Total Syntheses of (+)-Peniciketals A-B and (−)-Diocollettines A Exploiting a Photoisomerization/Cyclization Union Protocol

Abstract

A late-stage photoisomerization/cyclization union tactic, in conjunction with Type I Anion Relay Chemistry (ARC), permits enantioselective total syntheses and then biological evaluation of (+)-peniciketals A and B. The photochemical protocol was further showcased by an efficient three-step construction of the architecturally complex polycyclic skeleton found in (−)-diocollettines A. The mechanism and diastereoselectivity of the photochemical protocol have also been explored by both experiment and density functional theory calculations.

Antiproliferation- and Apoptosis-Inducible Effects of a Novel Nitrated [6,6,6]Tricycle Derivative (SK2) on Oral Cancer Cells

“…Although dioxabicyclo[3.3.1]nonane derivatives have frequently been synthesized, their anticancer effects have rarely been investigated. Recently, peniciketal A, a Penicillium raistrickii -derived spiroketal compound containing a benzo-fused 2,8-dioxabicyclo[3.3.1]nonane core, was discussed [ 29 , 30 ]. Peniciketal A had IC 50 values of 33.50, 56.85, and 60.64 μM for the 24 h treatment and 18.99, 45.14, and 39.94 μM for the 48 h treatment of leukemia cells (THP-1, K562, and HL60).…”

Antioral Cancer Effects by the Nitrated [6,6,6]Tricycles Compound (SK1) In Vitro

“…Compounds with the bicyclo[3.3.1] skeleton also belong to the nitro-group-containing drugs and may exhibit anticancer effects. For example, peniciketal B, a spiroketal containing a benzo-fused bicyclo[3.3.1] skeleton [ 36 ], showed an IC 50 value of 6.8 μM for A549 lung cancer cells but showed low cytotoxicity to normal lung fibroblast cells (IMR90) [ 37 ]. For comparison, the IC 50 value of SK1 at 24 h MTS assay for oral cancer cells (Ca9-22, CAL 27, and HSC-3) was 2.8, 4.4, and 4.4 μg/mL (7.93, 12.46, and 12.46 μM) without cytotoxic effects to non-malignant oral cells.…”

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.…”

“…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…”