Adenosine 2’-deoxy-, preparation

Cladribine. Cladrihine, Leustatin. 2-CdA, NSC-1050 14-F. 2-chlorodeoxyadcnosine. 2-chloro-2 -deoxy- o-adenosine. is prepared by a multistep procedure from 2.8-dichloroudcnine and o-xylo.sc, and i.s supplied as a I mg/ mL sterile solution in 0.9% Sodium Chloride for Injection, USP. The desired dose is removed from the vial and diluted with normal. saline for infusion over 24 hours. Thc.se solutions arc stable for 72 hours. Infusion is continued for 5 to 7 days. 

Selective chlorination or bromination of the 5 -hydroxyl group in unprotected D-ribonucleosides has been achieved75 by treatment with thionyl chloride or thionyl bromide, respectively, in hexamethyl-phosphoric triamide at room temperature for 10-15 hours the 5 -deoxy-5 -halogeno derivatives of cytidine and adenosine have been prepared in this way. The reactions presumably occur by way of alkoxyphosphonium salts as intermediates.78... 

A mixture of 2-chloro-2 -deoxy-(3, 5 -0-tetraisopropyldisiloxyl)adenosine (2.5 g, 4.74 mM), and tetra-n-butylammonium fluoride (1.1 M, 8.6 mL, 9.46 mM) in tetrahydrofuran (10 mL) is stirred at room temperature under nitrogen for 2 hours. The solvent volume is reduced in vacuo and the resulting residue is treated with water (200 mL) and extracted with ether (3x20 mL). The aqueous layer is purified by preparative HPLC (C-18 reverse phase column, methanol/water 15 85 to 20 80) to yield the title compound (600 mg, 44%) MP >230°C. 

Deoxy-5 -guanidine adenosines derivatives, (I), were previously prepared by the author (2) and others (3). In an earlier investigation 2-fluoro-9-(2-deoxy-2-fluoro-/3-D-arabinofuranosyl)-9H-purin-6-amine, (II), and derivatives were also prepared by the author and are discussed (4). 

Chemical Synthesis.—Purine nucleoside 5 -monophosphates enriched with or 0 on the phosphate group are conveniently prepared by treating phosphorus pentachloride in dry triethyl phosphate with one equivalent of the appropriately labelled water to give PO]- or P 0]P0Cl3, which is not isolated but mixed with adenosine or guanosine in the same solvent. Work-up of the resulting 5 -phos-phorodichloridate in similarly labelled water permits the formation of pO]-or P 0]AMP (or GMP) in fair yield with good enrichment. The 5 -monophos-phates of the 5 -C-methyl uridines derived from 6-deoxy-D-allose and 6-deoxy-L-talose have been prepared via phosphorylation of the 2, 3 -0,0-ethoxymethyl-idene derivative of the nucleosides (1) with -cyanoethyl phosphate and DCC or TPS-Cl. The same method has been used to phosphorylate iV -benzoylated 2, 3 -0,C -isopropylidene derivatives of various 5 -C-alkyladenosine species (2) and also 4 -allyladenosine (3) as part of a study in which derivatives of AMP... 

Thus, 3 -amino-3 -deoxy-2, 3 -ieco-adenosine and 3 -deoxy-2, 3 -5eco-inosine were prepared, and the former was used for the synthesis of a seco-puromycin analogue, which was not capable of inhibiting protein synthesis in reticulocyte systems using globin mRNA (88T6419). 

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