Deoxyadenosine, rearrangement

The analogons deamination reaction is not observed in l-methyl-2 -deoxy-adenosine nncleosides. ° Rather, in the adenine series, the Dimroth rearrangement occnrs (Scheme 8.4). On the contrary, in styrene adducts of 2 -deoxyadenosine, the hydroxyl residue of the adduct undergoes intramolecular reaction with the base to initiate deamination (Scheme 8.6). ° ° Similarly, cytosine residues bearing styrene adducts at the N3-position undergo rapid deamination (nearly complete deamination is seen within 75h). °°... 

Advances in the Dimroth rearrangement in the adenine series have been reviewed. A-l-Methoxy derivatives of adenosine and 2 -deoxyadenosine have been found to... 

At present most evidence favors, for the isomerization reactions, an enzyme-catalyzed rearrangement of the substrate radical produced initially during formation of the 5 -deoxyadenosine (Eq. 16-38).40CM01c... 

Little effort has been devoted to ascertain how the coenzyme is re-formed (the termination step). In the radical initiation step (ii, Figure 3), deoxyadenosine is formed. To re-form the Co-C bond to the 5 position of the nucleoside, a methyl group in the 5 -deoxy adenosine must be activated. Such activation requires either H atom abstraction, perhaps by the amino acid side chain radical or by a rearranged radical intermediate derived from the substrate (iv, Figure 3). This step is still not well understood. In the first edition of this volume [75], I expressed the hope that the steps that regenerate the coenzyme would become obvious once the rearrangement process was understood. Recent studies [67] to be described... 

A sugar derivative related to the purine nucleosides, namely methyl 5-(adenin-l-yl)-5-deoxy-2,3-0-isopropylidene-j8-D-ribofurano-side, is formed by the reaction of methyl 5-amino-5-deoxy-2,3-0-iso-propylidene-jS-D-ribofuranoside with l-benzyl-5-cyano-4[(ethoxy-methylene)amino]imidazole, followed by removal of the benzyl group. On fusion, this compound rearranges to methyl 5-deoxy-2,3-0-isopropylidene-5-[(purin-6-yl)amino]-/8-D-ribofuranoside, which can also be obtained from the reaction of methyl 5-amino-5-deoxy-2,3-0-isopropylidene-/8-D-ribofuranoside with 6-chloro-9-(tetrahydropyran-2-yl)purine. In the same manner, methyl 5-amino-5-deoxy-2,3-di-0-p-tolylsulfonyl-/3-D-ribofuranoside reacts with 6-chloro-9-(tetrahydro-pyran-2-yl)purine to give methyl 5-deoxy-5-[9-(tetrahydropyran-2-yl)-purin-6-yl]amino-2,3-di-0-p-tolylsulfonyl-j8-D-ribofuranoside. With liquid ammonia, 5 -0-p-tolylsulfonyladenosine gives 5 -amino-5 -deoxyadenosine. On heating in p-dioxane, ring closure to 3,5 -an-hydroadenosine is observed. ... 

N]-Labeled 3, 5 -bis-si ylated 2 -deoxyadenosine was alkylated at NI with benzyl bromide. Dimroth rearrangement, followed by oxidative removal of the benzyl group and desilylation (aq NH3), gave [l- N]2 -deoxyadenosine. ... 

In the laboratory of R.A. Jones, A/ -methoxy derivatives of adenosine and 2 -deoxyadenosine were found to undergo a facile Dimroth rearrangement The high-yielding process allowed the efficient synthesis of [1,7- N2]- and [1,7, NH2- N3] adenosine and 2 -deoxyadenosine that are important tools in the NMR studies of nucleic acid structure and interactions. The rearrangement was carried out in weakly acidic refluxing methanol. 

The mechanism in Figure 8 accounts for available information. At the active site of DDH, adenosylcobalamin exists with a small equilibrium amount of the 5 -deoxyadenosyl radical in complex 1. Abstraction of a hydrogen atom from Cl of the substrate by the nucleoside radical leads to 5 -deoxyadenosine and the substrate-related radical in complex 2. Radical rearrangement to the product-related radical in complex 3 is followed by abstraction of a hydrogen atom from the methyl group to regenerate the Co—C bond and form propionaldehyde hydrate in complex 4. Dehydration is followed by dissociation of propionaldehyde. 

Like glutamate, 2-methyleneglutarate can be fermented in Clostridia, albeit by a different pathway,and the reaction of MGM is the first step. Less information about MGM is available than other coenzyme Bi2-dependent enzymes. The stereochemistry, purification, and molecular characterization are available. A substrate-based free radical has been observed by EPR spectroscopy. The reaction mechanism is not known, although it likely follows the generic pathway of hydrogen abstraction by the 5 -deoxyadenosyl radical to form a substrate-derived radical, which rearranges to a product-related radical that is quenched by hydrogen transfer from 5 -deoxyadenosine. The mechanism of radical isomerization remains to be proven. ... 

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