2-Deoxy Sugars. III. Nucleosides Derived from 2,6-Dideoxy-D-ribo-hexopyranose (Digitoxose) and 2-Deoxy-D-arabino-hexopyranose (2-Deoxyglucose)¹

Abstract

Previously, we reported the preparation of two crystalline 0-p-nitrobenzoyl halides of 2,6-dideoxy-D-ribo-hexopyranose (digito~ose).~ Subsequently, we were able to couple crystalline 3,4-di-O-pnitrobenzoyl-p-D-ribo-hexosyl chloride (I) with digitoxigenin to give, after removal of the protecting groups, a 2-deo~ycardenolide.~ This success prompted us to investigate the possibility of extending this direct method of synthesis of 2-deoxyglycosides to the preparation of some new 2'-deoxynucleosides as possible anticancer compounds.The extreme reactivity of the chloride I precluded any conditions involving elevated temperatures lest elimination of hydrogen chloride take place before coupling could be accomplished.Fortunately, I coupled readily with chloromercuri-6-benzamidopurine in dry dichloromethane at room temperature to give the protected nucleoside IV as semiamorphous material. Without further CH3 r purification, IV was deacylated giving crude 9-(2,6-dideoxy-~-ribo-hexopyranosyl)adenine (V), which was purified via its picrate salt and was isolated as a crystalline monohydrate. The yield of the nucleosjde V was 28% based on chloromercuri-6-benzamidopurine. Colorimetric estimation of the digotoxose content of the nucleoside V employing xanthydrol reagent gave results in excellent agreement with the calculat'ed value. A small quantity of V was hydrolyzed by means of dilute mineral acid and the resulting hydrolysis mixture was resolved by paper chromatography. This technique disclosed two components which were identified as adenine and digotoxose, respectively.Repeated attempts to couple I a t room temperature with mercury derivatives of thymine6 resulted

Nonequilibrium opioid antagonist activity of 6,14-dideoxynaltrexone derivatives

“…The target compounds (3)(4)(5)(6) are related to reported4,7 affinity labels that were found to possess irreversible opioid antagonist activity in smooth muscle preparations. The absence of the 14-OH group is the only structural difference between 3-6 and the reported series.…”

“…All target compounds (3)(4)(5)(6) were tested on the GPI for irreversible antagonism of the agonist effect of morphine or EK and on the MVD for irreversible blockage of morphine or DADLE (Table I). This testing involved the determination of the IC50 value of the standard agonist, washing (3 X 10 mL), and then redetermining the IC50 value in the same tissue after incubation (30 min) with the target compound followed by thorough washing (20 X 10 mL).…”

“…The agonist potencies for the target compounds (3)(4)(5)(6) are listed in Table II. On the GPI, all compounds except 4 were substantially more potent than morphine.…”

Preparation of 5-Benzyluracil and 5-Benzylcytosine Nucleosides as Potential Inhibitors of Uridine Phosphorylase

“…1-(2-deoxy-β-D-glucopyranosyl)thymine 1,8 which represents one of the most effective (1), prepared by addition of hydrogen bromide to tri-O-acetyl-D-glucal 9 . The nucleosidation reaction of the 1-bromohexose 1 with silylated 5-benzyluracil was performed in acetonitrile under catalysis with trimethylsilyl triflate.…”