Adenosine 5-trityl

It should be noted, however, that a stereospecific glycosylation of the sodium salt of adenine by 1,2-anhydro-5-0-trityl-L-ribofuranose to give 5 -0-L-adenosine in 90% yield had been previously published in 1969, ° but in this case a substituent at C2 of the sugar directs the stereochemistry of the incoming nucleophile. 

In 1933, Bredereck discovered that adenosine reacts with trityl chloride to give a raonotrityl-adenosine which, without direct experimental evidence, he assumed to be 5-trityl-adenosine. In support of this formulation he presented the observation that no reaction between trityl chloride and a mixture of a- and 8-methyl ribopyranosides (having no primary hydroxyl group) could be detected polarimetrically. 

On repeating the preparation of monotrityl adenosine, Levene and Tipson discovered that a quantity of a dt-trityl adenosine is invariably formed at the same time. They were able to separate the two products and showed their structures in the following manner. 

The tosyloxy groups of tritosyl adenosine were not replaced by iodine on treatment with sodium iodide, showing the absence of a tosyl group at position (5). Hence monotrityl-adenosine is 5-trityl-adenosine, and adenosine must have a furanose structure. 

The ditrityl-adenosine was acetylated to give diacetyl-ditrityl-adeno-sine which, on hydrolysis by means of boiling 80% acetic acid, yielded the same diacetyl-adenosine (having o free amino group) as was obtained by hydrolysis of iV -acetyl-2,3-diacetyl-5-trityl-adenosine under the same conditions. It follows that the diacetate is 2,3-diacetyl-adenosine and that ditrityl-adenosine is 9 -(5-trityl-ribofuranosyl)-6 -N-trityl-adenine. 

Improved syntheses have been described for cordycepin (3 -deoxy-adenosine), using 2, 3 -anhydro-adenosine in a high-yield, one-step procedure, the 3 -deoxy compound was obtained directly using lithium triethylborohydride alternatively, an N, 0 -bis-monomethoxy-trityl derivative was used with LAH, with subsequent deprotection. Both groups also prepared the 3-deuterio analogue (17). 

These difficulties were overcome in various ways, two of which were (1) isopropylidene tosyladenosine is condensed with vitamin B12 the acetone is removed from this compound by mild acid hydrolysis, and (2) the 5 -trityl adenosine is first synthesized and then converted to the 2, 3 -diacetyl trityl derivative, which is detritylated by dilute acid. The 2, 3 -diacetyl coenzyme is then prepared by tosylation and condensation. The compound is then deacetylated to give coenzyme Bi2 in good yields. 

An interesting new procedure was employed in the synthesis of L-adenosine, L-guanosine, L-cytidine, L-uridine, L-5-methyluridine, and L-6-azauridine, involving the reaction of 2-0-tosyl-5-0-trityl-L-arabinose (I) with a suspension of the sodium salt of the appropriate base in DMF, to give 32-92% yields of the 5 trityl derivatives of the corresponding L-p-ribofuranosides (111). The reaction presumably proceeds through an epoxide intermediate (II) resulting from the action of the base on 1. ... 

The 2 -hydroxy group of adenosine can be selectively blocked as a 4-methoxybenzyl ether, a new protecting group, by treatment with 4-methoxybenzyl bromide and sodium hydride. A mixture of the 2 -and 3 -ethers results if p-methoxyphenyl diazomethane is used in presence of stannous chloride. The ether protecting group was rapidly cleaved with trityl tetraf luoroborate. ... 

Thus, treatment of adenosine (29, Scheme 5) with TrCl in pyridine containing 4-dimethylaminopyridine (DMAP) at 80 C for 2-3 days afforded a mixture of 5 -O-trityl-N -trityladenosine(30),3, 5 -di-0-trityl-N -trityladenosine(31),2, 5 -di-O-trityl-N -trityl-adenosine (32), and N N -ditrityladenine (33). These compounds were separated on a silica gel column, and the desired nucleoside 31, was obtained in crystalline form in 20% yield. Further tritylation of 30 afforded additional amount of 31 increasing the total yield of 31 up to 34%. 

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