Total Synthesis of Benzofuran-Based Aspergillusene B via Halogenative Aromatization of Enones

Abstract

A novel "non-aromatic pool" synthetic strategy for the synthesis of benzofuran-based natural products via oxidative haloaromatization of enones is reported. This approach is successfully applied in the first total synthesis of the natural product aspergillusene B. In comparison with a separately executed "aromatic pool" synthesis, the "non-aromatic pool" protocol demonstrates equivalent efficiency but offers a much higher degree of modularity.

Marine natural products

“…287 Known terrestrial avone chrysin 796 was isolated from Chaetomium globosum as a new MNP. 288 Completed total syntheses of fungal metabolites included those of wickerol B, 289 (+)-penostatin A and (+)-penostatin C, 290 versicotides A-C, 291 cladosin B, 292 spirograterpene A, 293 nafuredin B, 294 chondristerins I and J, 295 aspergillusene B 296 and yicathins B and C. 297 Several known compounds including nortryptoquivaline, chevalone C, tryptoquivaline H, scalin A, epi-neoscalin A and epi-scalin A potentiated the cytotoxic effect of doxorubicin in lung cancer cells 298 and the lipopeptidyl benzophenone, asperphenin A, inhibited colon cancer cell growth through G2/M cell cycle arrest followed by apoptosis. Asperphenin A suppressed tumour growth in vivo in a colon cancer xenogra model without obvious toxicity and exhibited a combination effect with the topoisomerase I inhibitor, irinotecan.…”

“…287 Known terrestrial flavone chrysin 796 was isolated from Chaetomium globosum as a new MNP. 288 Completed total syntheses of fungal metabolites included those of wickerol B, 289 (+)-penostatin A and (+)-penostatin C, 290 versicotides A–C, 291 cladosin B, 292 spirograterpene A, 293 nafuredin B, 294 chondristerins I and J, 295 aspergillusene B 296 and yicathins B and C. 297…”

Iron‐Catalyzed Gamma‐Gamma Dimerization of Siloxydienes

“…[28] In contrast to the literature route, this strategy utilizes a complementary non-aromatic core which may provide advantageous opportunities for diversification and avoids transformations such as electrophilic aromatic substitution that are prone to formation of isomeric products. [29]…”

“…Fortunately, we discovered that catalytic Pd/C in the presence of a 5 % H 2 /N 2 mixture in DMA solvent effected aromatization, and the target bioactive honokiol analogue 17 was isolated in 27 % yield [28] . In contrast to the literature route, this strategy utilizes a complementary non‐aromatic core which may provide advantageous opportunities for diversification and avoids transformations such as electrophilic aromatic substitution that are prone to formation of isomeric products [29] …”

Total Synthesis of Lucidumone: Attempted Shortcuts, Dead Ends and Lessons Learnt

“…Inspired by Mohr’s recent use of Mitsunobu conditions for the O -alkylation of a diketone in the course of the total synthesis of aspergillusene B, we explored this type of reaction. 16 Gratifyingly, treatment of indanedione 26 and bridged lactone 41 with triphenylphosphine and diethyl azodicarboxylate (DEAD) led to the formation of the desired product 46 in 44% yield (Table 7 ). Using the benzyl-protected fragment 16 , a quick optimization allowed identification of DIAD as the optimal azodicarboxylate and PPh 3 as the optimal phosphine.…”