Process for the preparation of 2'-O-alkyl guanosine and related compounds

Claim 2

A process for preparing 2'-O-substituted guanosine comprising the steps of: a) reacting 2,6-diaminopurine riboside with a base of sufficient strength to remove a proton from the 2'-hydroxyl or 3'-hydroxyl of 2,6-diaminopurine riboside, and with a compound having the formula R--L wherein R is an aliphatic or alicyclic group and L is a leaving group, to form 2'-O-substituted-2,6-diaminopurine riboside and 3'-O-substituted-2,6-diaminopurine riboside wherein said substituent is said aliphatic or alicylic group; and b) deaminating said 2'-O-substituted-2,6-diaminopurine riboside to yield said 2'-O-substituted guanosine; and c) recovering said 2'-O-substituted guanosine.

Claim 3

The process of claim 1 further comprising: separating said 2'-O-substituted-2,6-substituted diaminopurine riboside from said 3'-O-2,6-diaminopurine riboside.

Claim 4

The process of claim 1 wherein said 2'-O-substituted-2,6-diaminopurine riboside is deaminated with adenosine deaminase.

Claim 5

The process of claim 1 wherein said base is sodium hydride.

Claim 6

The process of claim 1 wherein said 2'-O-substituted-2,6-diaminopurine riboside is physically separated from said 3'-O-substituted-2,6-diaminopurine riboside by crystallization or chromatography.

Claim 7

A process for preparing 2'-O-substituted-2,6-diaminopurine riboside, 3'-O-substituted-2,6-diaminopurine riboside, and 2',3'-di-O-substituted-2,6-diaminopurine riboside comprising the steps of: a) reacting 2,6-diaminopurine riboside with a base of sufficient strength to remove a proton from the 2'- or 3'-hydroxyl of 2,6-diaminopurine riboside and with a compound having the formula R--L wherein R is an aliphatic or alicylic group and L is a leaving group, to form at least one compound selected from the group consisting of 2'-O-substituted-2,6-diamino-purine riboside, 3'-O-substituted-2,6-diamino-purine riboside, and 2',3'-di-O-substituted-2,6-diaminopurine riboside wherein said substituent is an aliphatic or an alicyclic group; and b) isolating one of said substituted-2,6-diaminopurine ribosides.

Claim 8

A process for preparing 2'-O-substituted-2,6-diaminopurine riboside, 3'-O-substituted-2,6-diaminopurine riboside, and 2',3'-di-O-substituted-2,6-diaminopurine riboside comprising the steps of: a) reacting 2,6-diaminopurine riboside with a base of sufficient strength to remove a proton from the 2'- or 3'-hydroxyl of 2,6-diaminopurine riboside and with a compound having the formula R--L wherein R is an aliphatic or alicylic group and L is a leaving group, to form at least one compound selected from the group consisting of 2'-O-substituted-2,6-diamino-purine riboside, 3'-O-substituted-2,6-diamino-purine riboside, and 2',3'-di-O-substituted-2,6-diaminopurine riboside wherein said substituent is an aliphatic or an alicyclic group; and b) isolating one of said substituted-2,6-diaminopurine ribosides.

Claim 9

The process of claim 6 further comprising adding sufficient compound R--L and base to form at least two of the compounds selected from the group consisting of 2'-O-substituted-2,6-diaminopurine riboside, 3'-O-substituted-2,6-diaminopurine riboside, and 2',3'-di-O-substituted-2,6-diaminopurine riboside; and separating out at least one of said substituted 2,6-diaminopurine riboside compounds.

Claim 10

The process of claim 7 further comprising separating out at least one specific substituted-2,6-diaminopurine riboside by crystallization.

Claim 11

The process of claim 7 further comprising separating out at least one specific substituted-2,6-diaminopurine riboside by chromatography.

Claim 12

The process of claim 1 wherein said aliphatic or alicyclic group is selected from the group consisting of C 1-20 straight chain alkyl, C 1-20 branched alkyl, C 1-20 straight chain alkenyl, C 1-20 branched chain alkenyl, C 1-20 straight chain alkynyl, and C 1-20 branched chain alkynyl.

Claim 13

The process of claim 10 wherein said aliphatic or alicylic group bears a substituent selected from the group consisting of halogen, hydroxyl, thiol, keto, carboxyl, nitrate, nitro, nitroso, nitrile, trifluoromethyl, trifluoromethoxy, O-alkyl, S-alkyl, NH-alkyl, N-dialkyl, O-aralkyl, S-aralkyl, NH-aralkyl, amino, azido, hydrazino, hydroxylamino, isocyanato, sulfoxide, sulfone, sulfide, disulfide, silyl, heterocyclic, alicylic, intercalators, polyamines, polyamides, polyethylene glycols, and polyethers.

Claim 14

The process of claim 10 wherein said aliphatic or alicyclic group is substituted with a carbocylic group.

Claim 15

The process of claim 10 wherein said aliphatic or alicyclic group is substituted with a reporter molecule.