Enantioselective Total Synthesis of (−)‐Spiroxins A, C, and D

Abstract

Spiroxins A, C, and D are metabolites that have been identified in the marine fungal strain LL‐37H248. Their unique polycyclic structures and intriguing biological activities make them attractive targets for the synthetic community. Based on a scalable enantioselective epoxidation of 5‐substituted naphthoquinone, an oxidation/spiroketalization cascade, ortho‐selective chlorination of the phenol unit, and oxime‐ester‐directed acetoxylation, an enantioselective total synthesis of (−)‐spiroxins A and C and the first total synthesis of (−)‐spiroxin D have been achieved.

Marine natural products

“…271 A homodimeric bispyrrolidinoindoline dioxopiperazine alkaloid isolated from sponge-derived Aspergillus violaceofuscus has been prepared, 272 and synthesis of chlorinated alkaloids gymnastatin G and dankastatins B and C has also been achieved. 273 Cyclohexenone derivative pleosporol A (and its stereoisomers) has been prepared from arabinose, 274 peniciaculins A and B and hydroxysydonic acid have been synthesised via an enantioselective method, 275 as have (+)-peniciketals A and B, 276,277 and (−)-spiroxin D. 278 In silico prediction of SARS-CoV-2 main protease binding ability for marine fungal compounds predicted wailupemycins H and I, and cottoquinazoline B to have high nanomolar inhibition for preventing viral replication, 279 and another in silico study indicated that epolactaene would also inhibit this protease. 280 3-Bromoascochlorin suppressed small cell lung cancer growth in a xenogra mouse model without affecting body weight.…”

Spirobisnaphthalenes from Fungi, Biological activities and Total Synthesis: A Research Review

“…In 2021, attracted by the promising biological activities and challenging polycyclic architecture, Hu and coworkers designed another route to synthesize (−)‐spiroxin C, followed by the late‐stage functional group transformation to afford (−)‐spiroxin A and D (Scheme 11). Notably, the commercially available juglone 11 ‐ 1 was the only starting material [52] . At the beginning, 11 ‐ 3 was prepared as a single product through the sequence hydroxy group protection by 4‐methylbenzyl, enantioselective epoxidation catalysed by cinchona, then regioselective and diastereoselective reduction using (CH 3 ) 4 NBH(OAc) 3 , and hydroxy group protection with TBS group.…”

“…Notably, the commercially available juglone 11-1 was the only starting material. [52] At the beginning, 11-3 was prepared as a single product through the sequence hydroxy group protection by 4-methylbenzyl, enantioselective epoxidation catalysed by cinchona, then regioselective and diastereoselective reduction using (CH 3 ) 4 NBH(OAc) 3 , and hydroxy group protection with TBS group. Moreover, the epoxide unit of 11-3 was identical to those of natural products identified with the X-ray crystallographic analysis.…”

Poly(arylene piperidine) Quaternary Ammonium Salts Promoting Stable Long‐Lived Room‐Temperature Phosphorescence in Aqueous Environment

“…These simple and effective approaches overcome the inherent disadvantages of RTP crystalline materials, such as harsh growth environments, challenging preparation processes, and inferior reproducibility. [ 27 ] Although polymeric RTP materials are superior to crystalline materials in terms of preparation, flexibility, and transparency, there are still certain limitations. The short lifetimes in polymeric RTP systems are primarily caused by the extremely rapid and severe nonradiative decay of triplet excitons.…”