Methods for producing (6S,15S)-3,8,13,18-tetraazaicosane-6,15-diol

1. A method of producing Compound 1 or a salt thereof,

comprising the steps of:

(a) reacting a compound of Formula (I),

wherein each PG is an amino protecting group,

with a compound of Formula (II),

wherein X is a leaving group;

thereby producing a compound of Formula (III),

(b) reacting the compound of Formula (III) with a reducing agent, thereby producing a compound of Formula (IV),

(c) reacting the compound of Formula (IV) with an acetylating agent thereby producing a compound of Formula (V),

(d) reacting the compound of Formula (V) with a reducing agent, thereby producing a compound of Formula (VI),

and

(e) deprotecting the compound of Formula (VI), optionally in the presence of an acid, thereby producing Compound 1 or a salt thereof.

2. The method of claim 1 , wherein PG is benzyl or substituted benzyl.

3. The method of claim 2 , wherein PG is benzyl, 4-methoxybenzyl or 3,4-dimethoxybenzyl.

4. The method of claim 3 , wherein PG is benzyl.

5. The method of claim 2 , wherein in step (e), the compound of Formula (VI) is deprotected by hydrogenolysis.

6. The method of claim 4 , further comprising the step of reacting 1,4-diaminobutane with benzaldehyde under reducing conditions, thereby producing the compound of Formula (I).

7. The method of claim 1 , wherein the reducing agent of step (b) is lithium aluminum hydride.

8. The method of claim 1 , wherein the acetylating agent is acetic anhydride.

9. The method of claim 1 , wherein the reducing agent of step (d) is lithium aluminum hydride.

10. The method of claim 1 , wherein PG is benzyl; the reducing agent of step (b) and the reducing agent of step (d) are both lithium aluminum hydride; and the acetylating agent is acetic anhydride.

11. The method of claim 1 , wherein step (a) is conducted in the presence of a base.

12. The method of claim 11 , wherein the base is K 2 CO 3 , NaHCO 3 or diisopropylethylamine.

13. The method of claim 11 , where step (a) is conducted in a polar organic solvent.

14. The method of claim 13 , wherein the solvent is ethanol, N,N-dimethylformamide, or acetone.

15. The method of claim 1 , wherein step (a) is conducted in an ethanol solution of sodium bicarbonate.

16. The method of claim 1 , wherein the reducing agent in step (b) is lithium aluminum hydride or Raney nickel and ammonia.

17. The method of claim 1 , wherein step (b) is conducted in tetrahydrofuran or methanolic ammonia.