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Under an argon atmosphere, 2-amino-3-benzyl-5-(4-hydroxyphenyl)pyrazine (coelenteramine) (c-5) (prepared by the method described in Adamczyk M. et al., Org. Prep. Proced. Int., 33, 477-485 (2001)) (199 mg, 718 μmol) was dissolved in pyridine (1.5 mL) and to this was added 4-(dimethylamino)pyridine (9.0 mg, 74 μmol) and cooled to 0° C. To this was added p-toluenesulfonyl chloride (410 mg, 2.15 mmol) and stirred for 2 h after warming to room temperature. To this were added 2 M hydrochloric acid and dichloromethane to stop the reaction and, after separating the aqueous layer and organic layer, it was extracted 3 times with dichloromethane and was washed with saturated aqueous solution of sodium sulfate and then dried over anhydrous sodium sulfate. After removing anhydrous sodium sulfate by filtration, the filtrate was concentrated under reduced pressure with a rotary evaporator. The residue was dissolved in methanol (5 mL) and to this was added 10% (w/v) aqueous, solution of sodium hydroxide (1.2 mL) while stirring at room temperature and stirred at 65° C. for 30 min. After cooling to room temperature, to this was added 2 M hydrochloric acid to stop reaction and extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. After removing anhydrous sodium sulfate by filtration, the filtrate was concentrated under reduced pressure with a rotary evaporator. The residue was purified by column chromatography (23 g, n-hexane/ethyl acetate=3/2) to give 3-benzyl-5-(4-hydroxyphenyl)-2-[(4-methylphenyl)sulfonylamino]pyrazine (coelentera-p-tosylamide) (c-35) as a yellow solid (155 mg, 37.1% (2 steps)). Rf=0.25 (n-hexane/ethyl acetate=3/2). Mp. 181-182.5° C. UV (MeOH) λmax (log ε) 336.5 (4.10), 291.5 (4.26), 277 (4.27). UV (pH 7.4 PB) λmax (log ε) 351 (4.14), 282.5 (4.37). 1H NMR (400 MHz, DMSO-d6) δ 2.36 (s, 3H), 4.27 (s, 2H), 6.81 (d, J=8.7 Hz, 2H), 7.17-7.24 (m, 1H), 7.25-7.32 (m, 4H), 7.36 (d, J=7.6 Hz, 2H), 7.79 (t, J=8.7 Hz, 4H), 8.53 (s, 1H), 9.77 (s, 1H), 10.74 (s, 1H). IR (KBr, cm−1) 474, 525, 546, 567, 610, 667, 698, 743, 816, 839, 876, 941, 1088, 1148, 1165, 1215, 1269, 1321, 1364, 1404, 1447, 1495, 1516, 1593, 1609, 3283. HRMS (FAB+) m/z 432.1382 (M+H, C24H22N3O3S requires 432.1382).

1. temperatureafter warming to room temperature
2. customthe reaction
3. customafter separating the aqueous layer and organic layer, it
4. extractionwas extracted 3 times with dichloromethane
5. washwas washed with saturated aqueous solution of sodium sulfate
6. dry with materialdried over anhydrous sodium sulfate
7. customAfter removing anhydrous sodium sulfate
8. filtrationby filtration
9. concentrationthe filtrate was concentrated under reduced pressure with a rotary evaporator
10. dissolutionThe residue was dissolved in methanol (5 mL)
11. additionto this was added 10% (w/v) aqueous
12. stirringsolution of sodium hydroxide (1.2 mL) while stirring at room temperature
13. stirringstirred at 65° C. for 30 min
14. temperatureAfter cooling to room temperature
15. additionto this was added 2 M hydrochloric acid
16. customreaction
17. extractionextracted 3 times with ethyl acetate
18. washThe organic layer was washed with saturated brine
19. dry with materialdried over anhydrous sodium sulfate
20. customAfter removing anhydrous sodium sulfate
21. filtrationby filtration
22. concentrationthe filtrate was concentrated under reduced pressure with a rotary evaporator
23. customThe residue was purified by column chromatography (23 g, n-hexane/ethyl acetate=3/2)