[Molecules: 21] [Related articles/posters: 048 018 059 066 052 ]

Synthesis of 3,5-disubstituted 2-aminopyrazines by palladium-mediated cross-couplings and its use for preparing chemi- and/or bio-luminescent compounds

Hideshi Nakamura, Daisuke Takeuchi, Mihoko Aizawa, Chun Wu and Akio Murai

Introduction

3,6,8-Trisubstituted imidazopyrazine-2-ones are widely distributed in marine organisms and in some cases are used as bioluminescent substances such as a jellyfish Aequorea aequorea and a crustacean Cypridina (Vargula) hirgendorfii. These compounds are also chemiluminescent and utilized to detect chemicals such as Ca²⁺ or active oxygen species such as superoxide. We have investigated convergent synthesis in order to prepare imidazopyrazinones with different luminescent properties such as colour of luminescence.

Since 5-aryl-3-substituted-2-aminopyrazines have been used to prepare chemi- and/or bio-luminescent imidazopyrazinones, we have developed a new approach to synthesize 3,5-disubstituted 2-aminopyrazines having conjugated chromophores from commercially available 2-aminopyrazine by several steps including palladium-mediated cross-coupling as a key reaction.

Results and discussion

I Synthesis of 3,5-disubstituted 2-aminopyrazines from 2-aminopyrazine.

1. Alkylation of 2-aminopyrazine with organolithium
2. Arylation of 3-bromo and 3,5-dibromo-2-aminopyrazine
3. Alkynylation of 3-bromo and 3,5-dibromo-2-aminopyrazine

II Synthesis of chemi- and/or bioluminescent imidazopyrazinones

1. Synthesis of Coelenterazine
2. Synthesis of Cypridina luciferin analogue
3. Synthesis and chmemiluminescence of imidazopyrazinones

Conclusion