Suzuki–Miyaura coupling for general synthesis of dehydrocoelenterazine applicable for 6-position analogs directing toward bioluminescence studies

Synthetic Routes to Coelenterazine and Other Imidazo[1,2‐a]pyrazin‐3‐one Luciferins: Essential Tools for Bioluminescence‐Based Investigations

“…Finally, from the thioacetal 91 , a deprotonation followed by the addition of dimethylformamide led to compound 92 . Protection of the aldehyde moiety and hydrolysis of the thioacetal group of 93 gave glyoxal derivative 94 which was used to prepare a methoxylated analogue of coelenterazine ( 7 ) 85. A far more complex preparation of an isomer of this glyoxal was also used for the preparation of the 13 C‐labeled methoxylated coelenterazine analogue 86.…”

“…With this building block, the triflate derivative 141 was made and, prior to a Suzuki–Miyaura reaction, the tosyl protecting group of compound 141 could be hydrolyzed (in concentrated sulfuric acid at 0 °C) without affecting its remarkably stable triflate function 104. From the resulting compound 142 , many Suzuki–Miyaura coupling reaction were achieved, which led to many analogues of coelenterazine 85. 104 Moreover, the preparation of the imidazo[1,2‐ a ]pyrazine 6‐ O ‐triflate 143 could be carried out by a condensation reaction between 142 and the glyoxal 68 .…”

“…A subsequent Suzuki–Miyaura coupling reaction with the rather more reactive triflate 143 was found possible although along with an unexpected oxidation which led to dehydrocoelenterazine analogues such as the methyl ether 144 . Remarkably, whereas the O ‐tosyl equivalent of the triflate ester 145 did not survive the basic conditions of this coupling reaction, the oxidized O ‐tosyl derivative 146 turned out to be far more stable and its coupling with 4‐methoxyphenylboronic acid gave an excellent yield of the methyl ether of dehydrocoelenterazine 144 85…”

Groupware requirements evolution patterns

“…An organic solution containing TODGA (N,N,N',N'-tetra-n-octyl diglycolamide) (0.2 mol/L) and 5 vol-% 1-octanol in TPH was used as solvent. 31 The TODGA molecule is known to efficiently extract trivalent lanthanides and actinides from moderate to high nitric acid concentrations. 32,33 A weighted amount of the hydrophilic ligand was dissolved in an aqueous NH 4 NO 3 (0.5 mol/L) solution followed by pH adjustment (HNO 3 or NaOH) and addition of traces of 241 Am(III) and 152 Eu(III).…”

“…31 Reaction of 5-O-triflyl-3-benzyl-2-aminopyrazine with different arylboronic acids afforded the coupled products in good yields (Scheme 2.15) showing triflate to be a suitable leaving group. However, the procedure requires a high load (up to 10 mol%) of palladium catalyst.…”