8-chloro-2 -deoxyadenosine

Scheme 4. Coupled enzyme assays shifting the fluorinase reaction in favour of 5 -chloro-5 -deoxyadenosine (5 -CIDA) 14 synthesis [15].

Fig. 5. The X-ray-derived structure of the 5 -chloro-5 -deoxyadenosine (5 -CIDA)-fluorinase co-complex overlayed with the 5 -FDA structure. It can be seen that the chlorine atom is displaced relative to the location of the fluorine due to its larger size [15]. (See Colour Plate Section at the end of this book.)...

Beginning with the enantiomer of 27, the reaction sequence outlined in Fig. 4 was repeated, leading to compound 14 (63). Selective oxidation of 14 afforded the carboxylic acid 23(63). The arsenic-containing nucleoside 25 was obtained by treating 5 -chloro-5 -deoxyadenosine with excess dimethylarsinosodium and oxidation of the resultant arsine (63). 

The enzyme 5 -fluoro-5 -deoxyadenosine synthetase (5 -FDAS), utilizing SAM, catalyzes the formation of carbon-fluoride bonds. In fact, in presence of F , an 8 2 substitution of methionine at SAM generates the intermediate 5 -fluoro-5 -deoxyadenosine, which is subsequently converted to fluoroacetate and 4-fluorothreonine, whereas in the biosynthesis of salinosporamide A the enzyme achieves the chlorination step through the conversion to 5 -chloro-5 -deoxyadenosine (Section 4.2.2) (Figure 1.61) [51],... 

Chloro-A -demethyl-7-deoxy-3 -depropyl-3 -pentyllincomycin, M-315 2-Chloro-2 -deoxyadenosine, C-66 2 -Chloro-2 -deoxyadenosine, C-68 5 -Chloro-5 -deoxyadenosine, C-69... 

Bromo-5-deoxysorbose a-L-Pyranose-/orm 1,2-0-Isopropylidene, 3-Me, 4-(dimetbylcarbamyl), B-94 5-Bromo-5-deoxysorbose a-L-Pyranose- orm, B-94 5 -Bromo-5 -deoxytbymidine 3 -Ac, B-lOO 5 -Bromo-5 -deoxytbymidine, B-lOO 5-Bromo-2,5-dideoxy-D-i/irc -pentono-l,4-lactone, B-112 5-Bromo-2,5-dideoxy-D-cryi/ira-pentono-l,4-lactone, B-112 5 -Chloro-5 -deoxyadenosine, C-69 5 -Chloro-5 -deoxyarabinosylcytosine, C-77 5-Chloro-5-deoxyidofnraniirono-6,3-lactone p-L-ybrm ... 

The 3,3 -cycloadenosine derivative (605) and 5 -chloro-5 -deoxyadenosine 2, 3 -sulphate (606) were formed when adenosine reacted with sulphuryl chloride in acetonitrile. Solvolysis of (606) in aqueous ethanol resulted in opening of the pyrimidine ring and formation of the cyclonucleoside (607). 3,5 -Cycloadenosine was synthesized from 5 -chloro-5 -deoxyadenosine, which was prepared by treating adenosine with thionyl chloride in HMPT. 

S ATP -I- 2-chloro-2 -deoxyadenosine <3, 5> (<3> recombinant mitochondrial deoxyguanosine kinase [7] <5> recombinant mitochondrial deoxyguanosine kinase, 200% of activity with deoxyguanosine at 0.005 mM... 

Additional information <1> (<1>, the deletion mutants rDm-dNKAClO and rDm-dNKAC20 show the same substrate activity pattern as the recombinant wild-type enzyme. Relative phosphorylation of 2 -deoxycytidine and 2-chloro-2 -deoxyadenosine increases with increasing C-terminal truncation. The relative activities of rDm-dNKAClO and rDm-dNKAC20 with deoxyribonucleosides remains largely unchanged, whereas there is a substantial decrease in the phosphorylation of the purine ribonucleosides adenosine and guanosine, as well as of all dideoxyribonucleosides and 3 -azido-2 ,3 -dide-oxythymidine. The relative activities with the pyrimidine ribonucleosides and l-/l-D-arabinofuranosylcytosine and l-/i-D-arabinofuranosylthymine are not affected by the C-terminal deletions [4]) [4]... 

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. ... 

A typical example is the synthesis of 2-chloro-2 -deoxyadenosine (13) by fusion of 2,6-dichloropurine with 2-deoxy-l-0-methyl-3,5-di-C -(4-toluoyl)- -D-ribofuranose. ... 

Treatment of 6-chloro-9-(2-deoxy-3,5-di-0-(4-toluoyl)-/(-D-ribofuranosyl)purine with methanolic ammonia results in the deprotection of the glyconic moiety with concomitant nucleophilic displacement of the 6-chloro substituent to give 2 -deoxyadenosine (7), ... 

The photochemical method can also be applied to 2-chloro- and 2-bromo-2 -deoxyadenosines to give 2 -deoxyisoguanosine 8. ... 

The allyl group is introduced at the G -position of 2 -deoxyisoguanosine to give 10 by reaction of 2-chloro-2 -deoxyadenosine with sodium prop-2-enolate. ... 

Chloro-2 -deoxyadenosine (748 mg, 2.6 mmol) was added to a solution of sodium (0.8 g) dissolved in allyl alcohol (17mL). The solution was heated at 60°C for 2h and evaporated to dryness. The residue was co-evaporated with MeOH (10 mL) and placed on the top of a silica-gel-60 column. The elution was performed with CH Clj/MeOH (95 5) and CH CL/MeOH (70 30). The nucleoside containing fractions were evaporated to dryness yield 628 mg (79%). 

The protected hydrogen phosphonate of a 2 -deoxyadenosine tetracyclic analogue, (46) has been S5mthesised via the Stille biaryl coupling reaction of N-(rer/-butoxycarbonyl)-2-(trimethylstannyl)-aniline on a protected 6-chloro-7-deaza-7-iodopurine-2 -deoxyribose, followed by cyclisation. After subsequent deprotection and 5 -0-protection, the nucleoside analogue was treated with 2-chloro-4/7-l,3,2-benzodioxaphosphorin-4-one in the presence of pyridine. ... 

A variety of 4 -substituted tpys have been prepared, either by condensation to form the central ring or by Stille coupling of the pyridine components. The former approach, starting with ethyl 2-pyridinecarboxylate and acetone, leads to (25a) in three steps with an overall yield of 40%.25 This chloro-derivative can, in turn, be converted to a variety of other 4 -substituted tpys, such as (26a-g).26 The nucleosides 2 -deoxyadenosine and 2"-o-methyladenosine were similarly coupled with (25a) to afford the tpys (27), whose Cu11 complexes effected efficient site-specific cleavage of RNA.27... 

The majority of newly reported nucleoside 5 -monophosphates have been prepared using phosphorus oxychloride in trialkyl phosphate solution. These include the monophosphates of 2-fluoroadenosine, 2-amino-6-chloro-9-(/S-D-ribofuranosyl)-purine, bredinin (6), cordycepin 2 -azido-2 -deoxyadenosine, 2 -fluoro-... 

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