Adenosine cyclic 3 ,5 -phosphate preparation

The reaction probably proceeds through the formation of an imino analogue of mixed anhydrides by nucleophilic displacement of cyanide during the phosphate activation. Cyanogen bromide was found to be more effective than DISN in this transformation. Since higher yields were obtained in the preparation of the cyclic phosphate from 3 -adenosinc phosphate than from 2/-adenosine phosphate, the authors suggested the formation of an activated... 

The most widely used imidazole intermediates for the preparation of 2-substituted adenosines are 5-aminoimidazole-4-carboximidamide derivatives. For example, 5-amino-l-()S-D-ribofura-nosyl)imidazole-4-carboximidamide 3, 5 -cyclic phosphate can be treated with various reagents under relatively mild conditions to give directly 2-substituted cAMP derivatives, e.g. 1 and 2. ... 

Similar use has been made of trifluoroacetic anhydride in the preparation of the cyclic 2,3-phosphate of adenosine from adenosine 2-phosphate the latter appears to be converted into the unsymmetrical anhydride, which then acts as an internal phosphorylating agent toward the C-3-hydroxyl group. Treatment of the product with ethanolic ammonia removed the... 

Ribonucleoside 2 3 -cyclic phosphate have been prepared by phosphorylation of the 5 -0-acyl derivatives of adenosine and uridine with P -diphenyl P -morpholino pyrophosphorochloridate (63), followed by treatment with dilute ammonium hydroxide. An interesting innovation... 

The independent form can be converted into the dependent form by a difiFerent mechanism. It has been found that addition of calcium ions to certain glycogen synthetase preparations produces a conversion of the independent into the dependent form. This conversion does not involve ATP, and is not aflFected by adenosine 3 5 -cyclic phosphate it requires a protein similar to that involved in the activation of inactive phosphorylase b kinase by Ca ". Thus, calcium appears to exert an effect on the regulation of glycogen synthetase, and it is hypothesized that the inactivation of muscle glycogen synthetase after muscle contraction may be caused by this mechanism, mediated by an alteration of intracellular levels of Ca +. 

As usual, standard syntheses of nucleotides are not included in this survey. Using adenosine 5 -[(i )- 0, 0, 0]phosphate, it has been shown that the conversion of adenosine 5 -phosphate to cyclic AMP and the enzymatic hydrolysis of the latter to the former both occur with retention of configuration at phosphorus. Cyclic AMP can be used to prepare 2 -0-substituted adenosine derivatives 2 -0-succinyl adenosine was synthesized by acylation followed by enzymatic dephosphorylation on equilibration the 3 -0-succinyl isomer was slightly favoured (54%). ... 

In the area of cyclic phosphates, adenosine 3, 5 -cyclic phosphorofluoridate has been prepared it was shown to undergo facile conversion to adenosine 2, 3 -cyclic phosphate. A photolabile 3, 5 -cyclic phosphotriester of adenosine has been described,as have 3, 5 -cyclic phosphotriesters and phosphoramidates of 8-chloroadenosine. ... 

Alkyl halides are even less reactive than acyl halides, as indicated by the compilation of reaction rates of thiolate anions with various types of alkyl halides (282). Nevertheless, potentially useful affinity labels have been synthesized with alkyl halide substituents and have been shown to specifically inactivate several enzymes, albeit slowly the low reactivity of the alkyl halides may minimize nonspecific reaction. Adenosine 5 -(2-bromoethyl)phosphate has been characterized and reported to inactivate NAD -dependent isocitrate dehydrogenase (283). The 2 - and 3 -(2-bromoethyl)-AMP labels have also been synthesized, and model reactions of the bromoethyl-AMPs with cysteine, lysine, histidine, and tyrosine have been studied (284). More recently, esters of adenosine 5 -monophosphate have been prepared with ethyl, propyl, or hexyl moieties and bromo or chloro substituents at the w position (285). Yeast alcohol dehydrogenase exhibited enhanced inactivation by the hexyl derivative, but inactivation rates of other dehydrogenases were unremarkable. Two iodopropyl derivatives of cAMP have been described, namely, 1, A -(3-iodopropyleno)adenosine 3, 5 -cyclic monophosphate and 3 -0-(2-iodo-3-hydroxypropyl)adenosine 3, 5 -cyclic monophosphate the latter inactivates cAMP phosphodiesterase from human platelets, with a pseudo-first-order rate constant of 0.147 hr" (286). 

Two publications on the higher ketose mono- and bis-phosphates in rat-liver extracts have described their detection and estimation by colorimetry and enzymic assay,and the synthesis of octulose 1,8-bisphosphates using muscle aldolase. A stereospecific synthesis of adenosine 3, 5 -cyclic phosphothioate has appeared/ Standard condensation methods have been used to synthesize the 5 -O-(Taminoethane-phosphonyl) nucleosides (21) and (22). The compounds were shown to be inert to the action of alkaline phosphatase and are poor substrates for 5 -nucleotidase. The selenophosphates (23) and (24) have been prepared.Phosphorylation of nucleosides using dibenzyl hydrogen phosphate,... 

The C-3 deuterated 5-phosphate 51 was an intermediate in the preparation of D-erythro-[3- Jitnidazole glycerol phosphate from diacetoneglucose. Several 2-0-phosphorylated 1,4-anhydropentitols, e.g. compound 52, 2 -0-methyl-adenosine 3, 5 -cyclic monophosphate, 1,5-anhydroxylitol- and l,5-anhydro-E>-arabinitol-2,3,4-phosphate, D-mannopyranose 1.4,6-triphosphate, and a series of polyphoqihorylated D-galacmsides, such as conqwunds 53, have been synthesized by conventional procedures for use in Inological studies. 

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