m, 2H, 5'H), 5.03 ( bs, 2H, 'NH2), 5.56 (m, 1H, l'H), 5.91 (m, 1H, 3'H), 6.05 (bs, 1H, NHcPr), 6.10 (, 1H, 2'H), 7.25 (m, 5H, ArH), 7.51 (d, 1H, 8H); dc (CDC13, 75 MHz) 2.24 (CH2-cPr), 6.33 (CH2-cPp), 8. 66 (CH2-cPr), 20.05, 20.11 (CH3-wing), 22.68 (CH-cPr), 33.55 (6'C), 44.58, 44.68 (4'C), 49.24, 49.31 (CH-wing), 57.77, 57.82 (l'C), 67.76, 67.93 (0-CH2), 69.27, '69.29 (5'C), 113.74 (5C), 119.10-119.19 (p-Ph), 123.84 (o-Ph), 128.61 (m -Ph), 130.09, 130.13 (3'C), 134.42, 134.50 (8C), 136.32, 135.40 (2'C), 149.66, 149.74 (6C and ipso-Ph), 156.26 (4C), 159.00 (2C), 172.64, 172.73 (C = 0) L Ester hydrochloride salt (cyclobutyl-methyl) of L-alanine Prepared according to Standard Procedure 2, from L-alanine (1.6 g, 18 mmol), p-TSA monohydrate (3.8 g, 20 mmol), cyclobutane methanol (1.9 ml, 20 mmol) and toluene (100 ml) . S'al p-toluene sulfonate was isolated as a white solid (4.249 g, 12.9 mmol, 72%). dH (d4-CH3OH, 300 MHz) 1.54 (d, 3H, CH3-ala, J = 7), 1.89 (, 4H, cBu-2 / 4H), 2.08 (m, 2H, cBu-3H), 2.39 (s, 3H, CH3, p-TSA), 2.69 (m, 1H, CH-cBu), 4.11 (q, JH, CH-ala, J = 7), 4.22 (m, 2H, 0-CH2), 7.26 (d, 2H, ArH, p-TSA), 7.73 (d, 2H, ArH, p-TSA); dc (d4-CH3OH, 75 MH, z) 16.7 (CH3-ala), 19.6 (CH2-cBu), 21.7 (CH3-p-TSA), 25.9 (CH2-cBu), 35.7 (CH-cBu), 48.9 (CH-ala), 71.3 (0-CH2), 127.4 (o-Ph, p-TSA), 130.3 (m-Ph, p-TSA), 142.2 (ipso-C-CH3, p-TSA), 143.8 (ipso-CS, p-TSA), 171.6 (C = 0).

(Cyclobutyl methoxy-L-alaninyl) phenyl phosphorochloridate OR II pho-p-a Prepared in accordance with Standard Procedure 3, from phenyl dichlorophosphate (0.9 ml, 6.0 mmol), dry triethylamine (1.7 ml, 12.0 mmol). ester p-toluene sulfonate salt (cyclobutyl methyl) of L-alanine Sa (1.98 g, 6.0 mmol) and dry DCM (100 ml in total). The crude product was obtained as a clear colorless oil (2.04 g, > 100%). dP (CDCI3, 121 MHz) 9.00. 9.34. The product was redissolved in THF (5 ml) and 0.408 g / ml was used as a solution.

O- [(1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-y1) -2-cyclopenten-1-methanol [phenyl (cyclobutyl methoxy-L-alaninyl)] phosphate] Cf 1773] Prepared according to Standard Procedure 4, starting from (ÍS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopenten-1-methanol (0.2 g, 0.7 mmol), fcBuMgCl (1.0 M in THF: 1.4 ml, 1.4 mmol) (cyclobutyl methoxy-L-alaninyl) phenyl phosphorochloride 5b (1.7 ml of a 0.408 g / ml solution, 2.1 'mmol) and dry THF (8 ml) . TLC (8% MeOH in CHC13) showed that the reaction had ended after 3 h. The crude residue was purified twice by column chromatography, using MeOH: CHCl 3 (4:96) as eluent, affording the product as a clear colorless oil, which solidified in a white foam after trituration and coevaporation with diethyl ether (0.213). g, 0. 4 mmol, 52%). dP (CDC13, 121 MHz) 3.87, 3.91; dH (CDC13, 300 MHz) 0.65 (m, 2H, CH2-cPr), 0.89 (, 2H, CH2-cPr), 1.41 (t, 3H, CH3-ala), 1.74 (m, 3H, CH2_cBu and 6'Ha), 2.06 (m , 2H, CH2-cBu), 2.61 (m, 2H, CH2-cBu), 2.81 (m, 1H, 6'Hb), 3.04 (m, 1H, CH-cPr), 3.19 (m, 1H, 4'H ), 3.90 (m, 1H, NH-ala), 4.09 (m, 3H, OCH2-, and CH-ala), 4.22 (m; 2H, 5'H), 4.98 (bs, 2H, NH2), 5.56 ( m, 1H, l'H), 5.92 (m, 2H, 3'H and NH-cPr), 6.11 (m, 1H, 2'H), 7.26 (m, 5H, ArH), 7.52 (d, 1H, 8H); dc (CDC13, 75 MHz) 6.37 (CH2-cP? r), 17.33 (CH2-cBu), 20.17, 20.23 (CH3-ala), 22.68 (CH-lcPr), 23.57 (2 x CH2-cBu), 32.86 ( CH-cBu), 33.51, 33.55 (6'C), 44.58, 44.68 (4'C), 49.23, 49.28 (CH-wing), 57.81, 57.85 (l'C), 67.78-67.94 (5'C) , 68.17, 68.20 (0-CH2), 113.83 (5C), 119.09-119.19 (p-Ph), 123.87 (o-Ph), 128.62 (m-Ph), 130.11, 130.15 (3'C), 134.51 , 134.61 (8C), 135.30, 136.39 (2'C), 149.64-149.97 (6C and ipso-Ph), 155.20 '(4C), 158.87 (2C), 172.64, 172.74 (C = 0). , 'Sal p-toluenesulfonato del ester (ciclopentil-metiloj) of L-alanina HyPTSA i 1 Prepared according to Standard Procedure 2, from L-alanine (1.6 g, 18 mmol), p-TSA monohydrate (3.8 g, 20 mmol), cyclopentane methanol (1.9 ml, 18 mmol) and toluene (100 ml) . The p-toluene sulfonate salt was isolated as a white solid (6.21 g, 18 mmol, 100%). dH (d4-CH3OH, 300 MHz) 1.22 (m, 2H, cPent 2 / 5Ha), 1.46 (d, 3H, CH3-ala), 1.56 (m, 4H, cPent 2/3/4 / 5Hb), 1.70 ( m, 2H, cPent 3 / 4Ha), 2.19 (m, 1H, CH-cPent), 2.31 (s, 3H, CH3, p-TSA), 4.06 (m, 3H, 0-CH2 and CH-ala), 7.18 (d, 2H, ArH, p-TSA), 7.64 (d, 2H, ArH, p-TSA); dc (d4-CH30, 75 MHz) 15.25 (CH3-ala), 20.30 (CH3, p-TSA), 25.27 (CH2-cPent), 29.10, 29.15 (CH2-cPent), 38.72 (CH-cPent), 48.84 ( CH-ala), 70.12 (0-CH2), 126.93 (o-Ph, p-TSA), 128.82 (m-Ph, p-TSA), 140.75 (ipso-C-CH3, p-TSA), 142.40 (ipso -CS, p-TSA), 170.09 (C = 0).

(Cyclopentyl methoxy-L-alaninyl) phenyl phosphorochloridate O II pho-p-a Prepared according to Standard Procedure 3, starting with phenyl dichlorophosphate (0.9 ml, 6.0 mmol), dry triethylamine (1.7 ml, 12.0 mmol), p-toluenesulfonate salt of L-alanine ester 6a (2.069 g, 6.0 mrnol) ) and dry DCM (100 ml in total). The crude product was obtained as a light yellow oil (1197 g> 95%). dP (CDC13, 121 MHz) 8.94, 9.30 The product was redissolved in dry THF (10 iml) and 0.197 g / ml was used as a solution. 0- [Phenyl (cyclopentyl methoxy-L-alaninyl)] phosphate of (SS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2- cyclopentene-1-methanol [Cf 1722] Prepared in accordance with Standard Procedure 2, from L-alanine (IS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopenten-1-methanol (0.2 g, 0.7 mmol), cBuMgCl (1.0 M in THF: 1.4 ml, 1.4 mmol) (cyclopentane methoxy-L-alaninyl) phenyl phosphorochloride 6b (3.7 ml of a 0.197 g / ml solution, 2.1 mmol) and dry THF (10 g. ml). TLC (8% MeOH in CHC13) showed that the reaction had ended after 3 h. The crude residue was purified by column chromatography, using MeOH: CHCl 3 (4:96) as eluent, affording the product as a clear colorless oil, which solidified on a white foam after trituration and coevaporation with diethyl ether (0.314 g, 0.5 mmol, 75%) • dP (CDCl 3, 121 MHz) 3.86, 3.87; dH (CDCI3, 300 MHz) 0.65 (m, 2H, CH2-cPr), 0.89 [m, 8H, CH2-cPr and (CH2) 3-cPent], 1.24 (m, 2H, CH2-cPent), 1.41 (m, 3H, CH3-ala), 1.65 (m, 2H, CH.cPent and 6'Ha), 2.81 (m, 1H , 6'H), 3. 04 (m, 1H, CH-cPr), 3.19 (m, 1H, 4'H), 3.80 (m, 1H, CH-ala), 4.07 (m, 3H, OCH2 and NH-ala), 4.22 (m, 2H, 5'H), 4.92 (bs, 2H, NHa), 5.55 (m, 1H, l'H), 5.81 (bs, 1H, NHcPr), 5.92 (m, 1H, 3'H), 6.11 (m , 1H, 2'H), 7.26 (m, 5H, ArH), 7.52 (d, 1H, 8H); dc (CDC13, 75 MHz) 6.42 (CH2-cPr), 21.43 (CH3-ala), 22.73 (CH-cPr), 24.59 (CH2-cPent), 25.35 (CH2-cPent), 26.64 (CH-cPent), 33.43 , 33.51 (6'C), 44.58, 44.68 (4'C), 49.23 (CH-wing), 57.86, 57.91 (l'C), 64.69, 64.97 (0-CH2-), 67.84 (5'C), 113.74 (5C), 119.09-119.18 (p-Ph), 123.88 (o-Ph), 128.62 (jp-Ph), 130.05, 130.11 (3'C), 134.65, 134.76 (8C), 135.33, 135.44 (? 2 'C), 149.63, 149.72 (6C and ipso-Ph), 154.98 (4C), 158.59 (2C), 172. 50, 172.60 (C = 0); m / z (FAB) 598.2745 (MH +, C? gHsgN-yOsP requires 596.2750). P-Toluenesulfonate salt of the ester (cyclobutyl) of L-alanine Prepared according to Standard Procedure 2, except that benzene was used as solvent: from L-alanine (1.0 g, 11 mmol), p-TSA monohydrate (2.35 g, 12 mmol), cyclobutanoi (0.9 ml, 11 mmol) ) and benzene (65 ml). The p-toluene sulfonate salt was isolated as a white solid (1.73 g, 5.5 mmol, 49%). dH (d4-CH30H, 300 MHz) 1.51 (d, 3H, CH3-wing J = 7), 1.75 (m, 2H, CH2-cBu), 2.14 (m, 2H, CH2-cBu), 2.37 (m, 5H , CH2-cBu and CH3, p-TSA), 4.05 (q, 1H, CH-ala J = 7), 5.08 (m, 1H, CH-cBu), 7.24 (d, 2H, ArH, p-TSA); 7.70 (d, 2H, ArH, p-TSA); dc (d4-CH3OH, 75 MHz) 14.57 (CH2-cBu), 16.58 (CH3-ala), 21.73 (CH3-p-TSA), 31.38, 131.44 (CH2-cBu), 50.16 (CH-ala), 72.47 (CH-cBu), 127.35 (o-Ph, p-TSA), 130.23 (m-Ph, p-TSA), 142.13 pso-C-CH ^, p-TSA), 143.89 (ipso-CS, p-TSA), 170.71 (C = 0).

(Cyclobutoxy-L-alaninyl) phenyl phosphorochloridate OR II PhO-P-CI Prepared according to Standard Procedure 3, starting with phenyl dichlorophosphate (0.75 ml, 5.0 mmol), dry triethylamine (1.4 ml, 10.0 mmol), p-toluenesulfonate salt of L-ailanma ester (cyclopentane methyl) 7a (1.58 g, 5.0 mmol) and dry DCM (65 ml in total). The crude product was obtained as a clear, colorless oil (1.13 g, 71%). dP (CDC13, 121 MHz) 8.96, 9.33 'The product was redissolved in dry THF (51 ml) and 0.226 g / ml was used as a solution.

O- [phenyl (cyclobutoxy-L-alaninyl)] phosphate of (lS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopenten-1-methanol [Cf 1775 ] Prepared according to Procedure I Normalized 4, from (ÍS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopenten-1-methanol (0.2 g, 0.7 mmol), eBuMgCl (1.0 M in THF: 1.4 mL, 1.4 mmol), phenyl (phenyl) methoxy-L-alaninyl) phenyl phosphorochloride 7b (2.95 mL of a 0.226 g / mL solution, 2.1 mmol) and dry THF (8 mL). ). TLC (8% MeOH in CHC13) showed that the reaction had finished after 3.5 hours. The crude residue was purified by column chromatography MeOH: CHCl3 (4:96) as eluent, affording the product as a pale yellow oil which solidified to a cream solid after trituration and evaporation together with diethyl ether (0.238 g, 0.4 mmol, 60%). dP (CDCI3, 121 MHz) 3.89, 3.93; dH (CDCl3, 300 MHz) 0.63 (m, 2H, CH2-cPr), 0.87 (m, 2H, CH2-cPr), 1.39 (m, 3H, CH3-ala), 1.65 (m, 2H, CH2-cBu), 1.81 (m, 1H, 6'Ha), 2.04 (m, 2H, CH2-cBu), 2.36 (m, 2H, CH2-cBu), 2.80 (m, 1H, 6'Hb), 3.03 (m, 1H, CH-cPr), 3.17 (m, 1H, 4'H), 3.97 (m, 2H, NH-ala and CH-ala), 4.18 (m, 2H, 5'H), 4.98 (m, 3H, NH2 and OCH), 5.55 ( m, 1H, l'H), 5.91 (m, 1H, 3'H), 6.01 (, 1H, NH-cPr), 6.10 (m, 1H, 2'H), 7.25 (m, 5H, ArH), 7.51 (d, 1H, 8H); dc (CDCI3, 75 MHz) 7.80 (CH2-cPr), 13.82 (CH2-cBu), 21.42 (CH3-ala), 22.06 (CH-cPr), 30.52-30.63 (CH2-cBu), 35.01 (6'C) , 46.01, 46.12 '(4'C), 50.50 (CH-wing), 59.26 (l'C), 69.30 (CH-cBu),' 70.19 (5'C), 115.25 (5C), 120.53, 120.59 (p. -Ph), 125.28 (o-Ph), 130.05 (m-Ph), 131.53 (3'C), 135.97 (8C), 136.73, 136.85 (2'C), 151.08-151.17 (6C and ipso-Ph), 156.71 (4C), 160.44 (2C), 173.33 (C = 0).

P-toluene sulfonate salt of the cyclopentyl ester of L-alanine Prepared according to Standard Procedure 2, except that benzene was used as solvent: from L-alanine (1.6 g, 18 mmol), p-TSA monohydrate (3.8 g, 20 mmol), cyclopentanol (1.6 ml, 18 mmol) ) and benzene (100 ml). The p-toluene sulfonate salt was isolated as a beige solid (2.81 g, 8.5 mmol, 47%). dH (d4-CH3OH, 300 MHz) 1.51 (d, 3H, CH3-ala, J = 7), 1.71 (m, 6H, CH2-cPnt), 1.92 (m, 2H, CH2-cPnt), 2.39 (m, 5H, CH2-cBu and CH3, p-TSA), 4.04 (q, 1H, CH-ala, J = 7), 5.28 (m, 1H, CH-cPnt), 7.26 (d, 2H, ArH, p-TSA ), 7.73 (d, 2H, ArH, p-TSA); dc (d4-CH3OH, 75 MHz) 16.59 (CH3-ala), 21.72 (CH3-pTSA), 24.97 (CH2-cPnt), 33.81, 33.97 (CH2-cPnt), 50.31 (CH-ala), 81.37 (CH-) cPnt), 127.36 (o-Ph, p-TSA), 130.25 (jn-Ph, p-TSA), 142.20 (ipso-C-CH3, p-TSA), 143.79 (ipso-CS, p-TSA), 171.17 (C = 0) j (Cyclopentyloxy-L-alaninyl) phenyl phosphorochloridate Prepared according to Standard Procedure 3, from fenild dichlorophosphate (0.9 ml, 6.0 mmol), dry triethylamine (1.7 ml, 12.0 mmol), ester p-toluene sulfonate (methyl cyclopentane) salt of L-alanine 8a ( 1.98 g, 6.0 mmol) and dry DCM (100 ml in total). The crude product was obtained as a clear colorless oil (1.8 g, 91%). dP (CDC13, 121 MHz) 9.01, 9.37 The product was redissolved in dry THF (5 ml) and 0.361 g / ml was used as a solution.

O- [(1S, 4R) - (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentyl-l-methanol [Cf 1776] O-[Phenyl (cyclopentoxy-L-alaninyl] phosphate] Prepared according to Standard Procedure 4, starting from (ÍS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopenten-l-methanol (0.2 g, 0.7 mmol), üBuMgCl (1.0 M in THF: 1.4 ml, 1.4 mmol) (cyclobutyl-methoxy-L-alaninyl) phenyl phosphorochloruride 8b (1.93 ml of a 0.361 g / ml solution, 2.1 mmol) and dry THF (8 ml). TLC (8% MeOH in CHC13) showed that the reaction had ended after 3.5 hours. The crude residue was purified twice by column chromatography using MeOH: CHCl 3 (4:96) as the eluent, affording the product as a clear colorless oil I, which solidified in a white foam after trituration and evaporation together with diethyl ether (cf. .J254 g, 0.4 mmol, 62%). dP (CDC13, 121 MHz) 3.97, 3.98; dH (CDC1 | 3, 300 MHz) 0.64 (m, 2H, CH2-cPr), 0.87 (m, 2H, CH2-cPr), 1.38 (m, 3H, CH3-ala), 1.67 (m, 7H, 3 x CH2-cPent and? 6'Ha), 1. 86 (m, 2H, CH2-cPent), 2.81 (m, 1H, 6'Hb), 3.04 Om, 1H, 1 CH-cPr), 3.18 (, 1H, 4'H), 3.96 (m, 2H, NH -ala and CHala), 4.21 (m, 2H, 5'H), 5.02 (bs, 1H, NH2), 6.18 (m, 1H, OCH), 5.56 (m, 1H, l'H), 5.91 (m, 1H, 3'H); 5.98 (bs, 1H, NH-cPr), 6.11 (m, 1H, 2'H), 7.25 (, 5H, ArH), 7.51 (d, 1H, 8H); dc (CDCI3, 75 MHz) 7.78 (CH2-cPr), 21.42, 21.48 (CH3-ala), 24.07 (CH-cPr), 32.91- (CH2-cPent), 33.05, 33.08 (6'C), 34.97, 36.02 (CH2-cPent), 46. 02, 46.12 (4'C), 50.71 (CH-wing), 59.21, 59.25 (l'C), 69.22, 69.29 (5'C), 78.90 (OCH), 115.23 (5C), 120.55-120.61 (p- Ph), 126.28 (o-Ph), 130.05 (m-Ph), 131.53, 131.59 (3'C), 135.87, 135.97 (8C), 136.73, 136.86 (2'C), 151.09, 151.18 (6C and ipso- Ph), 156.71 (4C), 160.44 (2C), 173.71, 173.80 (C = 0).

P-Toluenesulfonate salt of the (phenethyl) ester of L-alanine Prepared according to Standard Procedure 2, from L-alanine (1.0 g, 11 mmol), p-TSA monohydrate (2.35 g, 12 mmol), phenethyl alcohol (1.3 ml, 11 mmol) and toluene (65 ml) . The p-toluene sulfonate salt was isolated as an off-white solid (4.0 g, 10.9 mmol, 97%). dH (d4-CH3OH, 300 MHz) 1.46 (d, 3H, CH3-ala, J = 7), 2.32 (2, 3H, CH3, p-TSA), 2.93 (t, 2H, CH2Ph, J = 7), 4.07 (q, 1H, CH-ala, J = 7), 4.37 (m, 2H, 0-CH2) 7.22 (m, 7H, ArH, p-TSA and PhH), 7.78 (d, 2H, ArH, p- TSA); dc (d4-CH3OH, 75 MHz) 16.80 (CH3-ala), 22.06 (CH3- ^ TSA), 36.20 (CH2-Ph), 50.41 (CH-ala), 68.28 (0-CH2), 127.70, 127.83 (or -Ar and o-Ph, p-TSA), 129.81 (p-Ar), 130.13, 130.48 (m-Ar and m-Ph, p-TSA), 139.23 (ipso-ArC), 142.30 (ipso-C-CH3 , p-TSA), 143.83 (ipso-CS, p-TSA), 171.44 (C = 0).

(Phenetoxy-L-alaninyl) phenyl phosphorochloridate Prepared in accordance with Standard Procedure 3. from phenyl dichlorophosphate (0.5 ml, 3.3 mmol), dry triethylamine (0.93 ml, 6.7 mmol), p-toluene sulfonate salt of the phenethyl ester of L-alanine 9a (1232 g, 3.3 mmol) and dry DCM (60 ml in total). The crude product was obtained as a light I-colorless oil (1.16 g, 94%) i dp (CDCl 3, 121 MHz) 8.93. 9.25 The product was redissolved in THF (5 ml) and 0.233 g / ml was used as a solution.

O- [phenyl (phenetoxy-L-alaninyl) phosphate of (S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol [Cf 1777] Prepared according to Procedure I Normalized 4. from (ÍS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol (0.2 g, 0.7 mmol), fcBuMgCl (1.0 M in THF: 1.4 thousand, 1.4 mmol), (phenetoxy-L-alaninyl) phenyl phosphorochloride 9b (3.3 ml of a 0.233 g / ml solution, 2.1 mmol) and dry THF (8 ml). TLC (S% MeOH in CHC13) showed that the reaction had ended after 3 hours J The crude residue was purified twice by column chromatography, using MeOH: CHCl3 (4:96) as eluent, providing the product as a pale yellow oil that solidified to a cream solid after triturating and evaporating together with diethyl ether (0.181 g, 0.3 mmol, 42%). dp (CDCl 3, 121 MHz) 3.81, 3.86; dH (CDC13 # 300 MHz) 0.65 (m, 2H, CH2-cPr), 0.89 (m, 2H, CH2-cPr), 1.35 (m, 3H, CH3-ala), 1.71 (, 1H, 6'Ha), 2.80 (m, 1H, 6'Hb), 2. 96 (m, 2H, CH2Ph), 3.03 (m, 1H, CH-cPr), 3.17 (, 1H, 4'H), 3.91 (m, 2H, NH-ala and CH-ala), 4.18 (m, 2H , OCH), 4.36 (, 2H, 5'H), 4.99 (bs, 1H, NH2), 5.56 (m, 1H, l'H), 5.92 (m, 2H, 3'H and NH-cPr), 6.09 (m, 1H, 2'H), 7.26 (m, 10H, ArH and PhH), 7.52 (d, 1H, 8H); dc (CDC13, 75 MHz) 6.36 (CH2-cPr), 19.98, 20.04 (CH3-wing), 22.6J5 (CHcPr), 33.46, 33.54 (6'C), 33.90 (CH2-Ph), 44.56, 44.66 (4'C), 49.21 (CH-wing), 57.79, 57.85 (l'C), 64.84 (OCH2), 67.82 (5'C), 113.79 (5C), 119.11- 119.17 (p-Ph), 123.87 (p-Ar), 125.68 (o-Ph), 127.53 (o-Ar), 127.83 (m-Ph), 128.62 (m-Ar), 130.07, 130.14 (3'C), 134.48 (8C), 135.30, 135.39 (2'C), 136.25 (ipso-Ar), 149.63, 149.71 (6C and ipso-Ph), 155.25 (4C), 158.94 (2C), 172.75, 172.45 (C = 0) Salt p-toluene sulfonate ester (3-phenyl-1-propyl) of L-alanine Prepared in accordance with the Procedure 1 Normalized 2, from L-alanine (1.0 g, 11 mmol), p-TSA monohydrate (2.35 g, 12 mmol), 3-phenyl-1-propanol (1.5 ml, 11 mmol) and toluene (65 ml). Removal of the solvent gave the crude product as a yellow oil. Diethyl ether was added and the mixture was cooled for 30 minutes. The resulting suspension was filtered to give the p-toluenesulfonate salt as a white solid (4.24 g, 11.2 mmol, 100%). dH (d4-CH3OH, 300 MHz) 1.53 (d, 3H, CH3-ala, J = 7), 1.97 (m, 2H, CH2CH2Ph), 2.34 (2, 3H, CH3, p-TSA), 2.67 (t, 2H, CH2Ph, J = 7), 4.10 (q, 1H, CH-ala, J = 7), 4.20 (t, 2H, 0-CH2, J = 7), 7.22 (m, 7H, ArH, p-JSA and PhH), 7.75 (d, 2H, ArH, p-TSA); dc (d4-CH3OH, 75 MHz) 16.77 (CH3-ala), 21.93 (CH3-pTSA), 31.63 (CH2CH2-Ph), 33.37 (CH2-Ph), 50.44 (CH-ala), 67.27 (0-CH2 ), 127.26-127.58 (o-Ar and o-Ph, p-TSA), 129.66-130.00 (p-Ar), 130.41 (m-Ar and m-Ph, p-TSA), 142.31 (ipso-ArC), 142.82 (ipso-C-CH3, p-TSA), 143.82 (ipso-CS, p-TSA), 171.47 (C = 0).

(Phenetoxy-L-alaninyl) phenyl phosphorochloridate Prepared in accordance with Standard Procedure 3, starting with phenyl dichlorophosphate! (0.5 ml, 3.3 mmol), dry triethylamine (0.93 ml, 6.7 mmol), ester salt of p-toluene sulfonate (3-phenyl-1-propyl) and L-alanine 9a (1.27 g, 3.3 mmol) and DCM dry (60 ml in total). The crude product was obtained as a light pale brown oil (1.16 g, 90%). dp (CDC13, 121 MHz) 8.94, 9.27 The product was redissolved in dry THF (5 ml) and 0.231 g / ml was used as a solution. ' O- [phenyl (3-phenyl-l-propoxy-L-alaninyl) -osphate) (1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl-2-cyclopentene-1-methanol [Cf.

Prepared according to Standard Procedure 4, starting from (ÍS, 4R) -4- (2-amlno-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol (0.2 g, 0.7 mmol), "BuMgCl (1.0 M in THF: 1.4 mL, 1.4 mmol), (phenyl 3-phenyl-1-propoxy-L-alaninyl) phenyl phosphorochloride 10b (3.5 mL of a 0.231 g / mL solution, 2.1 mmol) and Dry THF (8 ml) TLC (8% MeOH in CHC13) showed that the reaction had ended after 4 h.

The crude residue was purified three times by column chromatography, using MeOH: CHCl 3 (4:96) as eluent, affording the product as a pale yellow oil which solidified into a whitish foam after trituration and evaporation together with diethyl ether (0.330 g. , 0.5 mmol, 75%). dp (CDC13, 121 MHz) 3.89, 3.91; 6H (CDCI3, 300 MHz) 0.63 (, 2H, CH2-cPr)) 0.88 (m, 2H, CH2-cPr), 1.42 (m, 3H, CH3-ala), 1.72 (m, 1H, 6'Ha), 1.98 (CH2CH2Ph), 2. 69 (CH2Ph), 2.80 (, 1H, 6'Hb), 3.04 (, 1H, CH-cPr), 3. 18 (m, 1H, 4'H), 4.07 (m, 6H, NH-ala, CH-ala, OCH and 'H), 5.00 (bs, 1H, NH2), 5.56 (m, 1H, l'H), 5.91 (m, 2H, 3'H and NH-cPr), 6.10 (m, 1H, 2'H), 7.25 (m, 10H, ArH and PbH), 7.52 (d, 1H, 8H); dc (CDCl3, 75 MHz) 6.35 (CH2-cPr), 20.06, 20.12 (CH3-ala), 22.65 (CH-cPr), '29 .02 (CH2CH2Ph), 30.97 (CH2Ph), 33.48, 33.55 (6'C), 44.57, 44. 67 (4'C), 49.26 (CH-wing), 57.78, 57.84 (l'C), 63.84 (OCH2), 67.88 (5'C), 113.83 (5C), 119.10, 119.15 (p-Ph and p-Ar), 123.86 (o-Ph), 125.09 (o-Ar), 127.33, 127.47 (m - Ph), 128.63 (m-Ar), 130.10, 130.17 (3'C), 134.47, 134.58 (8C), 135.27, 135.37 (2'C). 139.81 (ipso-Ar), 149.65, 149. 74 (6C and ipso-Ph), 155.27 (4C), 158.98 (2C), 172.49, 172. 58 (C = 0) P-Toluene sulfanate salt of the (4-phenyl-1-butyl) ester of L-alanine Prepared according to Procedure I Normalized 2, from L-alanine (1.0 g, 11 mmol), p-TSA monohydrate (2.35 g, 12 mmol), 4-phenyl-butanol (1.7 ml, 11 mmol) and toluene (65 ml). Removal of the solvent gave the crude product as a clear colorless laceite which solidified to a white solid after trituration and evaporation together with petroleum (60/80)) (4.4 g, 11.2 mmol, 100%). dH (d4-CH3OH, 300 MHz) 1.55 (d, 3H, CH3-ala, J = 7), 1.74 (m, 4H, - (CH2) 2CH2Ph), 2.41 (2, 3H, CH3, p-TSA), 2.67 (m, 2H, CH2Ph), 4.12 (q, 1H, CH-ala, J = 7), 4.28 (m, 2H, 0-CH2), 7.25 (, 7H, ArH, p-TSA and PhH), 7.75 (d, 2H, ArH, p-TSA); dc (d4-CH3OH, 75 MHz) 16.65 (CH3-ala), 21.74 (CH3-pTSA), 29.18, 29.50 (OCH2 (CH2) -CH2-Ph), 1 36.72 (CH2-Ph), 50.27 (CH-ala ), 67.74 (0-CH2), 127.31, 127.36 (o-Ar and o-Ph, p-TSA), 129.79 (p-Ar), 130.41 (m-Ar and m-Ph, p-TSA), 142.14 ( ipso-ArC), 143.64, 143.87 (ipso-C-CH3 and ipso-CS, p-TSA), 171.47 (C = 0).

(Fenetoxi-L-alaninil) Phenyl phosphorochloridate Prepared according to Standard Procedure 3, starting with phenyl dichlorophosphate (0.5 ml, 3.3 mmol), dry triethylamine (0.93 ml, 6.7 mmol), ester salt of p-toluenesulfonate (4-phenyl-1-butyl) of L-alanine lia (1.32 g, 3.3 mmol) and dry DCM (60 iml in total). The crude product was obtained as a light and pale brown oil (1.13 g, 85%). dP (CDC13, 121 MHz) 8.89, 9.24. The product was redissolved in THF (5 ml) 1 and 0.226 g / ml was used as a solution. ' 0- [(1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2- cyclopentene- [Phenyl (4-phenyl-1-butoxy-L-alaninyl] phosphate] 1-methanol [Cf 1779] Prepared according to the Procedure Normalized 4. from (ÍS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol (0.2 g, 0.7 mmol), ^ uMgCl (1.0 M in THF: 1.4 ml, 1.4 mmol), (phenyl-l-4-phenyl-1-butoxy-L-alaninyl) phosphorochloride of phenyl lb (3.7 ml of a solution of 0.226 g ml, 2.1 mmol) and dry THF (8 ml). TLC (8% MeOH in CHC13) showed that the reaction had ended after 4 hours. The crude residue was purified by column chromatography, using MeOH: CHCl (4:96) as eluent, affording the product as a clear colorless oil which solidified into a white foam after being crushed and evaporated, together with diethyl ether (0.314 g). , 0.5 mmol, 69%). dp (CDC13, 121 MHz) 3.87, 3.90; dH (CDCI3, 300 MHz) 0.65 (m, 2H, CH2-cPr), 0.87 (m, 2H, CH2-cPr), 1.41 (m, 3H, CH3-ala), 1.71 (, 5H, (CH2) 2CH2Ph and 6'Ha), 2.65 (m, 2H, CH2Ph), 2.80 (m, 1H, 6'Hb), 3.04 (m, 1H , CH-cPr), 3.17 (m, 1H, 4'H), 4.06 (m, 6H, NH-ala, CH-ala, ¡5'H and OCH2-) 5.02 (bs, 1H, NH2), 5.56 ( m, 1H, l'H), 5.90 (m, 1H, 3'H), 5.98 (bs, 1H, NH-cPr), 6.10 (m, 1H, 2'H), 7.25 (m, 10H, ArH and PhH), 7.52 (d, 1H, 8H); dc (CDCl3, 75 MHz) 6.35 (CH2-cPr), 20.05, 20.11 (CH3-ala), 22.65 (CH-cPr), 26.51 (CH2CH2CH2Ph), 27.02 (CH2 (CH2) 2Ph), 33.48, 33.55 (6 ' C), 34.32 (CH2Ph), 44.56, 44.67 (4'C), 49.22, 49.26 (CH-wing), 57.79, 57.83 (l'C), 64.40 (OCH2) 67.86, 67.94 (5'C), 113.75 ( 5C), 119.10. 119.15 (p-Ph and p-Ar), 123.85 (o-Ph), 124.88 (o-Ar), 127.33, 127.35 (m-Ph), 128.61 (m-Ar), 130.07, 130.12 (3'C), 134.44, 134.54 (8C), 135.30. 135.39 (2'C), 140.76 (ipso-Ar), 149.64-149.87, (6C and ipso-Ph), 155.26 (4C), 158.98 (2C), 172.53, 172.63 (C = 0).

Salt p-toluene sulfonate ester (2- cyclohexyl ethyl) of L-alanine Prepared according to Standard Procedure 2, from L-alanine (1.0 g, 11 mmol), p-TSA monohydrate (2.35 g, 12 mmol), 2-cyclohexyl ethanol (1.56 ml, 11 mmol) and toluene (65 ml). Removal of the solvent gave the crude product as a clear, colorless oil, which solidified to a white solid after trituration and evaporation together with diethyl ether (2.8 g, 7.5 mmol, 67%). dH (d4-CH3OH, 300 MHz) 0.97 (m, 2H, CH2), 1.24 (m, 4H, 2 x CH2), 1.42 (m, 1H, CH-cHx), 1.54 (d, 3H, CH3-ala, J = 7), 1.63 (m, 2H, CH2), 1.75 (m, 4H, 2 x CH2), 2.39 (s, 3H, CH3, p-TSA), 4.09 (q, 1H, CH-ala, J = 7), 4.28 (one, 2H, 0-CH2), 7.25 (D, 2h, ArH, p-TSA), 7.72 (d, 2H, ArH, p-TSA); dc (d4-CH30H, 75 MHz) 16.65 (CH3-ala), 21.74 (CH3-pTSA), 27.68 (CH2), 27.93 (CH2), 34.58 (CH2), 34.62 I (CH2), 36.10 (CH-cHx) , 50.27 (CH-ala), 66.05 [0-CH2 (CH2) 2], 127.36 (o-Ph, p-TSA), 130.24 (m-Ph, p-TSA), 142.13 (ipso-C-CH3, p -TSA), 143.89 (ipso-CS, p-TSA), 171.49 (C = 0). (2-Cyclohexyl ethoxy-L-alaninyl) phenyl phosphorochloridate i Prepared according to Standard Procedure 3, starting with ethyl dichlorophosphate (0.9 ml, 6.0 mmol), dry triethylamine (1.7 ml, 12.0 mmol), ester p-toluene sulfonate salt (ethyl cyclohexyl) of L-alanine 12a (2.24 g, 6.0 mmol) and dry DCM (100 ml in total). The crude product was obtained as a clear, colorless oil (1.86 g, 83%). dp (CDCl3, 121 MHz) 8.96, 9.31 The product was redissolved in dry THF (5m1) and 0.372 g / ml was used as a solution. 0- [Phenyl (2-cyclohexyl-l-ethoxy-L-alaninyl] phosphate of I (1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl-2-cyclopentene-1) -metanol [Cf 1780] Prepared according to Standard Procedure 4, starting from (ÍS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-l-methanol 0.2 g, 0.7 mmol), tBuMgCl (1.0 M in THF: 1.4 mJ, 1.4 mmol), (phenylhexyl ethoxy-L-alaninyl) phenyl phosphorochloride 12b (2.1 ml of solution 0.372 g / ml, 2.1 mmol) and dry THF (8 ml) . TLC (8% MeOH in CHC13) showed that the reaction had ended after 2.5 hours. The crude residue was purified twice by column chromatography using MeOH: CHCl3 (4:96) as eluent, affording the product as a clear, colorless oil, which solidified to a whitish foam after trituration and evaporation together with diethyl ether (0.302). g, 0.5 mmol, 69%). dp (CDC13, 121 MHz) 3.91, 3.94; dH (CDC13, 300 MHz) 0.64 (m, 2H, CH2-cPr), 0.91 (m, 4H, CH2 and CH2-cPr), 1.2.1 (m, 2H, CH2), 1.41 (, 3H, CH3-wing ), 1.52 (m, 2H, CH-cHx and 6'Ha), 1.70 (m, 6H, 3 x CH2), 2.80 (m, 1H, 6'Hb), 3.04 (m, 1H, CH-cPr), 3.18 (, 1H, 4'H), 4.10 (m, 6H, NH-ala, CH-ala OCH2 and 5'H), 5.03 (bs, 1H, NH2), 5.56 (f '1H, l'H), 5.96 (, 1H, 3'H), 5.98 (m, 1H, NH-cPr), 6.10 (m, 1H, 2'H), 7.25 (m, 5H, Ar), 7.51 (d, 1H, 8H); dc (CDCI3, 75 MHz) 6.35 (CH2-cPr), 20.05, 20.12 (CH3-wing), 22.69 1 (CHcPr), 25.11 (CH2), 25.37 (CH2), 32.04, 32.07 6'C), 33.45, 33.58 (CH-cHx ), 34.76 (CH2), 44.58, 44.69 (4'C), 49.28 (CH-wing), 57.78, 57.83 (l'C), 62.88 (OCH2), 67.86 (5'C), 113.82 (5C), 119.10-119.19 (p-Ph), 123.85 (o-Ph), 128.61 (m-Ph) 130.12 (3'C), 134.44, 134.54 (8C), 135.28, 135.38 (2'C), 149.66-149.94 (6C ipso-Ph), 155.28 (4C), 155.99 (2C), 172.57. 172.66 (C = 0).

Salt p-toluene sulfonate ester (3-cyclohexyl-l-propyl) of L-alanine Prepared according to the Procedure Normalized 2, from L-alanine (1.0 g, 11 mmol), p-TSA monohydrate (2.35 g, 12 mmol), 3-cyclohexyl-1-propanol (1.7 ml, 11 mmol) and toluene (65 ml). The solvent was removed and diethyl ether was added. The resulting suspension was filtered to give the product as a white solid (3.9 g, 10.1 mmol, 90%). dH (d4-CH3OH, 300 MHz) 0.92 (m, 2H, CH2), 1.23 (m, 6H, 3 x CH2), 1.54 (d, 3H, CH3-ala, J = 7), 1.71 (m, 7H, CH-cHx and 3 x CH2), 2.39 (s, 3H, CH3, p-TSA), 4.10 (q, 1H, CH-ala, J = 1), 4.22 (m, 2H, 0-CH2), 7.25 (d, 2H, ArH, p-TSA), 7. 72 (d, 2H, ArH, p-TSA); dc (d4-CH3OH, 75 MHz) 16.66 i (CH3-ala), 21.74 (CH3-pTSA), 27.36 (CH2), 27.83 (CH2), 28. 11 (CH2), 34.80 (CH2), 34.90 (CH2), 39.03 (CH-cHx), 50.27 (CH-ala), 68.27 (OCH2), 127.36 (o-Ph, pj-TSA), 130.24 (m-Ph , p-TSA), 142.12 (ipso-C-CH3, p-TSA), 143.89 (ipso-CS, p-TSA), 171.49 (C = 0). (3-Cycloh-l-propoxy-L-alanyl) phenyl phosphorochloridate Prepared according to Standard Procedure 3, starting with phenyl dichlorophosphate (0.9 ml, 6.0 mmol), dry triethylamine (1.7 ml, 12.0 mmol), ester p-toluene sulfonate salt (3-cycloh-1-propyl) L-alanine 13a (2.32 g, 6.0 mmol) 'and dry DCM (60 ml in total). The crude product was obtained as a light yellow pale oil (2.31 g, 99%). dp (CDC13, 121 MHz) 8.99, 9.35 The crude product was redissolved in dry THF (5 ml) and 0.463 g / ml was used as a solution.

O- [Phenyl (3-cycloh-l-propoxy-L-alaninyl] phosphate] of (1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopenteno- 1-methanol [Cf 1781] Prepared in accordance with Standard Procedure 4, from (ÍS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol (0.2 g, 0.7 mmol), tBuMgCl (1.0 M in THF: 1.4 ml, 1.4 mmol), (3-cycloh-l-propoxy-L-alaninyl) phenyl phosphorochloridate 13b (1.8 ml of 0.463 g / ml solution, 2.1 mmol) and dry THF (8 ml). TLC (8% MeOH in CHC13) showed that the reaction had ended after 2.5 hours. The crude residue was purified by column chromatography, using MeOH: CHCl 3 (4:96) as eluent, affording the product as a clear and colorless ceite, which solidified in a white foam after trituration and evaporation together with diethyl ether ( 0.276 g, 0.4 mmol, 62%). dp (CDC13, 121 MHz) 3.89, 3.91: dH (CDCl3, 300 MHz) 0.64 (m, 2H, CH2-cPr), 0.89 (m, 2H, CH2-cPr), 1.21 (m, 6H, 3 x CH2) , 1.41 (m, 3H, CH3-ala), 1.66 (m, 8H, CH-cHx, 3 x CH2 and 6'Ha), 2.81 (m, 1H, 6'Hb), 3.04 (m, 1H, CH- cPr) 1, 3.18 (m, 1H, 4'H), 4.04 (m, 6H, NH-ala, CH-ala, OCH2 and 5'H), 4.98 (bs, 1H, NH2), 5.56 (m, 1H , l'H), 5.91 (m, 1H, 3'H and NH-cPr), 6.11 (m, 1H, 2'H), 7.26 (m, 5H, Ar), 7.57 (d, 1H, 8H); dc (CDC13, 75 MHz) 6.37 (CH2-cPr), 20.09, 20.15 (CH3-ala), 22.66 (CH-cPr), 24.85 (CH2), 25.27 (CH2), 25.55 (CH2), 29.92 (CH2), 32.20, 32.33 (6'C), 33.49, 33.57 (CH-cHx), 36.22 (CH2), 44.58, 44.68 (4'C), 49.27 (CH-wing), 57.78, 57.83 (l'C), 65.01 (OCH2), 67.84? (5'C), 113.86 (5C), 119.10-119.19 (p-Ph), 123.85 (oPh), 128.61 (m -Ph), 130.12 (3'C), 134.47, 134.57 (8C), 135.28, 135.38 (2'C), 149.65-149.74 (6C ipso-Ph), 155.27 (4C), 158.96 (2C), 172.53, 172.64 (C = 0) Salt p-toluene sulfonate ester (4-cycloh-l-butyl) of L-alanine Prepared according to Standard Procedure 2, starting with L-alanine (0.51 g, 5.8 mmol), p-TSA monohydrate (1.21 g, 6.3 mmol), 4-cycloh-l-butanol (1.0 ml, 5.8 mmol) and toluene (65 ml). The p-toluene sulfonate salt was obtained as a white crystalline solid (2.15 g, 5.4 mmol, 93%). dH (d4-CH3OH, 300 F) 0.92 (m, 2H, CH2), 1.17 (m, 6H, 3 x CH2), 1.39 (, 2H, CH2), 1.54 (d, 3H, CH3-ala, J = 1 ), 1.69 (m, 7H, CH-cHx and 3 x CH2), 2.39 (s, 3H, CH3, p-TSA), 4.10 (q, 1H, CH-ala, J = 1), 4.24 (m, 2H , 0-CH2), 7.25 (d, 2H, ArH, p-TSA), 7.72 (d, 2H, ArH, p-TSA); dc (d4-CH3OH, 75 MHz) 16.66 (CH3-ala), 21.74 (CH3-pTSA), 24.51 (CH2), 27.89 (CH2), 28.18 (CH2), 30.25 (CH2), 34.90 (CH2), 38.59 (CH2), 39.27 (CH-cHx), 50.27 (CH-la), 67.94 (OCH2), 127.36 ( o-Ph, p-TSA), 130.23 (m-Ph p-TSA), 142.15 (ipso-C-CH3, p-TSA), 143.89 (ipso-CS, p-TSA), 171.49 (C = 0) (4-Cycloh-l-butoxy-L-alaninyl) phosphorochloridate, of 1 phenyl i Prepared according to Standard Procedure I, 3 from femlo dichlorophosphate (0.45 ml, 3.0 mmol), dry triethylamine (0.8 ml ^ 6.0 mmol), p-toluene sulfonate salt of ester 14a (12 g, 3.0 mmol) and dry DCM (total 60 ml). The witch product was obtained as a light brown oil (1.36 g, > 100%). dp (CDC13, 121 MHz) 8.91, 9.28 The product was redissolved in dry THF (5 ml) and 0.272 g / ml was used as a solution. 0- [(S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-! Cyclopentene Phenyl (3-cyclohexyl-l-butoxy-L-alaninyl] phosphate; -1-methanol [Cf 1782] Prepared according to Standard Procedure 4, starting from (ÍS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-metyanol 1 (0.2 g, 0.7 mmol), '' BuMgCl (1.0 M in THF: 1.4 mL, 1.4 mmol), (3-cyclohexyl-l-propoxy-L-alaninyl) phenyl phosphorochloride 14b (3.1 mL solution 0.272 g / mL , 2.1 mmol) and dry THF (8 ml). TLC (8% MeOH in CHC13) showed that the reaction had ended after 2.5 h. The crude residue was purified twice by column chromatography using MeOH: CHCl3 (4:96) as the eluent, affording the product as a clear, colorless oil, which solidified into a whitish foam after trituration and evaporation together with diethyl ether (0.341 g). , 0.5 mmol, 75%). dp (CDCI3, 121 MHz) 3.89, 3.91; dH (CDC13, 300 MHz) 0.65 (m, 2H, CH2-cPr)) 0.86 (m, 2H, CH2-cPr), 1.21 (m, 8H, 4 x CH2), 1.41 (m, 3H, CH3-wing) , 1.65 (, 8H, CH-cHx, 3 x CH2 and 6'Ha), 2.81 (, 1H, 6'Hb), 3.04 (m, 1H, CH-cPr), 3.19 (, 1H, 4'H), 4.04 (, 6H, NH-ala, CH-ala, OCH2 and 5'H), 4. 96 (bs, 1H, NH2), 5.56 (m, 1H, l'H), 5.92 (m, 1H, 3'H and NH-cPr), 6.11 (m, 1H, 2'H), 7.26 (, 5H , Ar), 7.52 (d, 1H, 8H); dc (CDCl3, 75 MHz) 6.37 (CH2-cPr), 20.10, 20.16 (CH3-ala), 22.00 (CH2), 22.65 (CH-cPr), 25.34 (CH2), 25.64 (CH2), 27.77 (CH2), 32.28 (CH-cHx), 33.48, 33.56 (6'C), 36.45 (CH2), 44.58, 44.68 (4'C), 49.24 (CH-ála), 57.79, 57.84 (l'C), 64.69 (OCH2), 67.84, 67.94 (5'C) , 113.86 (5C), 119.10-119.19 (p-Ph), 123.86 (o-Ph), 1.28.62 (m-Ph), 130.11, 130.17 (3'C), 134.47, 134.57 (8C), 135.28, 135.39 (2'C), 149.65-149.74 (6C and ipso-Ph), 155.26 (4C), 158.96 (2C), 172.54, 172.64 (C = 0). (Methoxy-L-valinyl) phenyl phosphorochloridate Prepared according to the Procedure Normalized 3, from phenyl dichlorophosphate (0.45 ml, 3.0 mmol), dry triethylamine (0.8 ml, 6.0 I mmol), hydrochloride salt of L-valine I methyl ester (0.5 g, 3.0 mmol) and dry DCM ( 60 ml in total). The crude product was obtained as a colorless oil! Clear (0.922 g,> 100%). dp (CDC13, 121 MHz) 8.99, 9.37 1 The product was redissolved in dry THF (5 'ml) and 0.184 g / ml was used as a solution. 0- [Phenyl (methoxy-L-valinyl] osphate of (SS, 4R) -4- (2-amino-I 6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-l-methanol [Cf 1686 ) ' -.

Prepared according to the Procedure Normalized 4, from (ÍS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol (0.2 g, 0.7 mmol), rBuMgCl (1.0 M in THF: 1.4 mL, 1.4 mmol), phenyl (methoxy valinyl) phosphorochloride I 15a (3.5 ml of solution 0.184 g / ml, 2.1 mmol) and dry THF (5 ml). The reaction mixture was stirred for 16 hours, after which an additional 1.5 ml of the 15a solution was added. The reaction mixture was stirred for another 4 hours. The crude residue was purified by column chromatography, using MeOH: DCM (5:95) 'as eluent, affording the product as a clear colorless oil, which solidified in a white foam after trituration and vaporization together with diethyl ether (0.161 g). , 0.3 mmol, 41%). dp (CDC13, 121 MHz) 4.65, 4.74; dH (CDCI3, 300 MHz) 0.66 1 (m, 2H, CH2-cPr), 0.94 [m, 8H, H2-cPr and CH (CH3) 2], 1.71 (m, 1H, 6'Ha), 2.06 [m, 1H, CH (CH3) 2 ], 2.81 (m, 1H, 6'Hb), 3.04 (m, 1H, CH-cPr), 3.18 (m, 1H, 4'H), 3.52 (m, 1H, CH-val), 3.70 (d, 3H, OCH3), 3.83 (m, 1H, H-val), 4.22 (m, 2H, 5'H), 4.86 (bs, 2H, NH2), 5.56 (m, 1H, l'H), 5.4 (bs , 1H, NH-cPr), 5.93 (m, 1H, 3'H), 6.11 (m, 1H, 2'H), 7.27 (m, 5H, ArH), 7.52 (d, 1H, 8H), dc ( CDC13, 75 MHz) 6.37 (CH2-cPr), 16.36, 16.45 [CH (CH3) 2], 22.65 (CH-cPr), 31.08, 31.16 [CH (CH3) 2], 33.61 (6'C), 44.60, 44.70 (4'C), 51.05, 51.10 (OCH3), 57.78 (l'C), 58.96, 59.01 (CH-val), 67.90 (5'C), 113.91 (5C), 119.03- ^ 19.13 (o-Ph ), 123.80 (p-Ph), 128.58 (mF), 130.05, 130.14 (3'C), 134.47 (8C), 135.27, 135.39 (2'C), 149.66-149.84 (6C and ipso-Ph), 155.28 ( 4C), 158.96 (2C), 172.10, 172.19 (C = 0), m / z (FAB) 556.2428 (MH +, C26H35N7O5P requires 556.2437).

(Methoxy-L-leucinyl) phenyl phosphorochloridate O w pho- p-a 1 NH ?? COJVle Prepared according to standard procedure 3, starting with phenyl dichlorophosphate (0.41 ml, 2.8 mmol), dry triethylamine (0.77 ml, 5.5 mmol), hydrochloride salt of L-leucine methyl ester (0.5 g, 2.8 mmol) and Dry DCM (60 ml in total). The crude product was obtained as a light pale yellow oil (1062 g,> 100%). dp (CDC13, 121 MHz) 9.33, 9.51 The product was redissolved in dry THF (5 ml) and 0.212 g / ml was used as a solution. 0- [Phenyl (methoxy-L-leucinyl] phosphate of (1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol [Cf 1718] Prepared according to the Procedure Normalized 4, from (SS, 4R) -4- (2-amino-6-cyclopropi-lamino-9H-purin-9-yl) -2-cyclopentene-1-methanol (0.2 g, 0.7 mmol), BuMgCl (1.0 M in THF: 1.4 mL, 1.4 mmol), phenyl (methoxy-L-leucinyl) phosphorochloridate 16a (3.2 mL of 0.212 g / mL solution, 2.1 mmol) and dry THF] (10 ml). TLC (8% MeOH in CHC13) showed that the reaction had finished after 2 hours. The crude residue was purified twice by column chromatography, using MeOH: CHCl 3 (4:96) as the present, affording the product as a clear, colorless oil which solidified in a white foam after trituration and evaporation together with diethyl ether (0.211). g, 0.4 mmol, 53%). dp (CDC13, 121 MHz) 3.98, 4.06; dH (CDCl3, 300 MHz) 0.64 (m, 2H, CH2-cPr), 0.89 [m, 8H, CH2-cPr and CH (CH3) 2], 1.51 (m, 2H, CH2-leu), 1.69 [(m, 2H, CH (CH3) 2 and 6'Ha], 2.80 (m, 1H, 6'Hb), 3.04 (, 1H, CH-cPr), 3.16 (m, 1H, 4'H), 3. 67 (m, 1H, CH-leu), 3.69 (d, 3H, OCH3), 3.98 (m, 1H, NH-leu), 4.19 (, 2H, 5'H), 4.97 (bs, 2H, NH2), 5.55 (m, 1H, l'H), 5.91 (m, 1H, NH-cPr and 3'H), 6.09 (m, 1H, 2'H), 7. 25 (m, 5H, ArH), 7.51 (d, 1H, 8H); dc (CDCI3, 75 MHz) 6. 37 (CH2-cPr), 20.69, 20.82 (CH3-leu), 22.69 (CH-cPr), 23. 28, 23.41 [CH (CH3) 2], 33.54 (6'C), 42.60-42.81 (CH2- 1 leu), 44.59. 44.70 (4'C), 51.19, (OCH3), 52.07, 52.16 (CH-Leu), 57.80 (l'C), 67.91, 67.98 (5'C), 113.88, (5C), 118.99-119.14 (or- Ph), 123.80 (p-Ph), 128.58 (m-Ph), 130.06, 130.14 (3'C), 134.53 (8C), 135.27, 135.34 '(2'C), 149.68-149.76 (6C and ipso-Ph ), 155.28 (4C), 158.97 (2C), 173.12, 173.23 (C = 0); m / z (FAB) 570.2610 (MH +, C27 »37N7? 5P requires 570.2594).

(Methoxy-L-prolinyl) phenyl phosphorochloridate Prepared according to the Procedure Normalized 3, from phenyl dichlorophosphate (0.54 ml, 3.6 mmol), dry triethylamine (1.0 ml, 7.2 mmol), hydrochloride salt of L-proline methyl ester (0.6 g, 3.6 mmol) and dry DCM (60 ml in total). The crude product was obtained as a clear, colorless oil (1.24 g,> 100%). dp (CDC13, 121 MHz) 9.02, 9.22 The product was redissolved in dry THF (5 ml) and 0.248 g / ml was used as a solution. 0- [Phenyl (methoxy-L-prolinyl] phosphate of (SS, 4R) -4- (2-a-ino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol [Cf 1719 ) Prepared according to Standard Procedure 4, starting from (ÍS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-anol (0.2 g, 0.7 mmol), tBuMgCl (1.0 M in THF: 1.4 mL, 1.4 mmol), flenyl phosphorochloride (methoxy-L-prolinyl) phosphorochloride 17a (2.6 mL solution 0.248 g / mL, 2.1 mmol) and dry THFl (10 mL). TLC (8% MeOH in CHC13) showed that the reaction had ended after 20 hours. The crude residue was purified twice by column chromatography using MeOH: CHCl 3 (4:96) as eluent, affording the product as a clear, colorless oil which solidified in a white foam after trituration and evaporation together with diethyl ether (0.168 g. , 0.3 mmol, 44%). dp (CDC13, 121 MHz) 2.83, 2.90; dH (CDCl3, 300 MHz) 0.65 (m, 2H, CH2-cPr), 0.90 (m, 2H, CH2-cPr), 1.92 (m, ¡5H, CH2CH2-pro and 6'Ha), 2.83 (m, 1H , 6'Hb), 3.04 (m, 1H, CHcPr), 3.17 (m, 1H, 4'H), 3.45 (m, 2H, N-CH2-pro), 3.70 (d, 3H, OCH3), 4.13 ( m, 1H, CH-pro), 4.30 (m, 2H, 5'H), ^^^^^^^ wgj ^^^^^^^^^^^^^^^^^^^^^^^^ ggj 4.87 (bs, 2H, NH2), 5.56 (m, 1H, l'H), 5.73 (bs, 1H, NHcPr), 5.91 (m, 1H, 3'H), 6.12 (m, 1H, 2'H), 7.27 (m, 5H, ArH), 7.55 (d, 1H, 8H); dc (CDC13, 75 MHz) 6.42 (CH2-cPr), 22.62 (CH-cPr), 23.91, 24.02 (CH2-pro), 30.38, 30.49 (CH2-pro), 33.54 (6'C), 44.61, 44.72 ( 4'C), 46.89 (N-CH2), 51.07, 51.19 (OCH3), 57.71, 57.80 (l'C), 58.84, 58.92 (CH-pro), 67.67, 67.75 (5'C), 113.87 (SC), 118.90-119.22 (or -Ph), 123.64, 123.73 (p-Ph), 128.55, 128.59 (m-Ph), 130.00 (3'C), 134.46 (8C), 135.42, 135.63 (2'C), 149.81, 149.90 (6C and ipso) -Ph), 155.20 (4C), 158.87 (2C), 172. 72, 173.23 (C = 0); m / z (FAB) 554.2283 (MH +, C26H33N7? 5P requires 554.2281).

(Dibenzyloxy-L-aspartinyl) phenyl phosphorochloridate P Prepared according to the Procedure Normalized 3, from phenyl dichlorophosphate (0.45 mL, 3.0 mmol), dry triethylamine (0.8 mL, 6.0 I mmol), p-toluene sulfonate salt of the L-aspartate dibenzyl ester (1.46 g, 3.0 mmol) and dry DMC (60 mL in total). The crude product was obtained as a light yellow oil (0.8024 g, 55%). dp (CDC13, 121 MHz) 9.43, 9.58. The product was redissolved in dry THF (5 ml) and 0.16 g / ml was used as a solution.

O- [Phenyl (dibenzyloxy-L-aspartinyl) phosphate of (lS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol [Cf 1720] Prepared in accordance with Standard Procedure 4, starting from (ÍS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol (0.157 g, 0.55 mmoles), uMgCl (1.0 M in THF: li ml, I 1.1 mmol), phenyl (dibenzyloxy-1-aspartinyl) phosphorochloridate 18a (5.0 ml of a 0.16 g / ml solution, 1.6 mmol) and dry THF (10 ml ). TLC (8% MeOH in CHC13) showed that the reaction had been completed after 1.5 hours. The crude residue was purified twice by column chromatography, using MeOH: CHCl3 (3:97) as eluent, to give the product as a clear, colorless oil, which solidified to give a whitish foam after trituration and coevaporation with diethyl ether (0.284 g, 0.4 mmol, 70%). dp (CDC13, 121 MHz) 3.68, 4.24; dH (CDC13 / 300 MHz) 0.63 (m, 2H, CH2-cPr), 0.85 (m, 2H, CH2-cPr), 1.63 (m, 1H, 6'Ha), 2.71 (m, 1H, 6'Hb) , 3.06 (, 2H, CH-cPr and 4'H), 4.14 (m, 2H, CH-asp, NH-asp), 4.34 (m, 2H, 5'H), 4.98 (bs, 2H, NH2), 5.06 (d, 2H, OCH2Ph), 5.13 (d, 2H, OCH2Ph), 5.53 (m, 1H, l'H), 5.88 (m, 2H, NH-cPr and 3'H), 6.01 (m, 1H, 2'H), 7.25 (, 15H, ArH), 7.49 (d, 1H, 8H), dc (CDCl3, 75 MHz) 6.35 (CH2-cPr), 22.64 (CH-cPr), 33.40 (6'C), 37.44, 37.60 (CH, -asp), 44.50, 44.57 (4'C) 50.20, 50. 33 (CH-asp), 57.79 (l'C), 65.77 (OCH2Ph), 66.65 (OCH2Ph), 67.86, 68.00 (5'C), 113.85 (5C), 119.09-119.34 (o-Ph), 123.92 (p-Ph), 127.34-127.55 (m-Ph and m / p-Bn), 128. 61 (o-Bn), 130.06 (3'C), 134.00 (ipso-Bn), 134.03 (ipso-Bn), 134.61 (8C), 135.23, 135.27 (2'C), 149.47-149.91 (6C and ipso- Ph), 155.28 (4C), 158.95 (2C), 169.22, 169.43, 170.00, 170.29 (C = 0).

O- (phenyl (2-methylpropyl) oxyalaninyl phosphate) of (1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol Cf 1672 This is Prepared by Standard Procedure 4, with a yield of 70%. 'dp 3.87.3.91. dH 0.64 (2H, m, CHaHb, CHa? b »cyclopropyl), 0.92 (8, H, m, CHaHb, CHa-Hb-cyclopropyl, CH (CH3) 2), 1.42 (3H, m, CH3 alaninyl), 1.71 (1H,, 6'-HaHb), 1.92 (1H, m, CH (CH3h) 2), 2.81 (1H, m, 6'-HaHb), 3.03 (1H, m, cyclopropyl CH), 3.19 (1H, m , 4'-H), 3.87 (3H, m, CH alaninyl, CH2CH (CH3) 2), 4.09 (1H,, NH alaninyl), 4.20 (2H, m, 5'-H), 4.91 (2H, br s, NH2), 5.53 (1H, br m, 1'-H), 5.80 (1H, br s, NH-cyclopropyl), 5.92 (1H, m, 3'-H), 6.12 (1H, m, 2'-H), 7.31 (5H, m, Ph-H), 7.48 (1H, br d, 8H). dc 5.45 (CH2-cyclopropyl x 2), 17.01 (CH (CH3) 2), 19.23, 19. 29 (Alanine), 21.74 (CH-cyclopropyl), 25.72 (CH (CH3) 2), 32.58, 32.64 (6'-C), 43.66, 43.76 (4'-C), 48.35 (CH alaninyl), 56.90 (l'-C), 66.88, 66.96, 67.03 (5'-C), 69.57, 69.60 (CH2CH (CH3) 2), 118.17, 118.20, 118. 24, 118.27 (o-Ph, 5-C), 122.94 (p-Ph), 127.70 (m-Ph), 129.19, 129.24 (3'-C), 134.35, 134.45 (8-C, 2'-C) , 148. 81, 148.72 (i-Ph), 149.62, 149.76 (6-C), 154.34 (4-) -fct-.M, C), 158.91, 158.96 (2-C), 171.68, 171.58 (C (0) alaninyl). HPLC tR 33.11 min (0% CH3CN (0 min), 80% CH3CN (35 min), 80% CH3CN (45 min), 0% CH3CN (55 min)).

O- (phenyl (2,2-dimethylpropyl) oxyalaninyl phosphate) of (1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopente or-1-methanol Cf 1673 East was prepared by the Procedure Normalized 4, with a 94% yield. dp 3.88, 3.94. dH 0.61 (2H, m, CHaHb, CHa? b * cyclopropyl), 0.85 (2H, br m, CHaHb, CHa? b 'cyclopropyl), 0.91 (9H, s, C (CH3) 3), 1.41 (3H, m , CH3 alaninyl), 1.70 (1H, m, 6'-HaHb), 2.78 (1H, m, 6'-HaHb), 3.03 (1H,, cyclopropyl CH), 3.18 (1 H, m, 4'-H), 3.81 (3 H, m, CH alaninyl, CH 2 CH (CH 3) z), 4. 09 (1H, m, NH alaninyl), 4.20 (2H, m, 5'-H), 4.97 (2H, br s, NH2), 5.52 (1H, br m, l'-H), 5.86 (1H, br s, NH-cyclopropyl, 3'-H), 6.08 (1H, m, 2'-H), 7.25 (5H, m, Ph-H), 7.48 (1H, br d, 8H). dc 7.89 (CH2-cyclopropyl x 2), 21.74, 21.77 (Melaninyl), 26.81 (C (CH3) 3), 24.21 (CH-cyclopropyl), 31.90 (C (CH3) 3), 35.06 (6'-C) , 46.10, 46.20 (4"-C), 50.79, 50.83 (CH alaninyl), 59.42 (l'-C), 66.35 (5'-C), 69.34, 69.41, 69.49 (CH2C (CH3) 3), 116.41 ( 5-C), 120.62, 120. 66, 120.66, 120.72 (o-Ph), 125.39 (p-Ph), 130.15 (m-Ph), 131.61, 131.65 (3'-C), 136.82, 136.90 (8-C, 2'C), 151.16, 151.25 (6-C, i-Ph), 156.78 (4-C), 158.91, 160.44 (2-C), 174.09, 174.20 (C (O) alaninyl). ES + m / e 584.2640 (MH +, C28H39N7O5P requires 584.2672). HPLC tR 34.97 min (0% CH3CN (or min), 80% CH3CN (35 min), 80% CH3CN (45 min), 0% CH3CN (55 min)).

O- (phenyl (3-methylbutyl) oxyalaninyl phosphate) of (lS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol Cf 1674 This is Prepared by Standard Procedure 4, with a yield of 4.47%. dp 3.87, 3.89: dH 0.57 (2H, m, CHaHb, CHa, Hb-cyclopropyl), 0.80 (8H, m, CHaHb, CHa? b 'cyclopropyl, CH (CH3) 2), 1.30 (3H, m, CH3 alaninyl), 1.42 (2H , m, OCH2CH2), 1.62 (2H, m, 6'-HaHb, CH (CH3) 2), 2.70 (1H, m, 6'-HaHb), 2.92 (1H, br s, CH cyclopropyl), 3.07 (1H,, 4'-H), 3.88 (3H, m, CH alaninyl, OCH2CH2), 4.07 (3H, m, NH alaninyl, 5'-H), 4.91 (2H, br s, NH2), 5.48 (1H, br m, I'-H), 5.83 (2H, br s, NH- cyclopropyl, 3'-H), 6.03 (1H, m, 2'-H), 7.18 (5H, m, Ph-H), 7.42 (1H, br d, 8H). dc 7.81 (CH2-cyclopropyl x 2), 21.49, 21.5.6 (Melaninyl), 22.79, 22.83 (CH (CH3) 2), 24.10 (CH (CH3) 2), 23.58 (CH-cyclopropyl), 34.91, 34.99 (OCH2CH2), 37.54 (6'-C), 46.01, 46.11 (4'-C), 50.70 (CH alaninyl), 59.25, 59.29 (l'-C), 64.63, 64.66 (OCH2CH2), 69.22, 69.30, 69.38 (5'-C), 116.17 (5-C), 120.53, 120.55, 120.59, 120.61 (o-Ph), 125.28 (p-Ph), 130.05 (m-Ph), 131.54, 131.60 (3'-C) , 135.96 (8-C), 136.70, 136.81 (2'-C), 151.09, 151.17 (6-C, i-Ph), 156.68 (4-C), 160.34 (2-C), 173.94, 174.05 (C (O) Alaninyl). ES + m / e 584.2664 (MH +, C28H39N7O5P requires 584.2672). HPLC tR 38.51 min (0% CH3CN (0 min), 80% CH3CN (35 min), 80% CH3CN (45 min), 0% CH3CN (55 min)) O- (phenyl (cycloheptanyl) oxyalaninyl phosphate) of (1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol Cf 1752 This was prepared by Standard Procedure 4 with a yield of 4.41%. dp 3.96. 3.9I dH 0.68 (2H, m, CHaHb, CHa < Hb > cyclopropyl), 0.99 (2H, m, CHaHb, CHa? B 'cyclopropyl) 1.36 (5H, m, CH3 alaninyl, "-HaHb, 6" -HaHb), 1.80 (11H, m, 6'-HaHb, 2"-H, 3" -H, 4"- H, 7" -H, 5"-HaHb, 6" - HaHb), 2.80 (1H, m, 6'-HaHb), 3.12 (1H, brs, CH cyclopropyl), 3.22 (1H, m, 4'-H), 3.97 (2H, m, CH alaninyl, NH alaninyl), 4.20 (2H, m, 5'-H), 4. 95 (1 H, m, O-CH), 5.18 (2 H, br s, NH 2), 5.57 (1 H, br m, 1-H), 5.90 (1 H, m, 3'-H), 6.12 (1 H, m, 2'-H), 6.25 (1H, br s, NH cyclopropyl), 7.25 (5H, m, Ph-H), 7.51 (1H, br d, 8H). dc 15.08 (CH2-cyclopropyl x 2), 28.76, 28.82 (Melaninyl), 30.40, 30.44 (3"-C, 6" -C), 24.10 (CH (CH3) 2), 31.57 (CH-cyclopropyl), 35.87 (4"-C, 5" -C), 41.26, 41.29, 41.31, 41.36 (6'-C), 42.24 (2"-C, 7" -C), 53.32, 53.42 (4'-C), 58.08 (CH alaninyl), 61.15 (l'-C), 66.62 (5'-C), 116.17 (5-C), 127.81, 127.85, 127.88, 127.91 (o- Ph), 132.54 (p-Ph), 137.32, 137.49 (m-Ph), 138.75 (3'-C) , 143.21 (8-C), 144.13, 144.22 (2'-C), 158.40, 158. 49 (6-C, i-Ph), 164.42 (4-C), 167.41 (2-C), 180.47, 180.51, 180.59 (C (O) alaninyl). ES + m / e 632.2719 (M [Na] +, C3oH4oN7? 5NaP requires 632.2726). HPLC tR 41.92 min (0% CH3CN (0 min), 80% CH3CN (35 min), 80% CH3CN (45 min), 0% CH3CN (55 mm)).

• "* - O- (phenyl-diethoxy-phospho-phosphate) of (1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-skypentene-1-methanol Cf 1714 This was prepared by Standard Procedure 4, with a yield of 4.54%, dp 3.76, 4.19 dH 0.62 (2H, m, CHaHb, CHa? b-cyclopropyl), 0.88 (2H, m, CHaHb, CHa? b »cyclopropyl), 1.25 ( 6H, m, CH3-CH2-0 aspartyl x 2), 1.68 (1H, m, 6'-HaHb), 2.75 (2H,, - (C0) -CHaHb aspartyl, 6'-HaHb), 2.97 (2H, m , Cyclopropyl CH, - (CO.}. CHaHb aspartyl), 31.6 (1H, m, 4'-H), 4.15 (8H, m, aspartyl CH, aspartyl CH2-0 x 2, aspartyl NH, 5'-H) 4.90 (2H. Br s, NH2), 5.52 (1H br m, 1H), 5.80 (1H, br s, NH-cyclopropyl), 5.90 (1H, m, 3'-H), 6.08 (1H , m, 2'-H), 7.21 (5H, m, Ph-H), 7.48 (1H br d, 8H), dc 8.65 (CH2-cyclopropyl x 2), 15.31 (CH3-CH2-0 aspartyl x 2) , 24.92 (CH-cyclopropyl), 35.72 ((CO-CH2 aspartyl), 39.74, 39.91 (6'-C), 46.82 (4'-C), 52.41, 52.47 (CH aspartyl), 60.11 (l'-C) , 62.22 (CH3-CH2-0 (CO) CH2 aspartyl), 63.15 (CH3-CH2-0 (CO) CH aspartyl o), 70.14, 70.27, 70.35 (5'-C), 116.12 (5-C), 121.33, 121.40, 121.49, 121.55 (o-Ph), 126.15 (p-Ph), 130.86 (-Ph), 132.36 ( 3'-C), 136.90 (8-C), 137.54 (2'-C), 151.81, 151.85 (6-C, i-Ph), 157.39 (4-C), 161.01 (2-C), 171.67, 171.81 (C (0) aspartyl CH2), 172.38, 172.48, 172.52, 172.62 (C (0) aspartyl). ES + m / e 614.2393 (MH +, C28H37N7O7P requires 614.2492). HPLC tR 30.37 min (0% CH3CN (0 min), 80% CH3CN (35 min), 80% CH3CN (45 min), 0% CH3CN (55 min)).

O- (phenylmethoxymethionyl phosphate) of (1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol Cf 1715 This was prepared by the Normalized Procedure 4, with a yield of 4.49%. dD 3.90, 4.03 dH 0.61 (2H, m, CHaHb, CHa, Hb 'cyclopropyl), 0.86 (2H, m, CHaHb, CHa? B 'cyclopropyl), 1.71 (1H, m, CH-CHaCHb methioninyl), 1.90 (1H, m, CH-CHaCHb methioninyl), 2.01 (3H, d, CH3-S-), 2.30 (1H,, 6'-HaHb), 2.47 (2H, m, '; CH2), 2.78 (1H,, 6'-HaHb), 2.97 (1H, br m, cyclopropyl CH), 3.14 (1H, m, 4'-H), 3.70 (3H, d, CH30-), 3.80 (1H, m, CH methioninyl), 4.17 (3H, m, NH methioninyl, 5'-H), 4.89 (2H, br s, NH2), 5.49 (1H, m, l'-H), 5.80 (1H , br s, NH-cyclopropyl), 5.90 (1H, m, 3'-H), 6.08 (1H, m, 2'-H), 7.24 (5H, m, Ph-H), 7.43 (1H, br d , 8H). dc 6.52 (CH2-cyclopropyl x 2), 14.4, 14.47 (CH3-S-), 22.81 (CH-cyclopropyl), 28.63, 28.78 (S, CH2), '32.62, 32.73, 32.81 (CH-CH2-methioninyl ), 33.65 (6'-C), 44.73, 44.83 (4'-C), 51.67 (CH methioninyl), 57.99 (l-C), 68.13, 68.20, 68.27 (5'-C), 114.03 (5 C) ), 119.15, 119. 22, 119.24, 119.30 (o-Ph), 124.05, 124.10 (p-Ph), 128.80 (m-Ph), 130.26, 130.30 (3 '< C), 134.72 (8-C), 135.42, 135.47 (2 '-C), 149.76, 149.80, 149.84, 149.89 (i-Ph), 150.08 (6-C), 155.38 (4-C), 159.06 (2-C), 172.25, 172.28, 172.32, 172.36 (C (O )). ES + m / e 588.2053 (MH +, C26H34N7O5PS requires 588.2080). HPLC tR 29.64 min (0% CH3CN (0 min), 8-0% CH3CN (35 min), 80% CH3CN (45 min), 0% CH3CN (55 min)).

O- (phenylmethoxytryptophanyl phosphate) of (SS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol Cf 1750 This was prepared by the procedure Normalized 4 with a yield of 4.70%. dp 3.88. 4.01 dH 0.68 (2H m, CHaHb, CHa, Hb 'cyclopropyl), 0.92 (2H, m, CHaHb, CHa? B, cyclopropyl), 1.53 (1H,, 6'-HaHb), 2.68 (1H, m, 6 '-HaHb), 2.99 (2H, br m, cyclopropyl CH, 4'-H), 3.22 (2H, m, CH2-Trp), 3.66 (3H, d, CH3-0-), 3.93 (3H, m, NH Trp, 5'-H), 4.35 (1H, m, CH Trp), 4.94 (2H,! Br s, NH2), 5.49 (1H, m, l'-H), 5.87 (2H, m, NH- cyclopropyl, 3'-H), 5.97 (1H,, 2'-H), 7.01 (1H, m, 6"-H), 7.26 (7H, m, Ph-H4" -H, 5"-H), 7.46 (1H, m, 7"-H), 7.52 (1H, m, 2" -H), 8.63 (1H, br d, 8H), dc 7.81 (CH2-cidopropyl x 2), 24.10 (CH-cyclopropyl) , 34.86, 34.91 (6'-C), 45.81, 45.90, 46.00 (4'C), 52.97 (CH Trp), 59.24, 59.29 (l'-C), 69.14, 69.20 (5'-C), 109.86, 110.11 (3"-C), 111.72 (7" -C), 118.91 (5-C), 119. 95, 120.04 (4"-C, 5" -C), 120.40, 120.47, 120.57,. 120.63 (o-Ph), 122.49, 122.56 (6"-H), 123.70 (2" -C), 125.23, 125.29 (p-Ph), 127.79, 127.98 (9"-C), 130.04 (m-Ph) , 131.27 (3'-C), 136.08 (8-C), 136.50, 136.55, 136.76, 136.87 (2'-C, 8"-C), 151.05, 151.14, 151.17, 151. 26 (i-Ph, 6-C), 156.68 (4-C), 160.35 (2-C), 173.58, 173.66 (C (O)). ES + m / e 643.2432 (MH *, C32H36N8O5P requires 643.2546). HPLC t R 31.46 min (0% CH3CN (0 min), 80% CH3CN (35 min), 80% CH3CN (45 min), 0% CH3CN (55 min)).

O- (phenyl metoxiisoleucinil phosphate) (IS, 4R) -4- (2-amino-6-cyclopropylamino-9 H -purin-9-yl) -2-cyclopentene-1-methanol Cf 1751 This by Procedure Normalized was prepared 4 with a yield of 4.60%. dp 4.48, 4.54 dH 0.68 (2H, m, C Ha Hb, CHa? b 'cyclopropyl), 0.91 (8H, m, Shah, CHa?' cyclopropyl, CH3 x 2 isoleucinyl), 1.15 (1H, CHaCHb isoleucinyl), 1.45 ( 1H, m, CHaCHb isoleucinyl), 1.75 (2H, 6'HaHb, CH3CH), 2.83 (1H, m, 6'HaHb), 3.05 (1H, br m, CH cyclopropyl), 3.19 (1H, m, 4 '-H), 3.62 (1H,, NH isoleucinyl), 3.71 (3H, d, CH3-0-), 3.88 (1H,, CH isoleucinyl), 4.21 (2H,, 5'-H), 4. 91 (2H, br, NH2), 5.55 (1H, m, l'-H), 5.81 (1H, br s, NH-cyclopropyl), 5.93 (1H,, 3'-H), 6.12 (1H, m, 2'-E), 7.28 (5H, m, Ph-H), 7.52 (lH, br d, 8H). dc 7.82 (CH2-cyclopropyl x 2), 11.89 (CH3CH2), 15.72 (CH3CH), 24.08 (CH-cyclopropyl), 25.04, 25.13 (CH3CH2), 34.99 (6'-C), 39.49, 39.56, 39.64 (CH2CH), 46.04, 46.14 (4'-C), 52.46, 52.50 (CH isoleucinyl), 59.24, 59.44, 59.54 (l'-C), 69.34 (5'-C), 116.12 (5-C), 120.47, 120.53, 120.58 (o- Ph), 125.27 (p-Ph), 130.03 (m-Ph), 131.50, 131.57 (3'-C), 136.04 (8'-C), 136.84, 136.74 (2'-C), 151.10, 151.18, 151.27 (i-Ph, 6-C), 156.69 (4- C), 161.06, 161.09, 161.35, 161.41 (2-C), 173.48, 173.53 (C (O) ). ES + m / e 570.2496 (MH +, C27H37N7? 5P requires 570.2594). HPLC tR 32.83, 33.14 min (0% CH3CN (0 min), 80% CH3CN (35 min), 80% CH3CN (45 min), 0% CH3CN (55 min)).

O- (phenyl dimetoxygl tamil phosphate) of (1S, 4R) -4- (2-amino-6-cyclopropylamine-9H-purin-9-yl) -2-cyclopentene-1-methanol Cf 1749 This was prepared by Standard Procedure 4 with a yield of 4.38%. dp 3.99. dH 0.68 (2H, m, CHaHb, CHa'Hb > cyclopropyl), 0.91 (2H, m, CHaHb, CHa'Hb 'cyclopropyl), 1.73 (1H, 6'-HaHb), 2.12 (1H, m, C (O) CH2CHaHb), 2.38 (2H, m, C (0) CH2), 2.82 (1H, m, 6'-HaHb), 3.05 (1H,, cyclopropyl CH), 3.18 (1H, m, 4'-H), 3.68 (3H, s, MeOC (0) CH2), 3.72 (3H, s, MeOC (O) CH), 3.85 (1H, m, NH glutyl), 4.10 (1H, m, CH glutyl ), 4.21 (2H, m, 5'-H), 4.95 (2H, br s, NH2), 5.57 (1H, br m, l'-H), 5.88 (1H, br s, NH-cyclopropyl), 5.95 (1H, m, 3'-H), 6.10 (1H, m, 2'-H), 7.25 (5H, m, Ph-H), 7.54 (1H, br s, 8H). dc 7.82 (CH2-cyclopropyl x 2), 24.12 (CH-cyclopropyl), 29.66, 29.73, 29.88 (C (O) CH2CH2), C (0) CH2CH2), 34.91 (6'-C), 46.02, 46.12 (4 '-C), 52.19 (CH3OC (O) CH2CH2), '54.17, 54.28 (CH3OC (O) CH2), 54.17 (CH glutyl), 59.31 (l'-C), 69.50 (5'-C), 115.42 ( 5-C), 120.48, 120.51, 120.55, 120. 58 (o-Ph), 125.39 (p-Ph), 130.09, 130.22 (-Ph), 131.55, 131.60 (3'-C), 136.13 (8-C), 1136.68, 136.77 (2'-C), 150.98 , 151.05, 151.13 (6-C), 151.76 (i-Ph), 156.65 (4-C), 160.99, 161.02, 161.08, 161.12 (2-C), 173.33, 173.43 (C (O) x 2 glutyl). ES + m / e 600.2216 (MH +, C27H35N707P requires 600.2335). HPLC tR 27.25 min (0% CH3CN (0 min), 80% CH3CN (35 min), 80% CH3CN (45 min), 0% CH3CN (55 min)).

O- (phenyl (methoxy-a-ethylglisinyl phosphate) of (1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol Cf 1783 This is Prepared by the Procedure Normalized 4 with a yield of 4.44%. dp dH 4.10 0.59 (2H, m, C Ha Hb Ha Hb, cyclopropyl), 0.83 (5H, m, C Ha Hb, CHa-Hb- cyclopropyl, CH3-CH2), 1.68 (3H, m, CH3-CH2, 6-Ha) , 2.69 (1H, m, 6'-HaHb), 2.91 (1H, m, 4'-H), 3.06 (1H, m, cyclopropyl CH), 3.58 (3H, d, J 3.0, MeO), 3.90 (2H ,, NH glycinyl, CH glycinyl), 4.07 (2H, m, 5'-H), 5.02 (2H, br s, NH2), 5.42 (1H, m, l'-H), 5.75 (1H,, 3 ' -H), 5.98 (1H, m, 2'-H), 6.03 (1H, m, NH-cyclopropyl), 7.18 (5H, m, Ph-H), 7.41 (1H, br d, 8H). dc 7.76 (CH2-cyclopropyl x 2), 9.68, 9.76 (CH3CH2), 24.12 (CH-cyclopropyl), 28.05 (CH3CH2), 35.01 (6'-C), 46.02. 46.13 (4'-C), 52.70, 52.73 (CH30), 56.02 (l'-C), 59.25 (CH-wing), 69.38 (5'-C), 116.10 (5-C), 120.48, 120.50, 120.55 , 120.57 (o-Ph), 125.27 (p-Ph), 130.04 (m-Ph), 131. 51 (3'-C), 135.86 (8-C), 136.86 (2'-C), 152.08, 151.13, 151.22 (6-C, i-Ph), 156.67 (4-C), 160.40 (2-C) ), 173.84, 173.87, 173.92 (C (O) alaninyl). ES + m / e 564.2094 (M [Na] +, C25H32N 05NaP requires 564.2100). HPLC t R 16.82, 16.84 min (0% CH3CN (0 min), 80% CH3CN (15 min), 80% CH3CN (25 min), 0% CH3CN (35 mm)).

O- (phenyl (methoxy-a-phenyl (RS) glycinyl phosphate) of (1S, 4R) -4- (2-amino-6-c? Clopropylamino-9H-purin-9-yl) -2-cyclopentene-1 -Methanol Cf 1784 This was prepared by Standard Procedure 4 with a yield of 4.46%, dp 3.18, 3.28, 3.42, 4.29.

The proton and carbon NMR provided a complex spectrum, consistent with the racemized product. ES + m / e 612.2086 (M [Na] +, C29H32N7? 5NaP requires 612.2100). HPLC tR 17.63, 18.50 min (0% CH3CN (0 min), 80% CH3CN (15 min), 80% CH3CN (25 min), 0% 'CH3CN (35 min)). (1: 1.08 racemization by HPLC) O- (phenyl (methoxy-a-butylglycinyl phosphate) of (1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol Cf 1786 This is prepared by Standard Procedure 4 with a yield of 4.51%, dp 4.10, 4.16 dH 0.51 (2H,, CHaHb, CHa? b > cyclopropyl), 0.72 (5H, ma, CHaHb, CHa? b, cyclopropyl, CH3-CH2 ), 1.18 (4H, m, CH3-CH2-CH2-), 1.54 (3H, m, CH2-CH2-0, 6'-HaHb), 2.73 (1H, m, 6'-HaHb), 2.93 (1H, m, 4'-H), 3.09 (1H, m, cyclopropyl CH), 3.52 (1H,, CH glycinyl), 3.62 (3H, s, MeO), 3.87 (1H,, NH glycinyl), 4.12 (2H, m , 5'-H), 4.75 (2H, br s, NH2), 5.45 (1H, m, l'-H), 5.79 (2H, br s, NH-cyclopropyl, 3'-H), 6.00 (1H, m, 2'-H), 7.20 (5H, m, Ph-H), 7.42 (1H, br d, 8H), dc 7.76 (CH2-cyclopropyl x 2), 14.23 (CH3CH2), 22.56 (CH3CH2), 24.14 (CH-cyclopropyl), 27.43, 27.50 (CH3CH2CH2), 34.50, 34.58 (CH2CH20), 35.01 (6'-C), 46.02, 46.12 (4'-C), 52.66, 52.68 (CH30), 54.87, 54.94 ( '-C), 59.20 (CH-wing), 69.30, 69.37 (5'-C), 115.18 (5-C), 120.29, 120.42, 120. 50, 120.57 (o-Ph), 125.21 (p-Ph), 130.00 (m-Ph), 131.51, 131.54 (3'-C), 135.86 (8-C), 136.71, 136.76 (2'-C), 151.12, 151.16, 151.20, 151.25 (6-C, i-Ph), 156.73 (4-C), 160.49, 160.96 (2-C), 174.19, 174.26 (C (0) glycinyl). ES + m / e 592.2428 (M [Na] +, C27H36N7? 5NaP requires 592.2413). HPLC t R 18.34, 18.41 min and 16.64 min (6: 1) (0% CH3CN (0 min), 80% CH3CN (35 min), 80% CH3CN (45 min), 0% CH3CN (55 min) ). * Note: the compound was isolated as a stereoisomeric mixture 6: 1 (S: R) at carbon a of the amino acid residue. Additional resonances are indicated in the 31P NMR spectrum at 4.35 and 5.18, which correspond to the diastereomers containing the amino acid residue with the minor configuration (R).

O- (phenyl (methoxy-a-propylglycinyl phosphate) of (lS, 4R) -4- (2-amino-6-cislopropylamino-9H-purin-9-yl) -2-syntelpentene-1-methanol Cf 1785 This is Prepared by Standard Procedure 4 with a yield of 4.50%.

PD 4.14, 4.21. dH 0.62 (2H,, CHaCHb, CHa * Hb »cyclopropyl), 0.86 (5H a, CHaHb, CHa'Hb» cyclopropyl, CH3-CH2), 1.32 (2H, m, CH3-CH2-), 1.63 (3H, m , CH3-CH2, 6'-HaHb), 2.79 (1H, m, 6 '-HaHb), 3.03 (1H, m, 4'H), 3.18 (1H,, cyclopropyl CH), 3.71 (3H, d, J 3.0 MeO), 3.97 (1H,, CH glycinyl), 4.15 (3H, m, 5'-H, NH glycinyl), 5.09 (2H, br s, NH2), 5.55 (1H,, l'-H), 5.90 (1H, m, 3'-H), 6.08 (2H, m, 2'-H, cyclopropyl NH), 7.23 (5H, m, Ph-H), 7.52 (1H, br d, 8H). dc 7.55 (CH2-cyclopropyl x 2), 13.98 (CH3CH2), 18.62, 18.70 (CH3CH2), 24.15 (CH-cyclopropyl), 35.00 (6'-C), 36.89, 36.96 (CH2CH20), 46.02, 46.12 (4 ' -C), 52.68 (CH30), 54.70, 54.77 (l'-C), 59.21 (CH-wing), 69.31, 69.38 (5'C), 115.24 (5-C), 120.45, 120.51, 120.57 (o- Ph), 125.22 (p-Ph), 130.01 (m-Ph), 131.54 (3'-C), 135.89 (8-C), 136.72, 136.78 (2'-C), 151.11, 151.16, 151.20, 151.25 ( 6-C, i-Ph), 156.72 (4-C), 160.45, 160.95 (2-C), 174.18, 174.25 (C (O) alaninyl). ES + m / e 578.2259 (M [Na] *, C26H34N705NaP requires 578.2257). HPLC tR 17.57 min (0% CH3CN (0 min), 80% CH3CN (35 min), 80% CH3CN (45 min), 0% CH3CN (55 min)).

,. £ ". **. O- ((p- (methyl ester of 2", 2" -di ethoxypropionic acid) -phenyl Jmetoxylaninyl phosphate) of (1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) ) -2-cyclopentene-1-methanol Cf 1671 This was prepared by the Procedure Normalized 4 with a yield of 4.24%. dp 3.72, 3.84. dH 0.56 (2H, m, CHaHb, CHa? b. cyclopropyl), 0.79 (2H, m, CHaHb, CHa? b 'cyclopropyl), 1.30 (3H, m, CH alaninyl), 1.63 (1H, m, 6'- HaHb), 2.70 (1H,, 6'-HaHb), 2.95 (1H, br s, 4'-H), 3.07 (3H, m, CH cyclopropyl, Ph-CH2-), 3. 26 (6H, s, (OMe) 2), 3.52 (3H, s, C (OMe) 2COOMe), 3.61 (3H, s, COOMe alaninyl), 3.84-4.08 (4H, m, CH alaninyl, NH alaninyl, 5'-H), 4.99 (2H, br s, NH2), 5.46 (1H, br m, l'-H ), 5.81 (1H, br s, 3'-H), 6.02 (2H,, 3'-H, NH-cyclopropyl), 6.02 (1H,, 2'-H), 7.02 (4H, m, Ph-H) ), 7.45 (1H, br d, 8H). dc 7.77 (CH-cyclopropyl x 2), 21.37 (Melaninyl), 24.01 (CH-cyclopropyl), 34.89 (6'-C), 39.55 (Ph-CH2), 45.97, 46.09 (4'-C), 50.53 (( MeO) 2 CH3OO alamyl), 52. 65 (C (OMe) 2COOMe), 59.28 (l'-C), 69.29 (5'-C), 103.27 (C (OMe) 2), 120.31, 120.38 (o-Ph), 122.94 (p Ph), 131.35 (m-Ph), 131.39 (3'-C), 136.79 (8-C, 2'-C), 150.14, 150.05 (i-Ph 6-C), 152.12 (4-C), 160.24 (2-C) ), 169.08 (C (OMe) 2COOMe), 174.36, 174.46 (C (O) alaninyl).

ES + m / e 696.2531 ([M] +, C3oH4oN7? 9NaP requires 696.2523). HPLC t R 29.02 min (0% CH3CN (0 min), 80% CH3CN (35 min), 80% CH3CN (45 min), 0% CH3CN (55 min)).

O- ((p-methoxyphenyl) me toxylaninyl phosphate) of (1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol Cf 1815 East was prepared by the Procedure Normalized 4 with a yield of 4.23%. dp 4.23, 4.28. dH 0.72 (2H, m, CHaHb, CHa < Hb, cyclopropyl), 1.0 (2H, m, CHaHb, CHa-Hb 'cyclopropyl), 1.48 (3H, m, CH3 alaninyl), 1.82 (1H, m, 6'-HaHb), 2.80 (1H, m, 6' -HaHb), 3.11 (1H, br s, 4'-H), 3.25 (1H, m, cyclopropyl CH), 3.67 (1H, m, NH alaninyl), 3.77 (3H, s, COOMe alaninyl), 3.89 (3H, s, MeO-Ar), 4.14 (1H , m, CH alaninyl), 4.30 (2H, m, 5'-H), 4.94 (2H, br s, NH2), 5.65 (1H, br m, l'-H), 5.83 (1H, br s, NH -cyclopropyl), 6.00 (1H, m, 3'-H), 6.17 (1H, m, 2'-H), 6.92 (2H, m, m-Ar), 7.23 (2H,, o-Ar), 7.63 (1H, s, 8H). dc 7.81 (CH2-cyclopropyl x 2), 21.46, 21.52 (melaninyl), 24.00 (CH-cyclopropyl), 34.96 (6''-C), 46.04, 46.14 (4'-C), 50.64 (CH300 alaninyl), 52.89 (CH-alaninyl), 56.02 (CH30-Ar), 59.28 (l'-C), 69.30 (5'-C), 114.98 (m-Ph 5-C), 121.42, 121.46, 121.52 (o-Ph) , 131.52, 131.56 (3'-C), 135.98, (2'-C), 136.76, 136.87 (i-Ph), 144.61 (8-C), 156.71 (4-C), 157.01 (p-Ar), 161.40, 160.99 (2-C), 174.39, 174.50 (C (O) alaninyl).

HPLC tR 16.28 min (0% CH3CN (0 min), 80% CH3CN (15 min), 80% CH3CN (25 min), 0% CH3CN (35 min)).

O- ((p-propoxyphenyl) methoxylaninyl phosphate) of (1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol Cf 1816 This was prepared by Standard Procedure 4 with a yield of 4.56%. dp 4.33, 4.41. dH 0.62 (2H, m, CHaHb, CHa? b »cyclopropyl), 0.82 (2H, m, CHaHb, CHa, Hb 'cyclopropyl), 1.03 (3H, t, J 6.0, CH3CH2), 1. 39 (3H, m, CH3 alaninyl), 1.66 (1H, m, 6'HaHb), 1.80 (2H, h, J 6.0, CH3-CH2), 2.79 (1H, m, 6'-HaHb, 3.01 (1H, br s, 4'-H), 3.12 (1H, m, cyclopropyl CH), 3.72 (3 , H, s, COOMe alaninyl), 3.89 (2H, t, J 6.0, CH2-0), 4.04 (2H, m, CH alaninyl, NH alaninyl), 4.17 (2H, m, 5'-H), 5.10 (2H, br s, NH2), 5.52 (1H, br m, l'-H), 5.51 (1H, br s, NH-cyclopropyl), 5.89 (1H, m, 3'-H), 6.04 (1H, m, 2'-H), 6.81 (2H, m, m-Ar), 7.11 (2H,, o-Ar), 7.51 (1H, s, 8H). dc 7.77 (CH2-cyclopropyl x 2), 10.91 (CH3-CH2), 21.39, 21.46 (Melaninyl), 22.97 (CH3-CH2), 24.14 (CH-cyclopropyl), 34.96 (6'-C), 46.02, 46.13 (4 '-C),, 50.57, 50.65 (CH300 alaninyl), 52.85, 52.87 (CH-alaninyl), 53.89, 59.25 (l'-C), 69.16, 69.24, 69.33 (5'-C), 70.30 (CH2-O), 115.24, 115.26 (5-C), 115.57 (m-Ph), 121.37, 121.40, 121.43, 121.46 (o-Ph), 131.51, 131.57 (3'-C), 135.93, (2 ' -C), 136.77, 136.85 (i-Ph), 144.47, 144.55 (8-C), 156.54, 156.73 (4-C), 160.45 (p-Ar), 160.91 (2C), 174.48, 174.59 (C (O alaninyl). HPLC tR min (0% CH3CN (0 min), 80% CH3CN (15 min), 80% CH3CN (25 min), 0% CH3CN (35 min)).

O- [4-hydroxyacetophenone- (methoxy-L-alaninyl)] -phosphoramidate of (1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1- methanol Cf 1794 This was prepared by standard procedure 4. The crude residue was purified twice by column chromatography, using MeOH: CHCl 3 (, 3%: 97) and MeOH: EtOAc (5:95) as eluent, to give the title product in the form of a white foam (30 mg, 17 mmol, 15%). d. 3.496. 1 dH 0.66 (, 2H, CH2-cPr), 0.85 (, 2H, CH2-cPr), 1.33 (m, 3H, CH3-CH), 1.7 (, 1H, H'6), 2.53 (s, 3H, CH3 -COPh), 2.8 (m, 1H, H'6), 2.9 (m, 1H, CH-cPr), 3.1 (m, 1H, H'4), 3.6 (s, 3H, CH3-0), 3.9 ( m, 1H, CH3 / CH), 4.1 (m, 2H, | H'5), 4.9 (m, 2H, NH2), 5.5 (m, 1H, H'l), 5.85 (m, 1H, 'H' 3), 6.1 (m, 2H, H'2, NHcPr), 7.2 (dd, 2H, o-Ar), 7.5 (m, 1H, H8), 7.8 (dd, 1H, p-Ar). dc6.371 (CH2cPr), 20 (CH-CH3aa), 21.671 (NHCH3), 25 (CH3CO), 33.458 (C "6), 44.55 (c" 4), 49.5 (CHaa); 51.4 (OCH3), 57.9 (C "l), 67.9 (C" 5), 113.787 (C5), 120 (o-Ar), 122.22 (p-Ar), 128,743 (-Ar), 130 (C "3), 134.53 (C "2), 135.31 (C8), 150.31 (i-Ar), 155.18 (C6), 166.342 (C2), 158.8 (C4), 173.004 (COOCH3), 198 (Co-Ar). HPLC tr 15.976 min (0% CH3CN (0 min), 80% CH3CN (15 min), 80% CH3CN (25 min), 0% CH3CN (35 min)).

O- [4n-butylphenyl- (methoxy-L-alaninyl)] -phosphate from (1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol Cf 1795 The crude residue was purified twice by column chromatography, using MeOH: CHCl3 (3%: 97) and MeOH: CH2Cl2 (5:95) as eluent, to give the title product as a white foam (15 mg, 0.025 mmol, 4%). dp 3.93-4.00 dH 0.66 (m, 2H, CH2-cPr), 0.85 (m, 2H, CH2-cPr), 1.1 (m, 3H, CH3-CH2), 1.2 (m, 4H, CH2-CH2), 1.33 (m, 3H, CH3-CH), 1.7 (m, 1H, H'6), 2.5 (, 2H, CH2-Ar), 2.8 (m, 1H, H'6), 2.9 (m, 1H, CH- cPr), 3.1 (m, 1H, H'4), 3.6 (s, 3H, CH3-O), 3.9 (m, 1H, CH3-CH), 4.1 (m, 2H, H'5), 4.9 (m , 2H, NH2), 5.5 (m, 1H, H * l), 5.85 (m.1H, 3), 6.1 (, 2H, H'2, NHcPr), 7.2 (dd, 2H, o-Ar), 7.5 ( m, 1H, H8), 7.8 (dd, 2H, p-Ar). dc6.371 (CH2cPr), 14.345 (CH3-CH2), 21.49 (CH-CH3aa), 22.66 (CH2-CH3), 21.671 (NHCH3), 30.127 (CH2-CH2-CH2), 33. 458 (C "6), 34,047 (CH2-Ar), 44.55 (C" 4), 49.5 (CHaa), 51.4 (OCH3), 57.9 (C "l), 67.9 (C" 5), 113.787 (C5), 120 (o-Ar), 122.22 (p-Ar), 128,743 (m-Ar), 130 (C "3), 134.53 (C" 2), 135.31 (C8), 146.58 (i-Ar), 155.18 (C6) ), 156.342 (C2), 158.8 (C4), 173.004 (COOCH3) HPLC tr: 19.591 min (0% CH3CN (0 min), 80% CH3CN (15 min), 80% CH3CN (25 min), 0 % CH3CN (35 min)).

O- [Phenylphenyl- (methoxy-L-alaninyl) 1-phosphatide of (1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol Cf 1788 The crude residue was purified three times by column chromatography, using MeOH: CHCl3 (3:97) and MeOH: CH2Cl2 (5:95) and MeOH: AcOEt (3:97) as eluant, to give the product in the form of a yellow foam (35 mg, 0.058 mmol, 8%). dp 3.94-3.96. dH 0.66 (m, 2H, CH2-cPr), 0.85 (m, 2H, CH2-cPr), 1.33 (m, 3H, CH3-CH), 1.7 (m, 1H, H'6), 2.8 (m, 1H, H'6), 2.9 (m, 1H, CH-cPr), 3.25 (m, lHs H'4), 3.6 (s, 3H, CH3-0), 4.1 (m, 1H, CH3-CH), 4.25 (m, 2H, H'5), 4.9 (m, 2H, NH2) ', 5.5 m, 1H, H'l), 5.85 (m, 1H, H'3) ), 6.15 (m, 2H, H'2, NHcPr), 7.35 (m, 9H, Ar), 7.6 (, 1H, H8). dc 6.371 (CH2cPr), 21.49 (CH-CH3aa), 21,671 (NHCH3), 33.458 (C "6), 46.14 (C" 4), 50,671 (CHaa), 52.9 (OCH3), 59.9 (C "l), 65.9 (C "5), 115.787 (C5), 120 (o-Ar), 122.22 (p-Ar), 128,743 (m-Ar), 130 (C" 3), 134.53 (C "2), 135.31 (C8) , 145.25 (i-Ar), 155.18 (C6), 156.342 (C2), 158.8 (C4), 173.004 (COOCH3). HPLC tr: 19.147 min (0% CH3CN (0 min), 80% CH3CN (15 min), 80% CH3CN (25 min), 0% CH3CN (35 min)).

O- [Phenoxyphenyl- (methoxy-L-alaninyl)] -phosphate of (1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol Cf 1787 The crude residue was purified twice by column chromatography, using MeOH: CHCl3 (3:97) and MeOH: CH2Cl2 (5:95) as eluent, to give the title product as a yellow foam (35 mg, 0.058 mmole, 8%). dp 4.212-4.184. dH 0.66 (m, 2H, CH2-cPr), 0.85 (m, 2Hs CH2-cPr), 1.33 (m, 3H, CH3-CH), 1.7 (m, 1H, H'6), 2.8 (, 1H, H '6), 2.9 (m, 1H, CH-cPr), 3.25 (m, 1H, H'4), 3.6 (s, 3H, CH30), 4.1 (m, 1H, CH3-CH), 4.25 (m, 2H, H'5), 4.9 (m, 2H, NH2), 5.5 (m, 1H, H'l), 5.85 (m, 1H, H * 3), 6.15 (m, 2H, 1 H'2, i NHcPr), 7.35 (m, 9H, Ar), 7.6 (m, 1H, H8). dc 6.371 (CH2cPr), 21.49 (CH-CH3aa), 21.671 (NHCH3), 33. 458 (C "6), 46.14 (C" 4), 50,671 (CHaa), 52.9 (OCH3), 59.9 (C "l), 65.9 (C" 5), 115,787 (C5), 120 (o-Ar), 122.22 (p-Ar2), 128,743 (m-Ar), 130 (C "3), 134.53 (C" 2), 135.31 (C8), 153.83 (i-Ar2, m-Ari), 155.18 (C6), 156.3421 (C2), 158.8 (C4), 173.004 (COOCH3). HPLC tr: 18.830 min (0% CH3CN (0 min), 80% CH3CN (15 min), 80% CH3CN (25 min), 0% CH3CN (35 min)).

O- [phenylmethoxy-a, a-cyclopentylglycinyl] phosphate (1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol Cf 1763 This was prepared by Standard Procedure 4, with a yield of 77% . 31P (CDC13) 3.02, 3.09.

XH (CDCl3) 0.56-0.61 (2H, m, CH2 (cpro)), 0.81-0.89 (2H, m, CH2 (cpro)), 1.58-1.78 (5H, m, CCH2CH2CH2CH2C and H'6), 1.87-2.18 (4H, m, CCH2CH2CH2CH2C), 2.64-2.74 (1H, m, H6 '), 2.83-3.09 (2H,, CH (cpro), H4'), 3.60-3.62 (3H, s, OCH3 (wing)), 4.04-4.19 (2H, m, H5 '), 5.20 (2H, bs, NH2), 5.42-5.47 (1H,, H'l), 5.77-5.83 (1H, m, H3 '), 5.98-6.02 (1H,, H2'), 6.20 (NH (cpro)), 7.06-7.27 ( 5H, m, Ar), 7.42-7.48 (1H, s, H8). 13 C (CDCl 3) 8.02 (CH 2 (cpro)), 24.37, 24.41 (CCH 2 CH 2 CH 2 CH 2 C), 34.73 (C 6 '), 38.48, 38.68, 38.79, 38.87 (CCH2CH2CH2CH2C), 46.05, 46.15 (C4 '), 52.99 (OCH3 (wing)), 59.56, 59.60 (Cl'), 67.16 (C (aa), 69.28, 69.37 (C5 '), 114.76 (C5), 120.46, 120.52 (o-Ph), 125.22 (p-Ph), 130.04 (m-Ph), 131.19 (c3 '), 136.72 (C8), 137.13, 137.20 (C2'), 151.27, 151.31, 151.36, 151.40 (C6) , 155.56 (C4), 158. 95 (C2), 175.96, 176.00 (CO).

O- [phenylmethoxy-a, o-cyclohexylglicini] phosphate (ΔS, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol Cf 1764 This was prepared by standard procedure 4 with a yield of 15%. ? (CDCl3) 0.74 (2H, m, CH2 (cpro)), 1.01-1.03 (2H, m, CH2 (cpro)), 1.29-2.23 (11H, m, CCH2CH2CH2CH2CH2C and H6 '), 2.72-2.83 (1H,, H6 '), 3.17 (1H, bs, CH (cpro)), 3.35-3.43 (1H. M, H'), 3.69-3.70 (3H, s, OCH3 (aa)), 4.16-4.29 (2H, m, H5 '), 552-566 (1H, m, Hl'), 5.79 (1H, br s, NH (cpro)), 5.85-5.90 (1H, m, H3 '), 6.08-6.10 (1H, m, H2 '), 7.15-7.35 (5H, m, Ar), 7.37-7.63 (1H, d, H8). T3C (CDC13) 8.30 (CH2 (cpro)), 21.49, 21.68, 21.84, 22.02, 22.11 (CCH2CH2CH2CH2CH2C), 25.14, 25.47, 25.72 (CCH2CH2CH2CH2CH2C), 34.37, 34.59 (C6 '), 46.06, 46.16 (C4'), 52.75, 53.12 (OCH3 (aa)), 59.95, 60.19 (Cl '), 69.22 (C5'), 120.41, 120.47 (o- Ph), 125.22 (p-Ph), 130.04 (-Ph), 130.72, 130.82 (C3 '), 137.41 (C8), 137.56 (C2), 151.33, 151.43 (C6), 175.37 (CO).

O- [(1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol Pf-methoxy-a, cyclopropylglycinyl] phosphate Cf 1762 East was prepared by Standard Procedure 4, with a yield of 69%. XH (CDCl3) 0.68 (2H, m, CH2 (cpro)), 0.90-0.92 (2H, m, CH2 (cpro)), 1.16-1.49 (4H, m, CCH2CH2C (aa)), 1.66-1.72 (1H, m, H6 '), 2.72-2.82 (1H, m, H6'), 3.08-3.15 (2H, m, CH (cpro), H4 '), 3.61-3.63 (3H, d, OCH3 (aa) , 4.24-4.26 (2H,, H5 '), 5.24 (2H, bs, NH2), 5.53 (1H, bs, Hl'), 5.87 (1H, m, H3 '), 6.07 (1H, m, H2'), 6.42-6.45 (1H, bs, NH (cpro)), 7.15-7.35 (5H, m, Ar), 7.56-7.61 (1H, d, H8). 13C (CDC13) 7.92 (CH2 (cpro)), 18.38 (CH2 (aa)), 35.20 (C6 '), 52.88 (OCH3 (aa)), 59.45 (Cl'), 69.32 (C5 '), 120.52 (o- Ph), 125.29 (p-Ph), 130.04 (m-Ph), 137.03 (C2 '), 151.13 (C6), 160.96, 160.98 (C2), 174.35 (CO).

O- [(Methoxycarbonyl) phenylmethoxy-L-alaninyl] phosphate of (1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl); -2-cyclopentene-1-methanol Cf 1766 This was prepared by Standard Procedure 4, with a yield of 37%. XH (CDCl 3) 0.66-0.69 (2H, r 4 CH 2 (cpro)), 0.88-0.94 (2H, m CH 2 (cpro)), 1.38-1.43 (3H, t, CH3 (wing)), 1.70-1.81 (1H,, H6 '), 2.76-2.89 (1H, m, H6'), 3.07 (1H, m CH (cpro)), 3.21 (1H, m, H4 '), 3.71-3.73 (3H, d, OCH3 (wing)), 3.94 (3H, s, COOCH3), 3.98-4.12 (1H, m, CH (wing)), 4.20-4.31 ( 2H, m, H5 '), 5.19 (2H, bs, NH2), 5.54-5.57 (1H,, H1'), 5.91-5.96 (1H,, H3 '), 6.09-6.14 (1H, m, H2') , 6.21 (1H, bs, NH (cpro)), 7.27-7.32 (2H, m, ArO, 2H), 7.53-7.54 (1H, d, H8), 8.02-8.06 (2H, m, COAr, 2H). 13 C (CDCl3) 7.75 (CH2 (cpro)), 21.22, 21.29, 21.46 (CH3 (wing)), 24.16 (NHCH), 34.83 (C6 '), 45.97, 46.07 (C4'), 50.59 (CH (wing) ), 52.57, 59.32 (OCH3 (wing), OCH3 (Ph)), 59.27, 59.32 (Cl '), 69.43 (C5'), 115.07, 115. 11 (C5), 120.28, 120.31, 120.34, 120.38 (o-Ph), 127. 07 (p Ph), 131.58, 131.66 (m-Ph), 131.88 (C3 '), 135. 94, 136.04 (C2 '), 136.61, 136.73 (C8), 151.31, (C6), 156. 52 (C2), 160.97 (C4), 171.57 (CO), 174.30, 174.39 (CO).

O- [p- (trifluoromethylthio) phenylmethoxy-L-alaninyl] phosphate of (1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-l-methanol Cf 1769 This was prepared by Standard Procedure 4, with a yield of 34%. 31 P (CDC13) 3.67, 3? E (CDCl3) 0.81 (2H, bs, CH2 (cpro)), 1.06-1.08 (2H, m, CH2 (cpro)), 1.50-1.54 (3H, t, CH3 (wing )), 1.83-1.93 (1H, m, H6 '), 2.87-2.99 (1H,, H6'), 3.23-3.31 (1H, m, CH (cpro)), 3.82-3.84 (3H, d, OCH3 ( wing)), 4.14-4.15 (1H, m, CH (wing)), 4.32-4.40 (2H, m, H5 '), 5.65 (3H, bs, Hl', NH2), 6.01-6.04 (1H,, H3 '), 6.19-6.23 (1H, m, H2'), 6.64 (1H, bs, NH (cpro)), 7.37-7.43 (2H, m, Ar), 7.67 (1H, d, H8), 7.73-7.76 (2H, m, Ar). T3C (CDCl3) 8.16 (CH2 (cpro)), 21.39, 21.45 (CH3 (wing)), 34.45 (C6 '), 46.09 (C4'), 50.66 (CH (wing)), 53.01 (OCH3 (wing)), 59.87 (Cl '), 69.34 (C5'), 77.47, 77.67 (CF3S?), 121.64, L21.69 (o-Ph), 127.07 (p-Ph), 136.99, 137.14 (C2 ') f 138.56 (C8) , 153.36, 153.45 (C6), 160.93 (C4), 174.27 (CO).

O- [p- (2-methoxyvinyl) phenylmethoxy-L-alaninyl] phosphate from (1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1-methanol Cf 1767 This was prepared by Standard Procedure 4, with a 38% yield . 31P (CDC13) 3.70, 3.74? E (CDCl3) 0.58-0.61 (2H, bs, CH2 (cpro)), 0.81-0.85 (2H, m, CH2 (cpro)), 1.30-1.36 (3H, t, CH3 ( wing)), 1.61-1.72 (1H,, H6 '), 2.33 (3H, s, CH3CO), 2.70-2.79 (1H, m, H6 '), 2.99 (1H, bs, CH (cpro)), 3.13 (1H, bs, H4'), 3.64-3.65 (3H, d, OCH3 (wing)), 3.92-4.01 (1H, m, CH ( to) ) , 4. 11-4.21 (2H,, H5 '), 5.14 (3H, bs, Hl', NH2), 5.47- 5.49 (1H, m, Hl '), 5.82-5.87 (1H, m, H3'), 6.01-6.06 (1H, m, H2 '), 6.12 (1H, bs, NH (cpro)), 6.57-6.63, (1H, dd, CH3COCH = CH), 7.14-7.46 (6H, m, H8, Ar, CH3C0CH =) , 13C (CDCl3) 7.95 (CH2 (cpro)), 21.45 (wing)), 28.02 CCH3CO), 34. 69 (C6), 46.11 (C4 '), 50.64 (CH (wing)), 52.99 JOCH3 (wing)), 59.53 (Cl'), 121.03, 121.10, 121.17 (o-Ph), 127.39 (p-Ph), 130.13 (CH3COCH = CH), 131.44, 131.55 (C3 '), 136.76 (C2'), 142.59 (CH3COCH = CH), 152.72 (C6), 174.26, 174.36 (CO (wing)), 198.70 (COCH3).

O- [p- (2-phenylcarbonylvinyl) phenylmethoxy-L-alaninyl] phosphate of (1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2-cyclopentene-1- methanol Cf 1771 This was prepared by Standard Procedure 4, with a yield of 26%. 31P (CDC13) 3.75, 3.79? E (CDCl3) 0.61-0.66 (2H, m, CH2 (cpro)), 0.85-0.91 (2H, m, CH2 (cpro)), 1.39-1.44 (3H, m, CH3 ( wing)), 1.67-1.86 (1H, m, H6 '), 2.77-2.87 (1H, m, H6'), 3.04-3.05 (1H, bs, CH (pro)), 3.19-3.21 (1H, bs, H4 '), 3.72-3.73 (3H, d, OCH3 (wing)), 4.02-4.13 (1H, m, CH (wing)), 4.19-4.29 (2H, m, H5'), 5.17 (3H bs, Hl ', NH2), 5.53-5.58 (1H, m,, H1'), . 90-5.95 (1H,, H3 '6.09-6.15 (2H, m.H2', NH (cpro)), 7.24-8.08 (12H, m, Ar-, CH = CH, -Ar-, H8). 13C (CDCl3) 7.85 (CH2 (cpro)), 21.35, 21.41, 21.48 (CH3 (wing)), 24.22 (CH (NH)), 34.80 (C6 '), 46.01 (C4'), 50.67 (CH (wing) ), 52.97 (OCH3 (wing)), 59.37 (Cl '), 69.40 (C5), 115.07 (C5), 121.01, 121.07, 121.14 (o-Ph), 128.92, 129.06 (p-Ph), 133.27 (C3' ), 136.13, 136.23 (C2 '), 138.53 (C8), 152.77, 152.86 (C6), 156.31 (C2), 160.97, 160.99 (C4), 174.31. 174.41 (CO (wing)), 1¡90.76 (CO (Ar)).

^ Mditf ^ a ^ O- [p- (2,2-dicyanovinyl) phenylmethoxy-L-alaninyl] phosphate of (S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9 (-il) -2-cyclopentene-l-methanol Cf 1768 This was prepared by Standard Procedure 4, with a yield of 10% .31P (CDC13) 4.54, 4.65.XH (CDCl3) 0.61-0.66 (2H, m, CH2 (cpro) ), 0.85-0.91 (2H, m, CH2 (cpro)), 1.34-1.41 (3H, m, CH3 (wing)), 1.67-1.83 (1H, m, H6 '), 2.77-2.88 (1H, ms H6'), 2.95-2.97 (1H, m, CH (cpro)), 3.23 (1H, bs, H4 '), 3.68-3.70 (3H, d, OCH3 (wing)), 3.99-4.03 (1H, m, CH (wing)), 4.22-4.32 (2H, m, H5 '), 5.49-5.53 (1H, m, H1'), 599-6.03 ( 1H, m, H3 '), 6.16-6.22 (1H, m, H2'), 6.94-6.97 (1H, dd, Ar-CH = CH), 7.36-7.41 (Ar), 7.64-7.65 (1H, d, H8), 7.92-8.16 (Ar). 13 C (CDCl 3) 6.56 (CH 2 (cpro)), 19.85 (CH 3 (ala)), 23.33 (CH (cpro)), 34.23 (C6 '), 46.07 (C4'), 50.47, 50.53 (OCH3 (wing)), 51.78 (CH (wing)), 59.51 (Cl), 69.19, 69.29 (C5 '), 113.84, 114.08 (C5), 121.14, 121.21, 121.27 (o-Ph), 128.49 (p-Ph), 130.74, 130.85 (m-Ph), 132.84 (C3 ') 136.01 (C2'), 136.88, 136.99 (C8) ), 156.47 (C2), 160.99, 161. 03 (C4), 174.27 (CO).

O- [o- (carboxylate ethyl ester) phenylmethoxy-L-alaninyl] phosphate of (1S, 4R) -4- (2-amino-6-cyclopropylamino-9H-purin-9-yl) -2 -ci cl open dye-1-methanol Cf 1798 This was prepared by Standard Procedure 4, with a yield of 24%. 31P (CDC13) 4.03, 4.16 XH (CDCl3) 0.64-0.70 (2H, m, CH2 (cpro)), 0.92-0.93 (2H, d, CH2 (cpro)), 1.38-1.47 (6H,, CH3 (wing) , CH3CH20), 1. 73-1.83 (1H, m, H6 '), 2.78-3.24 (3H, m, H6', H4 ', CH (cycle)), 3.64-3.72 (3H, bs, 0CH3 (wing)), 4.08-4.20 ( 1H, m, CH (wing)), 4.23-4.45 (4H, m, H5 ', CH2CH3), 5.21 (2H, bs, NH2), 5.55-5.60 (1H, m, H1'), 5.89-5.93 (1H , m, H3 '), 6.13-6.18 (1H, m, H2'), 7.23-7.61 (1H, m, H8), 7. 88-7.92 (1H, d, Ar). 13 C (CDCl 3) 7.95 (CH 2 (cpro)), 14.65 (CH 3 CH 2), 21.33, 21.39, 21.68, 21.74 (CH 3 (ala)), 24.30 (NHCH), 34.80 (C6 '), 46.04, 46.14 (C4'), 50.49 (CH (wing)), 52.74, 52.83 (OCH3 (wing)), 59.45 (Cl *), 61.76, 61.82 CH2CH3), 69.43, 69. 51, 69.64 (C5 '), 114.92 (C5), 122.93, 123.09, 123.60, 123.67, 125.26 (Ar), 131.34 (Ar), 131.77, 131.86! (C3'), 134.00 (Ar), 136.48 (C2 ') , 137.05 (C8), 150.20, 150.28 (C6), 155.88 (C2), 160.78, 160.86 (C4), 174.28, 174.28, 174.39, 174.55, 174.65 (CO).

Example A Guanine-5 '- [phenyl- (methoxy-L-alaninyl)] -phosphate of (IR, 4S) -9- [4- (hydroxymethyl) 2-cyclopentene-2-yl] C2? H25? 6 6P? , MW = 488.45. g ^^ E ^^^^ fc R. Vince and M. Hua, J. Med. Chem. 1999, 33, 17-21, which is incorporated herein by reference, describe a procedure for the synthesis of (IR, 4S) -9- (4- (hydroxymethyl) -2-cyclopentene-2-yl) guanine. Dry (IR, 4S) -9- [4- (hydroxymethyl) -2-cyclopentene-2-yl) guanine (400 mg, 1.618 mmol) by azeotropic distillation with anhydrous pyridine (4 x 10 ml), maintained under nitrogen gas and was suspended in anhydrous THF (30 ml). TBuMgCl (1.0 M solution in THF) (1.6 ml, 1.618 mmol) was added dropwise and the resulting dark suspension was stirred vigorously for 10 minutes. Phosphorochloridate (4.79 ml, 2.43 mmol) was added dropwise and the reaction mixture was stirred at room temperature for 69 hours. After this time, the suspended solid was partially in solution although solid was still observed in the walls of the flask. Added more phosphoroclorurate (4.79 ml, 2.43 mmol) and the reaction mixture was stirred for another 55 hours before quenching the reaction by the addition of saturated solution of NH 4 Cl (0.25M). After stirring for another 10 minutes, the solvent was removed under reduced pressure to give the crude product as a yellow gum which was solubilized in MeOH, dried over MgSO4 (s), filtered and the filtrate was reduced to dryness. The residue was solubilized in MeOH, silica was added and then the solvent was removed to give the product preabsorbed on silica, which was loaded on a silica column and eluted with 8% MeOH in CHC13. The product was then purified by gradient elution from 5 to 9 MeOH in DCM on a Biotage flash column, and after 1 d evaporating the appropriate fractions, the product was obtained as a white foam (70 mg, 8.6%). The compound had a formula 31 P NMR (MeOH-d4): d 5.18, 4.86 (1: 1). NMR of XH: d 7.67 (1H), 7.73-7.30 (2H), 7.21-7.14 (3H), 6.17-6.10 (1H), 5.97-5.94 (1H), 5.53, -5.48 (1H), 4.28-4.15 ( 2H), 4.00-3.87 (1H), 3.66 (3H), 3.18 (1H), 2.83-2.71 (1H), 1.82-166 (1H), 1.36-1.29 (3H). 13P NMR: d 174.4 *, 158.5, 154.1, 151.7, 151.1 *, 136.9 *, 136.5, 130.7, 129.7, 125.0, 120.4 *, 16.8, 68.9 *, 59.8, 51.7, 50.5 *, 46.0 *, 34.2, 19.3 * .

MS ES +: m / z 488.86 (100%) (M) +, 500.04 (12%) (M + NA) +, 507.96 (25%) (M + K) +. MS FAB: calculated m / z 489.165146, found m / z 489.164677.

In vitro assay Cells were infected with HIV-1 as previously described [Balzarini et al AIDS (1991 '), 5_, 21-28]. Briefly, 5 x 105 cells per milliliter were infected with HIV-1 or HIV-2 at 100 CCID50 (infectious dose of the 50% cell culture) per milliliter of cell suspension. Next, 100 μl of the infected cell suspension was transferred to wells of a microtiter plate and mixed with 100 μl of the appropriate dilutions of the test compounds. After 4 days, the formation of giant cells in HIV-infected cell cultures [CEM] was recorded under a microscope. The 50% effective concentration (EC5o) and the 50% cytotoxic concentration (CC5! O) were defined as the compound concentrations needed to reduce the number of giant cells or viable cells in cell cultures infected by viruses to 50%. infected simulated, respectively.

In the following tables, the data columns are, in order: HIV 1 CEM: EC50 in μM for the inhibition of HIV-1 in CEM HIV 2 CEM cells: EC50 in μM for the inhibition of HIV-2 in CEM CC50 CEM cells : CC50 in μM for toxicity to CEM cells. Table I below contains the in vi tro data comparing the biological activity of the compound cf 1490 with its non-phosphoramidated counterpart, Abacavir, and with the compound of Comparative Example A and its non-phosphoramidated counterpart. Abacavir is normally used in the treatment of patients with HIV infection. Table I As can be seen in Table 1, compound cf 1490, which is an embodiment of the present invention, has a much improved pharmacological potency (27 to 33 times) with respect to HIV in vi tro than 7Abacavir, which is not known phosphoramidated. The increase in the improvement of Table 1 is the average increase in the potency of the compound phosphoramidate against its nucleoside promoter for HIV 1 and HIV 2. The surprising nature of this result is demonstrated with respect to Comparative Example A and its non-phosphoramidated counterpart . The structure of the non-phosphoramidated homolog of Example A is, in appearance, very similar to that of Abacavir. The phosphoramidate of Example A, however, shows a potency with respect to HIV that is only comparable to that of its non-phosphoramidated counterpart, whose structural formula is: The following Table II compares the power data in vi tro of Compound 1490 with equivalent known data described in PCT / GB96 / O0580 for known phosphoramidated compounds. The data in each case were obtained by the in vi tro test described above under the heading "Test in vi tro" Table II Each of compounds 951, 1078 and 1093 is a phosphoramidate of a nucleoside analogue. Compound 951 is 5 '- (phenyl-ethoxyalaninyl) phosphoramidate of 2', 3 '-dideoxy-2', 3 '-didehydrotimidine. Compound 1078 is 5'- (phenyl-dimethoxyapartyl) phosphoramidate 2 ', 3'-dideoxy-2', 3'-didehydrotimidine.

Compound 1093 is 5 '- (phenylmethoxyalaninyl) phosphoramidate 2', 3'-dideoxy-adenosine. As can be seen from Table II, compound 1490 demonstrates a high degree of pharmacological potency with respect to HIV. Table III presents the power and toxicity data in a larger range of compounds, in which: Cpd and Init refer to the reference numbers of the compounds, X refers to the aryl radical (phosphate); And it refers to the group: Z refers to the bond in the five-membered sugar ring: = it is unsaturated pentene; H is saturated. B in each case is "1592", which refers to the base present in Abacavir. , The columns of data are, in order: HIV 1 CEM: EC5o in μM for the inhibition of HIV-1 in CEM HIV 2 CEM cells: EC50 in μM for the inhibition of HIV-2 in CEM HIV 2 CEM.TK cells: EC50 in μM for the inhibition of HIV-2 in CEM / TK CC50 CEM cells: CC5o in μM for toxicity towards CEM EC50 cells MSV: EC50 in μM for the inhibition of MSV MCC MSV: minimum cytotoxic concentration in the MSV assay.

Table III Stability to acids The compounds were tested for their stability towards decomposition by acid-induced hydrolysis using an assay designed to simulate stomach conditions. Each compound was incubated in diluted HCl of pH 1 for 24 hours at 25 ° C. 0.3 mg of compound was added to 1 ml of HCl 0. IN at 25 ° C. HPLC was performed immediately at time = 0 and at intervals up to about 24 hours. In Table IV below, the results for compound 1587 are presented, and for comparative compounds designated 1001 and 1093 and described in PCT / GB96 / 00580.

Table IV Compound 1001 disappeared immediately (less than one minute). Compound 1093 degraded after less than 13 hours. The majority of compound 1587 remained intact after 22 hours. Each of compounds 1001 and 1093 is a phosphoramidate of a nucleoside analogue. Compound 1001 is 5 ', 3'-dideoxy-2', 3'-didehydroadenosine 5 '- (phenylmethoxyalaninyl) phosphate. Compound 1093 is 5 '- (phenylmethoxyalaninyl) phosphoramidate 2', 3 '-dideoxy adenosine. The results shown in Table V above demonstrate the stability to acids of a compound which is an embodiment of the present invention, compared to known compounds.

BIOLOGICAL STABILITY Compound 1587 of the present invention and the two foregoing were tested for their stability towards biological decomposition. Each compound was incubated in normal heparinized human plasma at 37 ° C for 4 hours. At the selected times (0, 15, 30 minutes and 1, 2, 4 hours), samples were extracted in duplicate and treated by deproteinization by extraction in acetonitrile. The drug concentrations were subsequently determined by LC / MS / MS analysis using conventional procedures. The results are shown in Table V below.

Table V Under the conditions of the test, the data in Table V shows a stability of compound 1587 of more than 6 times with respect to compounds 1001 and 1093.

EXAMPLE 1 O-(Phenyl-ethoxy-L-alaninyl) phosphate succinate salt of (SS, 4R) -4- (2-amino-6-cyclopropylamino-9 (H) -purin-9-yl) -2-cyclopentene- 1-methanol (a) Phenylethoxy-L-alaninyl phosphorochloride L-alanine ethyl ester hydrochloride (3.0 g, 0.02 mol) in dry methylene chloride was suspended. (40 ml). To this suspension was added phenyl phosphorodichlorurate (2.9 ml, 0.02 mol) and the mixture was cooled to -80 ° C. N, N-diisopropylethylamine (Aldrich 6.8 ml, 0.04 mol) was added to the reaction in aliquots (1 to 2 ml) over a period of 1 hour. The reaction was allowed to warm slowly to room temperature while stirring for 2 hours. The organic solvent was removed in vacuo and the residue was treated with diethyl ether (100 ml). The diethyl ether solution was filtered to remove the insoluble inorganics and concentrated in vacuo to give the product as a colorless syrup. This product was used without further purification in part b. (b) O- (phenyl ethoxy-L-alaninyl) phosphate of (SS, 4R) -} i4- (2-amino-6-cyclopropylamino-9 (H) -purin-9-yl) -2-cyclopentene-1-methanol. It was dried (IS, 4R) -4- (2-amino-6-cyclopropylamino-9 (H) -purin-9-yl) -2-cyclopentene-1-methanol (1.5 g 52 mmol) by the addition of dioxane and concentration in vacuum. To the dried nucleoside was added anhydrous pyridine (10 ml) and tetrahydrofuran (20 ml). Then, tert-butyl magnesium chloride (6 ml, IM solution in tetrahydrofuran, 6 mmol) was slowly added. The reaction was stirred for 20 minutes and a solution of phenyl ethoxy-L-alaninyl phosphorochloride (part a, 3 g, 0.01 mol in 20 ml of tetrahydrofuran) was added. The reaction was stirred at room temperature for 10 hours and then concentrated in vacuo to a brown syrup.

This syrup was dissolved in methylene chloride (100 ml), the methylene chloride was extracted with water (2 x 100 ml), dried (MgSO4), filtered and concentrated to a solid brown foam. This solid foam was purified by flash chromatography using 5% methanol in chloroform as eluent, yielding 1.7 g (60%) of, after purification, a 4: 6 mixture of the phosphate isomers as a white solid foam. 1 H NMR (CDC13): d 7.47 (2 x s, 1 H), 7.10-7.46 (m, 5 H), 6.07 (, 1 H), 5.9 (, 1 H), 5.78 (s, 1 H), 5.5 (, 1 H), 4.84 (bs, 2H), 4.1 (m, 4H), 4.00 (m, 1H), 3.64 (m, 1H), 3.14 (m, 1H), 3.0 (, 1H), 2.78 (m, 1H), 1.68 ( m, 1H), 1.36 (2 xd, 3H), 1.22 (2 xt, 3H), 0.86 (, 2H), 0.6 (m, 2H); 31p NMR (CDC13): d 3.05, 3.02. Analysis calculated for C25H32N7? 5P x 1/4 C¡HC13: C, 53.07; H, 5.70; N, 17.15. Found: C, 52.81; H, 5.95; N, 16.91. (c) O- (phenyl-ethoxy-L-alanynyl) phosphthoate salt of (SS, 4R) -4- (2-amino-4-cyclopropylamino-9 (H) -purin-9-yl) -2- cyclopentene-1-methanol The O- (phenyl ethoxy-L-alaninyl) phosphate of (SS, 4R) -4- (2-amino-6-cyclopropylamino-9 (H) -purin-9-yl) was dissolved in ethanol. -2-cyclopentene-1-methanol (part lb, 376 mg, 0.7 mmol). To this solution was added succinic acid (82 mg, 0.7 mmol) and the resulting solution was evaporated to dryness. The residue was dissolved in acetonitrile (10 to 20 ml) with heating. A precipitate formed after cooling. The mixture was stored in the refrigerator overnight and a solid was collected by filtration to provide 330 mg (72%) of a 4: 6 mixture of the phosphate isomers as a solid. 1 H NMR (DMSO-dβ): d 12.14 (s, 2H), 7.58 (s, 1H), 7.1-7.4 (, 6H), 5.9-6.1 (m, 3H), 5.85 (s broad, 2H), 5.42 (, 1H), 3,954.1.5 (m, 4H), 3.8 (m, 1H), 3.05 (, 2H), 2.65 (m, 1H), 2.4 (s, 4H), 1.63 (m, 1H), 1.4 (2 xd, 3H), 1.12 (t, 3H), 0.5-0.7 (m, 4H); 31 P NMR (DMSO-d6): d 4.00 and 3.68; high resolution mass spectrum: Calculated for C25H32N7P5P (M + H) + (m / z) 542.2281. found 542.2282. Analysis calculated for C25H32N705P C4H604 1 / 2H20: C, 52.09; H, 5.87: N, 14.66. Found: C, 52.13; H, 5.72; N, 14.61.

EXAMPLE 2 O-Phenylmethoxy-L-alaninyl phosphate salt of (S, 4 R) -4- (2-amino-6-cyclopropylamino-9 (H) -purin-9-yl) -2-cyclopentene- 1-methanol (a) Phenylmethoxy-L-alaninyl phosphorochloride i The chloridrate of L-alanine methyl ester (10 g, 0.072 mol) in dry methylene chloride (100 ml) was suspended. To this suspension was added phenyl phosphorodichlorurate (10.7 g, 7.6 ml) and the mixture was cooled to -80 ° C. Next, N, N-diisopropylethylamine (Aldrich, 25 ml) was added to the reaction in aliquots (1 to 2 ml) over a period of 1 hour. The solution was stirred for 30 minutes at -80 ° C and then allowed to warm to room temperature slowly while stirring for 2 hours. The organic solvent was removed in vacuo and the residue was treated with diethyl ether (100 ml). The solution in diethyl ether was filtered to remove the insoluble inorganics. and concentrated in vacuo affording the product with a colorless syrup: NMR of 31 (CDC13) d 8.61; 8.37 ppm. This product was used without further purification in Example 2b. (b) O- (Phenylmethoxy-L-alaninyl) phosphate of (SS, 4R) l- (2-amino-6-cyclopropylamino-9 (H) -purin-9-yl) 2-cyclopentene-1-methanol dried (IS, 4R) -4- (2-amino-6-cyclopropylamino-9 (H) -purin-9-yl) -2-cyclopentene-1-methanol (5.5 g, 0.018 mol) by the addition of dioxane and Concentration to vacuum. To the dried nucleoside was added anhydrous tetrahydrofuran (30 ml) and pindine (40 ml). Then, tert-butyl magnesium chloride (23 ml, IM solution in tetrahydrofuran, 1.3 equivalents) was slowly added. The reaction was stirred for 20 minutes and a solution of phenylmethoxy-L-ala? -yl phosphorochloride was added. (12 g, 0.043 mol, 2.5 equivalents in 20 ml of THF). The reaction was stirred at room temperature for 12 hours and then concentrated in vacuo to a brown syrup. This syrup was dissolved in methylene chloride (100 ml), the methylene chloride was extracted with water (2 x 100 ml), dried (MgSO 4), filtered and concentrated to a brown foam. This foam was purified by flash chromatography using 5% methanol I in chloroform as eluent, yielding 6.9 g (75%) of a mixture of the phosphate isomers of the title compound as a white solid foam. XR NMR (CDC13): d 7.5 (2 x s, 1H), 7.1-7.4 (m, 5H), 6. 1 (m, 1H), 5.9 (m, 2H), 5.5-5.6 (m, 1H), 4.9 (bs, 2H), 4. 2 (m, 2H), 4.05 (m, 1H), 3.7 (s, 3H), 3.6-3.8 (m, 1H) 3.17 (m, 1H), 3.0 (m, 1H), 2.8 (m, 1H), 1.7 (m, 1H) r¡ 1.4 (2 x d, 3 H), 0.9 (m, 2 H), 0.6 (m, 2 H); 31P NMR (CDC13): d 3.07, 3.02. Analysis calculated for C24H30N7O5P x 2/5 CHC13: C, 50.94; H. 5.33, N, 17.00. Found: C, 50.83; H. 5.39, N, 16.94. (c) O- (Phenylmethoxy-L-alanynyl) phosphate salt of (SS, 4R) -4- (2-amino-6-cyclopropylamino-9 (H) -purin-9-yl) -2-cyclopentene -l-methanol The 0- (phenylmethoxy-L-alaninyl) phosphate of (SS, 4R) -4- (2-amino-6-cyclopropylamino-9 (H) -purin-9-yl) -2- was dissolved. Cyclopentene-1-methanol (part b, 100 mg, 0.19 mmol) in methanol. To this solution was added succinic acid (22 mg, 0.19 mmol) and the resulting solution was evaporated to dryness. The residue was dissolved in acetonitrile (10 ml) with heating. After cooling, a precipitate formed. The mixture was stored in the refrigerator overnight and a solid was collected by filtration, yielding 70 mg (57%) of a mixture of the phosphate isomers as a solid. XH NMR (DMS0-d6): d 12.15 (s, 2H, exchangeable D20), 7.61 (s, 1H), 7.36 (3H, becomes 2H when changing to D20), 7.20 (3H), 5.9-6.1 ( m, 3H), 5.88 (s broad, 2H, interchangeable D20), 5.44 (m, 1H), 4.0-4.2 (, 2H), 3.85 (m, 1H), 3.60 (s, 3H), 3.05 (2H), 2.65 (m, 1H), 2.44 (s, 4H), 1.64 (m, 1H), 1.23 (m, 3H), 0.5-0.7 (, 4H); 31P NMR (DMSO-d6): d; 3.99 and 3.66; Analysis calculated for C 24 H 3 o N 7? 5 P C 4 H 604 1/2 H 20: C, 51.38; H, 5.70; ?, 14.98. Found: C, 51.36; H, 5.66; ?, 14.99.

EXAMPLE 3 Salt of (1S, 4R) -4- (2-amino-6-cyclopropylamino-9 (H) -purin-9-yl) -2-cyclopentenoyl O- (phenyl ethoxy-L-alaninyl) phosphate 1-methanol 0- (phenyl ethoxy-L-alaninyl) phosphate of (1S, 4R) -4- (2-amino-6-cyclopropylamino-9 (H) -purin-9-yl) -2- was dissolved in ethanol. Cyclopentene-1-methanol (198 mg, 0.37 mmol). To this solution was added fumaric acid (43 mg, 0.37 mmol) and the resulting solution was evaporated to dryness. The residue was dissolved in acetonitrile (10 ml) with heating. After cooling, a precipitate formed. The mixture was stored in the refrigerator overnight. and the solid was collected by filtration to give 185 mg (75%) of a 4: 6 mixture of the phosphate isomers as a solid. NMR of XH (DMSO-d6): d 7.6 (s, 1), 7.1-7.4 (m, 6H), 6.64 (s, 2H), 5.9-6.1 (, 3H), 5.87 (s broad, 2H), 5.44 (m, 1H), 3.95-4.15 (m, 4H), 3.84 (m, 1H), 3.05 (m, 2H), 2.65 (, 1H), 1.63 (, 1H), 1.23 (, 3H), 1.15 (t , 3H), 0.5-0.7 (m, 4H); 31 P NMR (DMS0-d6): d; 4.00 and 3.67. Analysis calculated for C25H32N7O5P C4H404 1 / 2H20: C, 52.25; H, 5.59; N, 14.71. Found: C, 52.25; H, 5.51; N, 14.49.

EXAMPLE 4 O-(Phenyl-ethoxy-L-alaninyl) phosphate glutarate salt of (1S, 4R) -4- (2-amino-6-cyclopropylamino-9 (H) -purin-9-yl) -2-skypenten- 1-methanol It was dissolved in ethanol 0- (phenyl-ethoxy-L-alaninyl) phosphate of (SS, 4R) -4- (2-amino-6-cyclopropylamino-9 (H) -purin-9-yl) -2- cyclopentene-1-ethanol (part lb, 200 mg, 0.38 mmol). To this solution was added glutaric acid (50 mg, 0.38 mmol) and the resulting solution was evaporated to dryness. The residue was dissolved in acetonitrile (10 ml) with heating. The mixture was stored in the refrigerator overnight and the solid was collected by filtration, providing 130 mg (50%) of a 67:33 mixture of the phosphate isomers as a solid. NMR of 1 (DMS0-d6): d 7.6 (s, 1H), 7.1-7.4 (, 6H), 5.9-6.1 (, 3H), 5.87 (broad s, 2H), 5.44 (m, 1H), 3.95- 4.2 (m, 4H), 3.8 (m, 1H), 3.1 (m, 2H), 2.65 (m, 1H), 2.25 (t, 4H), 1.7 (m, 3H), 1.23 (m, 3H), 1.15 (t, 3H), 0.5-0.7 (m, 4H); 31p NMR (DMSO-d6): d; 4.00 and 3.68. Analysis calculated for C 25 H 32 N 7 5 5 P C 5 H 804 1/2 H 20: C, 52.78; H, 6.05; N, 14.36. Found: C, 52.97; H, 6.07; N, 14.33.

EXAMPLE 5 Salt D-Tartrate O (Phenyl-ethoxy-L-alaninyl) osphate of (1S, 4R) -4- (2-amino-6-cyclopropylamino-9 (H) -purin-9-yl) -2- cyclopentene-1-methanol 0- (phenyl ethoxy-L-alaninyl) phosphate of (SS, R) -4- (2-amino-6-cyclopropylamino-9 (H) -purin-9-yl) - was dissolved in ethanol 2-Cyclopentene-1-methanol (157 mg, 0.29 mmol). To this solution was added D-tartaric acid (44 mg, 0.29 mmol) and the resulting solution was evaporated to dryness. The residue was dissolved in acetonitrile (10 ml) with heating. The mixture was stored in the refrigerator overnight and the solid was collected by filtration to provide 112 mg of a 53:47 mixture of the phosphate isomers as a solid; NMR of "" "H (DMSO-d,): d 7.6 (s, 1H), 7.1-7.4 (m, 6H), 5.8-6.2 (, 5H), 5.44 (m, 1H), 4.3 (s, 2H) ), 3.95-4.2 (m, 4H), 3.8 (m, 1H), 3.35 (s I wide, 2H), 3.1 (m, 2H), 2.65 (m, 1H), 1.7 (, 1H), 1.23 (, 3H), 1.15 (t, 3H), 0.5-0.7 (m, 4H), 31P NMR (DMSO-d6): d, 4.00 and 3.67.

EXAMPLE 6 Diastereoisomers of (1- (4S) 4- (2-amino-6-cyclopropylamino-9 (H) -purin-9-yl) -2-cyclopentene O- (phenylmethoxy-L-alaninyl) osphate. -metanol ^^ M ^^ aMMte A approximately 1 |: 1 mixture of diastereomers of O- (phenylmethoxy-L-alaninyl) phosphate of (S, 4R) -4- (2-amino-6-cyclopropylamino-9 (H) was prepared. ) -purin-9-yl) -2-cyclopentene-l-methanol using a methodology similar to the previous one: 1H NMR (CDC13): d 7.5 (2 xs, 1H), 7.1-7.4 (m, 5H), 6.1 (m, 1H), 5.9 (, 2H), 5.5-5.6 (m, 1H), 4.9 (broad s, 2H), 4.2 (m, 2H), 4.05 (m, 1H), 3. 7 (s, 3H), 3.6-3.8 (, 1H) 3.17 (m, 1H), 3.0 (m, 1H), 2. 8 (m, 1H), 1.7 (m, 1H), 1.4 (2 x d, 3H), 0.9 (, 2H), 0.6 (m, 2H); 31P NMR (CDC13): d 3.07, 3.02. Analysis calculated for C 24 H 30 N 7 O 5 P x 2/5 CHCl 3 'C, 50.94; H, 5.33; N, 17.00 Found: C, 50.83; H, 5.39; N, 16.94. The phosphate isomers were separated with Supercritical Liquid Chromatography using a Chiralpak AS column, 25% methanol in carbon dioxide as eluent, a flow rate of 2 ml / min, temperature of 40 ° C and a pressure of 2.06 x 107 Pa. The first the isomer that eluted had a TR of 2.9 minutes and an enantiomeric purity of 100%; the evaporation of > the solvents provided the isomer as a white solid foam I: XH NMR (CDC13): d 7.50 (s, 1H), 7.3-7.4 (m, 2H), 7.15-7.25 (m, 3H), 6.11 (m, 1H), 5.91 (m, ¡1H), . 86 (s, 1H), 5.55 (, 1H), 4.89 (s, 2H), 4.24 (m, 2H), 4.05 (m, 1H), 3.72 (s, 3H), 3.65 (m, 1H), 3.20 ( m, 1H), 3.02 (, 1H), 2.83 (, 1H), 1.72 (m, 1H), 1.37 (d, 3H), 0.89 (m, 2H), 0.62 (m, 2H); 31 P NMR (CDC13): d 3.07. Analysis calculated for C2 H30N7? 5P x 1/7 CHC13: C, 53.25; H, 5.58; N, 18.00 Found C, 53.27, H, 5.69; N, 17.72. The second isomer that eluted had a TR of 6.7 minutes and an enantiomeric purity of 100%; evaporation of the solvents provided the isomer as a solid white foam: γE NMR (CDC13) • 'd 7.52 (s, 1H), 7.25-7.4 (, 2H), 7.15-7.22 (m, 3H), 6.11 ( m, 1H), 5.94 (m, 1H), 5.85 (s, 1H), 5.55 (m, 1H), 4.88 (s, 2H), 4.22 (m, 2H), 4.04 (, 1H), 3.75 (s, 3H), 3.7-3.75 (, 1H), 3.17 (m, 1H), 3.04 (m, 1H), 2.80 (m, 1H), 1.73 (m, 1H), 1.42 (d, 3H), 0.89 (m, 2H), 0.67 (m, 2H); NMR Analysis calculated for C24H30N7? 5P x 1/5 CHC13: C, 52.71; H, 5.52; N, 17.78. Found: C, 52.61; H, 567; N, 17.53.

EXAMPLE 7 Sodium salt of O- (phenyl N-methylamino-L-alaninyl) phosphate of (SS, 4R) -4- (2-amino-6-cyclopropylamino-9 (H) -purin-9-yl) -2- cyclopentene-l-methanol 0- (Phenylmethoxy-L-alanynyl) phosphate of (SS, 4R) -4- (2-amino-6-cyclopropylamino-9 (H) purin-9-yl) -2-cyclopentene was suspended -l-methanol (0.060 g, 0.11 mmol)! in a 40% aqueous methylamine solution (60 ml) and stirred at room temperature for 18 hours. The volatiles were removed by rotary evaporation in vacuo, and the residue was dissolved in water (50 ml), extracted with 1 dichloromethane (2 x 50 ml) and purified by anion exchange chromatography on a Sep-Pak® cartridge. Vac 35 cc Accell ™ Plus QMA (Waters Corp., P / N WAT 054725) (form HC0") with aqueous ammonium bicarbonate buffer (gradient from 0 to 0.5 M, 11) The appropriate fractions were combined and the volatiles were removed by vacuum rotary evaporation The residue was dissolved twice in deionized water and subjected to rotary evaporation in vacuo, yielding 0- '(phenyl N-methylamino-L-alaninyl) phosphate of (SS, 4R) -4- (2- amino-6-cyclopropylamino-9 (H) -purin-9-yl) -2-cyclopentene-1-methanol in the form of the ammonium salt This salt was dissolved in deionized water and passed through a Sep- Pak® Vac 20 cc Accell ™ Plus QMA (Ifiaters Corp., P / N WAT 054675) (Na + form) using deionized water. combined and lyophilized yielding 0.026 g (46% yield) of the sodium salt of O- (phenyl N-methylamino-L-alaninyl) phosphate of (SS, 4R) -4- (2-amino-6-cyclopropylamino-9 ( H) -purin-9-yl) -2-cyclopentene-1-methanol as the 2.2 hydrate as a white solid: MS (ES ") m / e 449 (MH"). Analysis calculated for Ci8H26N8Na? 4P 2.2 H20: C, 42.22; H, 5.98; N, 21.88. Found: C, 42.36; H, 5.77; N, 21.66.

EXAMPLE 8 Sodium salt of (1S, 4R) -442-amino-6-cyclopropylamino-9 (H) -purin-9-yl) -2-cyclopentene-O- (phenyl N-cyclopropylamino-L-alaninyl) phosphate -methanol The sodium salt of 0- (phenyl N-cyclopropylamino-L-alaninyl) phosphate of (SS, 4R) -4 (2-amino-6-cyclopropylamino-9 (H) -purin-9-yl) -2- Cyclopentene-1-methanol was prepared by a procedure similar to that used to prepare the sodium salt of (S, 4R) -4- (2-amino-6-phenyl-N-methylamino-L-alaninyl) phosphate. cyclopropylamino-9 (H) -purin-9-yl) -2-cyclopentene-1-methanol, except that the 40% methylamine aqueous solution was replaced by a solution of cyclopropylamine (5 mL, 72 mmol) in deionized water (50 mL). Freeze drying of the combined fractions provided mg (58% yield) of the sodium salt of O- (phenyl) N-cyclopropylamino-L-alaninyl) phosphate of (SS, 4R) -4- (2-amino-6-cyclopropylamino-9 (H) -purin-9-yl) -2- i cyclopentene-1-methanol as 2.5 hydrate in a white solid: MS (ES ") m / z 475 (MH"). Analysis calculated for C2oH28N8Na? 4P 2.5 H20: C, 44.20; H, 6.12; N, 20.61. Found: C, 44.27; H, 5.81; N, 20.49.

Example 9 Sodium salt of (1S, 4R) -4- (2-amino-6-cyclopropylamino-9 (H) -purin-9-yl) O- (phenyl N, N-dimethylamino-L-alaninyl) phosphate - 2-cyclopentene-1-methanol The sodium salt of O- (phenyl N, N-dimethylamino-L-alaninyl) phosphate of (SS, 4R) -4- (2-amino-6-cyclopropylamino-9 (H) -purin -9-yl) -2-cyclopentene-1-methanol was prepared by a procedure similar to that used to prepare the sodium salt of 0- (Phenyl-N-methylamino-L-alaninyl) phosphate of (SS, 4R) - ( 2-amino-6-cyclopropylamino-9 (H) -purin-9-yl) -2-cyclopentene-1-methanol, except that 40% methylamine aqueous solution was replaced by an aqueous solution of 40% dimethylamine ( 50 ml). Lyophilization of the combined fractions yielded 39 mg (59% yield) of the sodium salt of O- (phenyl, N, N-dimethylamino-L-alaninyl) phosphate of (SS, 4R) -4- (2-amino- 6-cyclopropylamino-9 (H) -purin-9-yl) -2-cyclopentene-1-methanol as the trihydrate as a white solid: MS (ES ") m / z 463 (MH"). Analysis calculated for Ci9H28 8Na? 4P 3.0 H20: C, 44.22; H, 6.34. N, 20.73. Found: C, 42. 0; H, 6.01; N, 20.51.

Example 10 Disodium salt of (1S, 4R) -4- (2-amino-6-cyclopropylamino-9 (H) -purin-9-yl) -2-cyclopenteno-1-methanol O- (L-alanynyl) phosphate O- (Phenylmethoxy-L-alaninyl) phosphate of (SS, 4R) -4- (2-amino-6-cyclopropylamino-9 (H) -purin-9-yl) -2-cyclopentene-l-methanol was suspended (0.5 g, 0.95 mmol) in a solution of triethylamine (30 ml) and deionized water (30 ml) and stirred at room temperature for 18 hours. The volatiles were removed by rotary evaporation in vacuo and the residue was dissolved in water (50 ml), extracted with dichloromethane (2 x 50 ml) and purified by anion exchange chromatography on a Sep-Pak® Vac 35 cc Accell cartridge. ™ Plus QMA (Waters Corp., P / N WAT 054725) (form HC0") with aqueous ammonia bicarbonate buffer (gradient from 0 to 0.5 M, 1 liter.) The appropriate fractions were combined and the volatiles were removed by rotary evaporation. The residue was dissolved twice in deionized water and subjected to rotary evaporation in vacuo to give 0- (L-alaninyl) phosphate of (S, 4 R) -4- (2-amino-6-cyclopropylamino). 9 (H) -purin-9-yl) -2-cyclopentene-1-methanol in the form of the ammonium salt This salt was dissolved in deionized water and passed through a Sep-Pak® Vac 20 cc Accell cartridge ™ Plus QMA (Waters Corp., P / N WAT 054675) (Na + form) using deionized water.The appropriate fractions were combined and lyophilized on providing 0.430 g (86% yield) of the disodium salt of O (L-alaninyl) phosphate of (SS, 4R) -4- (2-amino-6-cyclopropylamino-9 (H) -purin-9-yl) ) -2-cyclopentene-1-methanol as the 2.5 hydrate as a white solid: MS (ES ") m / e 436 (MH"). Analysis calculated for Ci7H22N7Na2? 5p 2.5 H20: C, 38.79; H, 5.17; N, 18.63. Found: C, 38.62; H, 5.11; N, 18.43.

Activity against Hepatitis B Virus The compounds of Examples 1 to 10 were tested for their activity against Hepatitis B virus 1 according to the procedure described by Jansen, R. et al., Antimicrobial Agents and Chemotherapy Vol. 37. No. 3. pages 441 to 447, '1993. The representative IC5o values were in the range of 0.017 μM to 3.0 μM.

Solubility and? stability in solution / solid state of the three salt forms of the O- (phenyl-ethoxy-L-alaninyl) phosphate of (1S, 4R) -4-12-amino-6- (cyclopropylamino) -9 (H) - purin-9-yl) -2-cyclopentene-l-methanol The salts have handling and formulation advantages because they are stable and fluid crystalline solids that do not change in composition, even at high temperatures and humidity. On the contrary, the free base of 0- (phenyl-ethoxy-L-alaninyl) -phosphate, (SS, 4R) -4- [2-amino-6 (cyclopropylamino) -9 (H) -purin-9-i]) -2- Cyclopentene-1-methanol is a hygroscopic amorphous solid foam that could not be crystallized.

Stability in solution =% of the promoter (AUC) after 27 hours at room temperature, normalized for the initial AUC. , i i Stability in solid state =% of the promoter (AUC) after 2 weeks at 60 ° C, normalized for the initial AUC.

The free bases of the phosphoramidates of '2', 3 'dideoxy adenosine and 2', 3 '-dideoxy-2', 3 '-didehydroadenosine are hygroscopic amorphous foams or gums. However, its instability to acids prevents the advantageous use of complexes with acids to form salts with improved physical properties; Exposure to acids degrades these compounds quickly. (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9 (H) -purin-9-yl] -2-cyclopentene-1-methanol (abacavir) has a higher acid solubility, compared with the nucleosides that contain labile glycosidic bonds between the heterocycle and the sugar. Thus, the protids phosphoramidate of abacavir form stable salts, which have been found to have advantageous physical properties suitable for pharmaceutical development.

It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is the conventional one for the manufacture of the objects or products to which it refers.

Claims

Having described the invention as above, the content of the following claims is claimed as property: 1. A compound of formula (1): characterized in that: Ar is an aryl group, R1 and R2 are independently selected from the group consisting of H, alkyl and aryl groups; X is selected from the group consisting of O, NH, NR 4 and S, R 4 being selected from the group consisting of alkyl and aryl groups; R5 is selected from the group consisting of H, alkyl and aryl groups, and when each of R1 and R5 is alkyl, they are attached to form a 5? Ring. or 6 links; and R3 is selected from the group consisting of H, alkyl, aryl, heterocyclic and polycyclic groups; or one of its pharmaceutically acceptable derivatives or metabolites. 2. A compound according to claim 1, characterized in that Ar is phenyl or substituted phenyl.
3. A compound according to any of claims 1 to 2, characterized in that R3 is selected from the group consisting of -CH3, -CH5 and -CH2Ph.
A compound of formula (II) characterized in that R1, R2, R3, R5 and X have the meanings described in claim 1. I
5. A compound according to any of claims 1 to 4, characterized in that R1 and R2 are the same or different and are H, -CH3 or -CH2CH2.
6. A compound according to any of claims 1 to 4, characterized in that R1 is H and R2 is -CH3 or -CH2-Ph.
7. A compound according to any of claims 1 to 6, characterized in that the C atom supporting R1 and R2 is chiral.
8. A compound according to any of claims 1 to 6, characterized in that the compound has chirality L with respect to the carbon atom supporting R1 and R.
9. A compound according to any of claims 1 to 8, characterized in that 'X is 0.
10. A compound selected from: I O- [Phenylmethoxy-L-alaninyl] phosphate of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. Diammonium salt of 0- [L-alaninyl] phosphate of (1S, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. 0- [Phenyl benzyloxy-L-alaninyl] phosphate (IS, 4R) 4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. 0- [Phenylmethoxy-D-alaninyl] phosphate of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. 0- [Phenylmethoxy-, -dimethylglycinyl] phosphate of (1S, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. 0- [Phenylmethoxy-L-phenylalaninyl] phosphate (1S, 4R) 4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. i O- [Phenyl-ethoxy-L-alaninyl] phosphate of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. 0- [Phenylmethoxiglicinyl] phosphate (1S, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. 0- [Phenyl L-aspartyl dimethyl ester] phosphate (IS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. 0- [4-chlorophenylmethoxy-L-alaninyl] phosphate of (1S, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. 0- [Phenyl-tert-butyloxy-L-alaninyl] phosphate of (1S, 4R) 4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. 0- [Phenyl n-propoxy-L-alaninyl] phosphate of (SS, 4R) -'4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol . O- [Phenyl n-butyloxy-L-alaninyl] phosphate of (lS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2- cyclopentene-1- methanol 0- [Phenyl] -propoxy-L-alaninyl] phosphate of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. 0- [(p (2-methyl, 2"-dimethoxypropionic) phenyl) methoxy-L-alaninyl] phosphate ester (SS, 4R) 4- [2-amino-6- (cyclopropylamino) -9H-purin- 9-yl] -2-cyclopentene-1-methanol. 0- [phenyl (2-methylpropyl) oxy-L-alaninyl] phosphate of i (IS, 4R) 4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1 -methanol. 0- [Phenyl (2,2-dimethylpropyl) oxy-L-alaninyl] phosphate of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene -l-methanol. 0- [Phenyl-3-methylbutyloxy-L-alaninyl] phosphate of (1S, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. O- [phenyl3-pentyloxy-L-alaninyl] phosphate of (lS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2- I cyclopentene-1-methanol . O- [Phenylmethoxy-L-valinyl] phosphate of (SS, 4R) -14- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. O- [Phenyl-3, 3-dimethyl-l-butyloxy-L-alaninyl] phosphate of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9- iJ] -2- cyclopentene-l-methanol .. O- [Phenyl-n-pentyloxy-L-alaninyl] phosphate of (1S, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. O- [Phenyl-cyclohexyloxy-L-alaninyl] phosphate of (1S, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. O- [Phenyl-cyclohexanomethoxy-L-alaninyl] phosphate of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. O- [Phenylmethoxy-3-cyclohexane-L-alaninyl] phosphate of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1- methanol 0- [4-Bromophenylmethoxy-L-alaninyl] phosphate of (1S, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. 0- [Phenyl-diethylo-L-aspartyl] phosphate of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. 0- [Phenylmethoxy-L-methionyl] phosphate of (SS, 4R) - < 4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. 0- [Phenylmethoxy-L-leucinyl] phosphate of (SS, 4R) -? 4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. 0- [Phenylmethoxy-L-prolinyl] phosphate of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. O- [Phenyl-dibenzyloxy-L-aspartinyl] phosphate of (1S, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. O- [Phenyl 4-methyl-l-pentyloxy-L-alaninyl] phosphate of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene- l-methanol. 0- [Phenyl-cyclopentylmethoxy-L-alaninyl] phosphate I of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. O- [4-fluorophenylmethoxy-L-alaninyl] phosphate of (1S, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. O- [4-Iodophenylmethoxy-L-alaninyl] phosphate of (1S, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. O- [Phenyl dimethoxy-L-glutamyl] phosphate of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. I O- [Phenylmethoxy-L-tryptophanyl] phosphate of (SS, 4R) 4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. O- [Phenylmethoxy-L-isoleucinyl] phosphate of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. O- [Phenyl-cycloheptanyloxy-L-alaninyl] phosphate of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. O- [Phenyl-cyclobutylmethoxy-L-alaninyl] phosphate of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. O- [Phenyl-cyclopropylmethoxy-L-alaninyl] phosphate of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. O- [Phenyl-cyclobutyloxy-L-alaninyl] phosphate of (1S, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. jjj ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ - ^^ _ ^, O- [Phenyl-cyclopentyloxy-L-alaninyl] phosphate of (1S, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. 5 0- [Phenyl-phenetoxy-L-alaninyl] phosphate of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. - 0- [Phenyl-3-phenyl-1-propoxy-L-alaninyl] phosphate (from 10 (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2- cyclopentene-l-methanol. 0- [Phenyl 4-phenyl-1-butoxy-L-alaninyl] phosphate of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -15 2-cyclopentene -l-methanol. 0- [Phenyl-2-cyclohexyl-l-ethoxy-L-alaninyl] phosphate of (SS, R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene- l-methanol. 0 0- [Phenyl-3-cyclohexyl-l-propoxy-L-alaninyl] phosphate of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene -l-methanol. 5 O- [Phenyl-4-cyclohexy-l-butoxy-L-alaninyl] phosphate of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2- cyclopentene-l-methanol. 0- [Phenylmethoxy-a-ethyl-L-glycine] phosphate of (lS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1- methanol 0- [Phenylmethoxy-a-phenyl (RS) glycinyl] phosphate of (1S, 4R) 4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol . O- [Phenylmethoxy-a-propyl-L-glycine] phosphate of (lSi, 4R) 4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol . O- [Phenylmethoxy-a-butyl-L-glycine] phosphate of (1SI, 4R) 4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol . O- [p-Phenoxyphenyl methoxy-L-alaninyl] phosphate of (1S, 4R) 4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. O- [p-phenylphenylmethoxy-L-alaninyl]] phosphate of (1S, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol . O- [4-hydroxyacetophenone methoxy-L-alaninyl] phosphide of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-l-methanol . O- [4-Butylphenylmethoxy-L-alaninyl] phosphate of (1S, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. O- [p-methoxyphenylmethoxy-L-alaninyl] phosphate of (1S, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. O- [p-Propoxyphenyl methoxy-L-alaninyl] phosphate of (1S, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. O- [Phenylmethoxy-a, α-cyclopentylglycinyl] phosphate of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-y1] -2-cyclopentene-1-methanol . O- [Phenylmethoxy-a, a-cyclohexylglycinyl] phosphate, of (SS, R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol . 0- [Phenylmethoxy-a, α-cyclopropylglycinyl] phosphate of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. O- [p (Methoxycarbonyl) phenylmethoxy-L-alaninyl] phosphate of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1- methanol 0- [p (trifluoromethylthio) phenylmethoxy-L-alaninyl] phosphate of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene- 1- methanol O- [p- (2-Methoxyvinyl) phenylmethoxy-L-alaninyl] phosphate of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene -l-methanol. 0- [p- (2-phenylcarbonylvinyl) phenylmethoxy-L-alaninyl] phosphate of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene -l-methanol. O- [p- (2, 2-dicyanovinyl) phenylmethoxy-L-alaninyl] phosphate of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2 -cyclopentene-1-methanol. 0- [o- (ethylcarboxylate ester) phenylmethoxy-L-alaninyl] phosphate of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene -l-methanol. Salt 0- (phenyl ethoxy-L-alaninyl) phosphate succinate of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-i, l] -2-cyclopentene-1 -methanol. Salt 0- (phenylmethoxy-L-alaninyl) phosphate succinate of (1S, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol . Salt fumarate 0- (phenyl ethoxy-L-alaninyl) phosphate of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-l-methanol . Glutarate salt of O- (phenyl ethoxy-L-alaninyl) phosphate of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cielope dye-1- methanol Salt D-tartrate 0- (phenyl ethoxy-L-alaninyl) fos f ato (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol. Diastereoisomers of 0- (phenylmethoxy-L-alaninyl) phosphate of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-skypentene-1- methanol Sodium salt of 0- (phenyl N-methylamino-L-alaninyl) -phosphate of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-pureJn-9-yl] -2-cyclopentene -1-methanol. Sodium salt of 0- (phenyl N-cyclopropylamino-L-alaninyl) phosphate of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-l -methanol. Sodium salt of O- (phenyl N, N-dimethylamino-L-alaninyl) phosphate of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene -l- I methanol. Disodium salt of O- (L-alaninyl) phosphate of (SS, 4R) -4- [2-amino-6- (cyclopropylamino) -9H-purin-9-yl] -2-cyclopentene-1-methanol.
11. A compound according to any of claims 1 to 10, characterized by being used in a method of treatment, prophylaxis or diagnosis.
12. Use of a compound according to any of claims 1 to 10, characterized by the preparation of a medicament for the treatment or prophylaxis of a viral infection.
13. Use of a compound according to claim 12, characterized in that the viral infection comprises HIV.
14. Use of a compound according to claim 12, characterized in that the viral infection comprises HBV.
15. A method of prophylaxis or treatment of a viral infection characterized in that it comprises administering to a patient in need of treatment, an effective dose of a compound according to any of claims 1 to 10.
16. A method according to claim 15, characterized in that the viral infection is HIV.
17. A compliance procedure cpn claim 15, characterized in that the viral infusion is HBV.
18. A method according to any of claims 15 to 17, characterized in that it comprises administering orally to a patient an effective dose of the compound.
19. A pharmaceutical composition characterized in that it comprises a compound according to any of claims 1 to 10 in combination with a pharmaceutically acceptable excipient.
20. A composition according to claim 19, characterized in that it is in a form for oral administration.
21. A process for preparing a compound according to any of claims 1 to 10, characterized in that it comprises reacting a compound having the formula with a compound of the formula MIMflHÉttUUHTI¿ÉÉÉ ~ 1. . ^ v- *