Asymmetric Total Syntheses and Structure Revisions of Eurotiumide A and Eurotiumide B, and Their Evaluation as Natural Fluorescent Probes

Abstract

Asymmetric total syntheses and structure revisions of dihydroisocoumarin‐type natural products, eurotiumide A and eurotiumide B have been described. The key features of these total syntheses are the asymmetric Shi epoxidation, regio‐ and stereoselective epoxide opening, C1 insertion/lactonization cascade reaction for constructing the 4‐methoxyisochroman‐1‐one skeleton. We confirmed the structures and configurations of eurotiumide A and B on the basis of X‐ray crystallographic analysis of the key intermediate and revealed that eurotiumide A and B have cis and trans configurations at the H3/H4 positions, which indicates the opposite relationship of the stereochemistry with respect to the previous report. Their absolute configurations were also determined. These natural products are highly fluorescent in several solvents with large Stokes shifts involving the excited‐state intramolecular proton transfer mechanism, which is supported by time‐dependent density functional theory. Eurotiumide A also displays fluorescence in Bacillus cereus.

N‐Formylsaccharin as a CO Source: Applications and Recent Developments

“…The acyl fluorides ( 15 ) readily transformed into various carboxylic acid derivatives ( 16 ) such as carboxylic acid, esters, thioesters, and amides in a one‐pot procedure (Scheme 9). In 2018, Nakayama and his colleagues apply acyl fluorides as a key intermediate during the reporting of the asymmetric total syntheses and structure revisions of eurotiumide A and eurotiumide B [28] . Subsequently, they constructed cis‐4‐methoxy isochromamide‐1‐one skeleton ( 18 a – b ) via a C1 insertion/lactonization cascade reaction (Scheme 10).…”

Annulations with Butenolides and Phthalides: New Entries to Isocoumarins, 3,4-Dihydroisocoumarins, and Benzofurans

“…1 Nakayama and co-workers recently reported a synthesis and structure revision. 35 In view of the urgent need to identify environmentally benign antifouling agents to replace toxic, metal-based antifouling agents, 36 we sought to develop a practical synthetic route. The route needed to be efficient and scalable to provide a useful antifouling agent.…”

Synthesis and Antimicrobial Evaluation of Side-Chain Derivatives based on Eurotiumide A

“…In particular, because there is a chance that modification of the side chain of the aromatic ring could improve antimicrobial activity and the spectrum, a structure-activity relationship study of the substituent effect of the aromatic ring is essential for discovering promising candidates for antimicrobial agents. Recently, we reported the first asymmetric total syntheses of (−)-eurotiumide A (1) and (+)-eurotiumide B and revised their reported structures [24]. In our synthetic route, the prenyl side chain of the aromatic ring was introduced in the late stage by the Stille coupling reaction with the key intermediate 2.…”

“…Based on our previous results, we considered that a number of derivatives of 1, which have a variety of kinds of side-chain moiety, could be obtained from the common intermediate 2 and non-substituted compound 3 in the late stage of synthesis ( Figure 1). In this work, as part of our continuing research [24,25], we constructed a chemical library of the side-chain derivatives of eurotiumide A (1) to elucidate the effects of the side chains of the aromatic rings and to develop antimicrobial agents against methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (both Gram-positive bacteria), as well as Porphyromonas gingivalis (a Gram-negative bacterium).…”