Patent GB-1243214-A (GB)
Title: Nucleoside 6'-phosphonic acids and the corresponding phosphonates
IPC: C07F9/53
Filed: 1968-07-11
Abstract: 1,243,214. Nucleoside-6<SP>1</SP>-phosphonic acids and derivatives thereof. SYNTEX CORP. 11 July, 1968 [18 July'1967; 29 Feb., 1968] No. 3377/71. Divided out of 1,243,213. Heading C2C. The invention comprises nucleoside phosphonic acid derivatives of the, formulµ wherein R<SP>12</SP> is a substituted or unsubstituted purine or pyrimidine base radical; R<SP>13</SP>, R<SP>13</SP>', R<SP>14</SP> and R<SP>14</SP>' each is hydrogen, OH, alkoxy or acyloxy or R<SP>13</SP> and R<SP>14</SP> together is an acetal or ketal group,-Z<SP>3</SP> and Z<SP>4</SP> each are the group OH, OR<SP>5</SP>, SR<SP>6</SP> _ or NR<SP>7</SP>'R<SP>8</SP>' in which each of R<SP>5</SP> and R<SP>6</SP> is G 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 6- C 12  aryl or aryl substituted by one or more halo, nitro, alkoxy, or dialkylamino substituents in the aromatic ring the term #aryl" including benzyl, and each of R<SP>7</SP>' and R<SP>8</SP>' is C1-C6 alkyl, or Z<SP>3</SP> and Z<SP>4</SP> together are the group wherein R<SP>9</SP>' is arylene. The compounds.may be obtained by the methods disclosed in Specification 1,243,213, said methods involving the reaction of a nucleoside 51-aldehyde (XX) with a phosphorylated phosphonium ylid (XXI) and being indicated by the following reaction sequence wherein each of Z<SP>1</SP>" and Z<SP>2</SP>" is the group OR<SP>5</SP>, SR<SP>6</SP> Formula I, and, or NR<SP>7'</SP>R<SP>8</SP>' in which R<SP>5</SP>, R<SP>6</SP>, R<SP>7</SP>' and R<SP>8</SP>' are as defined above or Z<SP>1</SP>" and Z<SP>2</SP>" together are the group in which R<SP>9</SP>' is arylene, R<SP>1</SP>, R<SP>2</SP>, and R<SP>3</SP> are C i - C<SP>6</SP> alkyl, or aryl or substituted aryl, or R<SP>1</SP>, R<SP>2</SP> and R<SP>3</SP> together are tri-N-piperidyl, tri-N- morpholinyl or tricyclohexyl and R<SP>10</SP> is the radical of a nucleoside aldehyde R<SP>10</SP>CHO of the formula  wherein R<SP>12</SP>, R<SP>13</SP> ,  R<SP>14</SP> ,  R<SP>13</SP>' and B<SP>14</SP>' are as defined above. The product (XXII) can be catalytically hydrogenated at room temperature to form (XXIII) or can be reduced by treatment with diimide at room temperature in an inert solvent to form (XXIII). Each of the Z<SP>1</SP>" and Z<SP>2</SP>" groups in the latter can then be removed in one or more steps by hydrolysis, hydrogenolysis, anionic dealkylation, enzymatic action or cornbinations thereof to form (XXV). Alternatively (XXII) can be converted to (XXIV) by hydrolysis, hydrogenolysis, anionic dealkylation enzymatic action or combinations thereof (as above) and (XXIV) can then be converted to (XXV) by catalytic hydrogenation or diimide reduction as above. The products of the formula (XXII) and (XXIV) are identical to products represented by (XVI) and (XVII) and the products represented by (XXIII) and (XXV) are identical to the compounds represented by (XVIII) and (XIX). The nucleoside 6<SP>1</SP>-phosphonic acids may be converted to cyclic 3<SP>1</SP>,6<SP>1</SP>- phosphonates by treating with a dehydrating agent, e.g. a carbodiimide, in a basic solvent such as pyridine.