Efficient synthesis of nicotinamide mononucleotide

1. A process for the preparation of nicotinamide mononucleotide having formula (I):

or a salt thereof, wherein the process comprises the steps of:

(i) reacting nicotinamide riboside having formula (II):

 with a ketalization reagent that is R 1 R 2 C(OR 3 )(OR 4 ) or R 1 R 2 C═O, wherein R 1 -R 4 are independently C 1 -C 6 alkyl in a solvent in the presence of an acid catalyst, to form a compound of formula (III):

(ii) isolating the compound of formula (III),

(iii) reacting the compound of formula (III) with a mixture of POCl 3 and PO(OR 5 ) 3 , wherein R 5 is C 1 -C 6 alkyl, followed by treatment with water to form a compound of formula (IV):

 or a salt thereof,

(iv) isolating the compound of formula (IV),

(v) reacting the compound of formula (IV) with an acid catalyst in a solvent or mixture of solvents to provide nicotinamide mononucleotide, and

(vi) isolating nicotinamide mononucleotide.

2. The process of claim 1 , wherein the ketalization reagent is (CH 3 ) 2 C(OCH 3 ) 2 .

3. The process of claim 1 , wherein the solvent in step (i) is CH 3 CN.

4. The process of claim 3 , wherein the acid catalyst in step (i) is H 2 SO 4 .

5. The process of claim 1 , wherein the solvent in step (v) is a mixture of dichloromethane and water.

6. The process of claim 1 , wherein the solvent in step (v) is methanol.

7. The process of claim 1 , wherein the acid catalyst in step (v) is trifluoroacetic acid.

8. The process of claim 1 , wherein the acid catalyst in step (v) is hydrochloric acid.

9. A process for the preparation of a compound of formula (IV):

or a salt thereof,

wherein R 1 and R 2 are independently C 1 -C 6 alkyl,

wherein the process comprises the step of reacting a compound of formula (III):

 with a mixture of POCl 3 and PO(OR 5 ) 3 , wherein R 5 is C 1 -C 6 alkyl, followed by treatment with water to form a compound of formula (IV).