Processes for the production of tryptamines
Disclosed herein are prokaryotic and eukaryotic microbes, including E. coli and S. cerevisiae , genetically altered to biosynthesize tryptamine and tryptamine derivatives. The microbes of the disclosure may be engineered to contain plasmids and stable gene integrations containing sufficient genetic information for conversion of an anthranilate or an indole to a tryptamine. The fermentative production of substituted tryptamines in a whole-cell biocatalyst may be useful for cost effective production of these compounds for therapeutic use.
1. A compound of Formula (I):
or a pharmaceutically acceptable salt thereof, wherein,
R 1 is selected from H and optionally substituted C 1-5 alkyl;
R 2 is selected from optionally substituted linear C 3-5 alkyl; and
R 4 , R 5 , R 6 , and R 7 are independently selected from H and —O(P═O)(OH) 2 , wherein at least one of R 4 , R 5 , R 6 , and R 7 is —O(P═O)(OH) 2 .
2. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 1 is H.
3. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 1 is C 1-5 alkyl.
4. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 1 is C 3 alkyl.
5. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 4 is —O(P═O)(OH) 2 and R 5 , R 6 , and R 7 are H.
6. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 5 is —O(P═O)(OH) 2 and R 4 , R 6 , and R 7 are H.
7. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 6 is —O(P═O)(OH) 2 and R 4 , R 5 , and R 7 are H.
8. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 7 is —O(P═O)(OH) 2 and R 4 , R 5 , and R 6 are H.
9. A compound selected from the group consisting of:
or a pharmaceutically acceptable salt of any one thereof.
10. The compound of claim 9 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
11. The compound of claim 9 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
12. The compound of claim 9 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
13. The compound of claim 9 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
14. The compound of claim 9 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
15. The compound of claim 9 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
16. The compound of claim 9 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
17. The compound of claim 9 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
18. The compound of claim 9 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
19. The compound of claim 9 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
20. The compound of claim 9 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
21. A pharmaceutical composition, comprising a compound of Formula (I):
or a pharmaceutically acceptable salt thereof, wherein,
R 1 is selected from H and C 1-5 alkyl;
R 2 is C 3-5 alkyl; and
R 4 , R 5 , R 6 , and R 7 are independently selected from H and —O(P═O)(OH) 2 , wherein at least one of R 4 , R 5 , R 6 , and R 7 is —O(P═O)(OH) 2 .
22. The pharmaceutical composition of claim 21 , wherein one of R 5 , R 6 , and R 7 is —O(P═O)(OH) 2 .
23. The pharmaceutical composition of claim 21 , wherein R 1 is H or C 3 alkyl.
24. The pharmaceutical composition of claim 21 , wherein R 2 is C 3 alkyl.
25. A method of improving perception and mood in a human subject in need thereof, comprising administering to the human subject in need thereof a compound of Formula (I):
or a pharmaceutically acceptable salt thereof, wherein,
R 1 is selected from H and C 1-5 alkyl;
R 2 is C 3-5 alkyl; and
R 4 , R 5 , R 6 , and R 7 are independently selected from H and —O(P═O)(OH) 2 , wherein at least one of R 4 , R 5 , R 6 , and R 7 is —O(P═O)(OH) 2 .