5 -fluorosulfonylbenzoyl 5 -adenosine

S -p-Fluorosvlfonylbemoyladenosine. The 5 -p-fluorosulfonylbenzoyl-adenosine is most readily prepared by reaction of adenosine with p-fluoro-sulfonylbenzoyl chloride by a modification of the procedure of Pal, Wechter, and Colman Adenosine (1.13 g, 4.2 mmoles) is dissolved in 10 ml of hexamethyl phosphoric triamide by warming to 50° in a water bath. Upon cooling, p-fluorosulfonylbenzoyl chloride (1.32 g, 6 mmoles) is added, and the mixture is allowed to stand at room temperature for 18 hr. The reaction mixture is extracted once with 30 ml of petroleum ether. After separation of the two layers, the product is precipitated from the lower layer by the slow addition of 40 ml of ethyl acetate diethyl ether (1 1). The product is collected by filtration and air dried. This procedure yields between 1.6 (2.5 mmoles) and 2.0 g (3.1 mmoles) of... 

The purity of the 5 -p-fluorosulfonylbenzoyl adenosine can be assessed by thin-layer or descending paper chromatography. With EM silica gel F-254 (fast running) thin-layer plates on aluminum and a solvent system composed of methyl ethyl ketone acetone water (60 20 15), the Rf for 5 FSBA is 0.76, whereas that for 3 -FSBA is 0.80. With a solvent consisting of methanol chloroform (15 85) the Rf for 5 -FSBA is 0.56, whereas that for 3 -FSBA is 0.64. In descending paper chromatography (Whatman No. 3 MM), with n-butanol acetic acid water (4 1 5) as solvent, the 5 -FSBA exhibits an Rf of 0.76, whereas the 3 -FSBA has an Rf of 0.86. 

S -p-Fluorosulfonylbenzoyladenosine. The 3 -FSBA is prepared by reaction of adenosine with p-fluorosulfonylbenzoyl chloride in the presence of the base, 1,5 diazabicyclo [3.4.0] nonene-5, to accept the mole of HCl from the reaction of the acid chloride with the alcohol, in a modification of the procedure of Pal, Wechter, and Colman. The initial crude product is a mixture in which 3 -FSBA predominates substantial amounts of 5 -FSBA as well as smaller amounts of 2, 3 -bis-p-fluorosulfonylbenzoyl-adenosine and 2, 3, 5 -Tris-p-fluorosulfonylbenzoyladenosine are also detected. The 3 -FSBA is purified from the mbcture. A typical preparation is as follows Adenosine (0.80 g, 3 mmoles) is dissolved in 15 ml of dimethylformamide and 1,5-diazabicyclo [3.4.0] nonene-5 (0.37 g, 3 mmoles) is added. After the mixture has been stirred for 2 hr at room temperature. 

Fig. 3. Reaction of 5 -p-fluorosulfonylbenzoyl adenosine with bovine liver glutamate dehydrogenase. Glutamate dehydrogenase (051 mg/ml) was incubated with 5 -FSBA (0.43 mM) at 30° in 0.01 M sodium barbital buffer, pH 8, containing 0.4 M KCl and 5% ethanol. At the indicated times, aliquots were withdrawn, diluted 20-fold with Tris-0.1 M acetate buffer pH 8 at 0°, and assayed (A) in the absence and (B) in the presence of 1(X) nM ADP using 100 nM TPNH as coenzyme.

Difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-pentanoic acid 4,ll-bis[(2-Aminoethyl)amino]anthra[2,3-b]furan-5,10-diones 4(l-Anilino-podophyllotoxin derivatives 5-Aza-2 -deoxycytidine 5-Bromotetrandrine 5-Cyclohexylindolyl-2 -deoxyribose (non-natural nucleoside) 5 -Fluorosulfonylbenzoyl 5 -adenosine 5-Fluorouracil 5,5-Diphenylbarbituric acid 6-[(2S,4R,6E)-4-Methyl-2-(methylamino)-3-oxo-6-octenoic acid] cyclosporine D (PSC833) 6-Hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid 6-Mercaptopurine 6-Prenylchrysin 6-Thioguanine 6,7-Dimethoxy-... 

The accumulation of data indicates the 3 isomers to be the specific components isolated under our synthetic conditions. Further support for this conclusion is seen in the recent observation that the esterification of adenosine with fluorosulfonylbenzoyl chloride results in the preferential formation of 3 -p-fluorosulfonylbenzoyladenosine. ... 

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