Nucleic acid related compounds. 42. A general procedure for the efficient deoxygenation of secondary alcohols. Regiospecific and stereoselective conversion of ribonucleosides to 2'-deoxynucleosides

Robins, Morris J.; Wilson, John S.; Hansske, Fritz

doi:10.1021/ja00350a052

Cited by 479 publications

(207 citation statements)

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“…Our route (Scheme 1) starts with the synthesis of 2′-deoxy-2′-aminoadenosine (1) 20,26 and its quantitative conversion to 2′-deoxy-2′-aminoinosine (2) by preparative use of adenosine deaminase. 31 Trifluoroacetylation of the C2′ amine and acetylation of the C3′ and C5′ hydroxyls to yield 2′-deoxy-2′-trifluoroacetamidoinosine (3) and 2′-deoxy-2′-trifluoroacetamido-3′,5′-O-(diacetyl)-inosine (4), respectively, is accomplished in greater than 95% yield for each step.…”

Section: Chemistrymentioning

confidence: 99%

Adenosine Analogues as Selective Inhibitors of Glyceraldehyde-3-phosphate Dehydrogenase of Trypanosomatidae via Structure-Based Drug Design

et al. 2001

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In our continuation of the structure-based design of anti-trypanosomatid drugs, parasite-selective adenosine analogues were identified as low micromolar inhibitors of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Crystal structures of Trypanosoma brucei, Trypanosoma cruzi, Leishmania mexicana, and human GAPDH's provided details of how the adenosyl moiety of NAD + interacts with the proteins, and this facilitated the understanding of the relative affinities of a series of adenosine analogues for the various GAPDH's. From exploration of modifications of the naphthalenemethyl and benzamide substituents of a lead compound, N 6 -(1-naphthalenemethyl)-2′-deoxy-2′-(3-methoxybenzamido)adenosine (6e), N 6 -(substituted-naphthalenemethyl)-2′-deoxy-2′-(substituted-benzamido)adenosine analogues were investigated. N 6 -(1-Naphthalenemethyl)-2′-deoxy-2′-(3,5-dimethoxybenzamido)adenosine (6m), N 6 -[1-(3-hydroxy-naphthalene)methyl]-2′-deoxy-2′-(3,5-dimethoxybenzamido)adenosine (7m), N 6 -[1-(3-methoxy-naphthalene)methyl]-2′-deoxy-2′-(3,5-dimethoxybenzamido)adenosine (9m), N 6 -(2-naphthalene-methyl)-2′-deoxy-2′-(3-methoxybenzamido)adenosine (11e), and N 6 -(2-naphthalenemethyl)-2′-deoxy-2′-(3,5-dimethoxybenzamido)adenosine (11m) demonstrated a 2-to 3-fold improvement over 6e and a 7100-to 25000-fold improvement over the adenosine template. IC 50 's of these compounds were in the range 2-12 μM for T. brucei, T. cruzi, and L. mexicana GAPDH's, and these compounds did not inhibit mammalian GAPDH when tested at their solubility limit. To explore more thoroughly the structure-activity relationships of this class of compounds, a library of 240 N 6 -(substituted)-2′-deoxy-2′-(amido)adenosine analogues was generated using parallel solution-phase synthesis with N 6 and C2′ substituents chosen on the basis of computational docking scores. This resulted in the identification of 40 additional compounds that inhibit parasite GAPDH's in the low micromolar range. We also explored adenosine analogues containing 5′-amido substituents and found that 2′,5′-

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Section: Chemistrymentioning

confidence: 99%

Adenosine Analogues as Selective Inhibitors of Glyceraldehyde-3-phosphate Dehydrogenase of Trypanosomatidae via Structure-Based Drug Design

et al. 2001

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“…In order to deoxygenate the tricyclic keto ketal (12) according to procedure reported by Robins and coworkers [23,24], the corresponding alcohol (18) or (19) is needed as a precursor. Results from earlier work by Story indicated that the stereochemistry of alcohols may have an effect on the yield and ease of preparation of phenyl thionocarbonate derivatives, and subsequently on the yield of deoxygenated product [25].…”

Section: Deoxygenation Of the Tricyclic Ketone (12)mentioning

confidence: 99%

“…Results of the reductions are summarized in the Table 2. The phenyl thionocarbonates (20) and (21), required by Robins' procedure, were prepared in 76% and 71% yield, respectively, from the reaction between the corresponding alcohols (18) and (19) and phenyl chlorothionoformate, in the presence of DMAP [23,24]. The phenyl thionocarbonates (20) and (21) were reduced to the triquinane (13) in refluxing benzene with tributyltin hydride and a small amount of AIBN, as a radical initiator.…”

Section: Deoxygenation Of the Tricyclic Ketone (12)mentioning

confidence: 99%

Synthesis of a Highly Functionalized Triquinane: Studies Towards a Total Synthesis of Subergorgic Acid and Its Analogues

Dragojlović

2000

Molecules

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“…General approach for the removal of 2 -OH of arylamine-modified guanosines. modified Barton deoxygenation method (27,28) to remove the 2'-hydroxyl groups (Scheme 1). The protection of the 3' and 5' hydroxyl groups as the tetraisopropyl disiloxane derivatives (Structure 20) was accomplished by using 1,1',3,3'-tetraisopropyl-dichlorodisiloxane.…”

Section: Further Oxidation and Structure Studiesmentioning

confidence: 99%

Synthetic and oxidative studies on 8-(arylamino)-2'-deoxyguanosine and -guanosine derivatives.

Johnson

Huang²,

Yu³

1994

Environ Health Perspect

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Facile aerial oxidation is a general feature of guanine ribo-and 2'-deoxyribonucleosides that are substituted at the 8-position by an aminoaryl group. In previous work, it had been suggested that two of the major oxidation products are a pair of diastereomers having a spiro structure. These were presumed to be related by a chiral difference at the spiro carbon atom. The pattern of the oxidative process involves a contraction of the pyrimidine ring. It was thought to be analogous to that suggested by other investigators for the oxidation of uric acid, but for which no really definitive evidence had been presented. We have been able now to isolate in a crystalline state one of the diastereomers produced by the aerial oxidation of 8-phenylaminoguanosine under alkaline conditions. Analysis by X-ray diffraction has now confirmed the type of spiro structure promulgated previously. These findings also imply that spiro compounds are likely to be produced during the aerial oxidation of any 8-arylaminoguanine nucleoside or 2'-deoxynucleoside. In addition, this work adds considerable weight to the results of Poje and Sokolic-Maravic who proposed that a spiro intermediate is produced during the aerial oxidation of uric acid (12,13). However, they found this compound to be unstable to base, in contrast to the arylaminoguanine oxidation products. In the course of the above work we showed that the 8-arylamino derivatives of guanosine can be converted by the Barton deoxygenation method to the corresponding 2'-deoxyribonucleosides. This makes available a number of the latter compounds, which are not easily prepared by other methods.

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Nucleic acid related compounds. 42. A general procedure for the efficient deoxygenation of secondary alcohols. Regiospecific and stereoselective conversion of ribonucleosides to 2'-deoxynucleosides

Cited by 479 publications

References 1 publication

Adenosine Analogues as Selective Inhibitors of Glyceraldehyde-3-phosphate Dehydrogenase of Trypanosomatidae via Structure-Based Drug Design

Adenosine Analogues as Selective Inhibitors of Glyceraldehyde-3-phosphate Dehydrogenase of Trypanosomatidae via Structure-Based Drug Design

Synthesis of a Highly Functionalized Triquinane: Studies Towards a Total Synthesis of Subergorgic Acid and Its Analogues

Synthetic and oxidative studies on 8-(arylamino)-2'-deoxyguanosine and -guanosine derivatives.

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