Process for producing coelenteramide or an analog thereof
A process for producing coelenteramide or its analog in a high yield has been desired. The invention provides a process for producing di-O-methylcoelenteramide or its analog of formula (3) which comprises reacting O-methylcoelenteramine or its analog with 4-methoxyphenylacetyl halide or its analog. The invention also provides a process for producing coelenteramide or its analog, which comprises demethylation of di-O-methylcoelenteramide or its analog.
1. A process for producing a compound represented by formula (3):
wherein,
R 1 represents an alkyl having 1 to 3 carbon atoms or an arylalkyl having 7 to 10 carbon atoms,
R 3 represents (i) an alkyl having 1 to 7 carbon atoms which may optionally be substituted with an alicyclic group, (ii) an alicyclic group or (iii) an arylalkyl having 7 to 10 carbon atoms, and,
R 4 represents an alkyl having 1 to 3 carbon atoms or an arylalkyl having 7 to 10 carbon atoms, which comprises reacting a compound represented by formula (1):
wherein R 1 and R 3 are as defined above, and, R 2 is amino
with a compound represented by formula (2):
wherein X is a splitting-off group and R 4 is as defined above.
2. The process according to claim 1 , wherein in formula (1), R 1 is methyl, ethyl, propyl, isopropyl, benzyl, α-methylbenzyl, phenethyl, 3-phenylpropyl or 4-phenylbutyl.
3. The process according to claim 1 , wherein in formula (1), R 3 is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, t-butyl, pentyl, isopentyl, neopentyl, t-pentyl, hexyl, heptyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, α-methylbenzyl, phenethyl, 3-phenylpropyl or 4-phenylbutyl.
4. The process according to claim 1 , wherein in formula (2), X is chlorine, bromine, iodine, methanesulfonyloxy, benzenesulfonyloxy, or toluenesulfonyloxy.
5. The process according to claim 1 , wherein in formula (2), R 4 is methyl, ethyl, propyl, isopropyl, benzyl, α-methylbenzyl, phenethyl, 3-phenylpropyl or 4-phenylbutyl.
6. The process according to claim 1 , wherein the compound represented by formula (1) is selected from the group consisting of:
7. The process according to claim 1 , wherein the compound represented by formula (2) is selected from the group consisting of:
8. A process for producing the compound:
which comprises reacting the compound:
with the compound:
9. A process for producing a compound represented by formula (4):
wherein R 3 represents (i) an alkyl having 1 to 7 carbon atoms which may optionally be substituted with an alicyclic group, (ii) an alicyclic group or (iii) an arylalkyl having 7 to 10 carbon atoms,
which comprises splitting-off a group shown by R 1 wherein R 1 represents an alkyl having 1 to 3 carbon atoms or an arylalkyl having 7 to 10 carbon atoms and a group shown by R 4 wherein R 4 represents an alkyl having 1 to 3 carbon atoms or an arylalkyl having 7 to 10 carbon atoms from a compound represented by formula (3):
wherein R 1 , R 3 and R 4 are as defined above.
10. The process according to claim 9 , wherein in formula (3), R 1 is methyl, ethyl, propyl, isopropyl, benzyl, α-methylbenzyl, phenethyl, 3-phenylpropyl or 4-phenylbutyl.
11. The process according to claim 9 , wherein in formula (3), R 3 is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, t-butyl, pentyl, isopentyl, neopentyl, t-pentyl, hexyl, heptyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, α-methylbenzyl, phenethyl, 3-phenylpropyl or 4-phenylbutyl.
12. The process according to claim 9 , wherein in formula (3), R 4 is methyl, ethyl, propyl, isopropyl, benzyl, α-methylbenzyl, phenethyl, 3-phenylpropyl or 4-phenylbutyl.
13. The process according to claim 9 , wherein the compound represented by formula (3) is selected from the group consisting of:
14. A process for producing the compound:
which comprises splitting-off methyl from the compound: