A practical way to synthesize chiral fluoro-containing polyhydro-2H-chromenes from monoterpenoids

Abstract

SummaryConditions enabling the single-step preparative synthesis of chiral 4-fluoropolyhydro-2H-chromenes in good yields through a reaction between monoterpenoid alcohols with para-menthane skeleton and aldehydes were developed for the first time. The BF3·Et2O/H2O system is used both as a catalyst and as a fluorine source. The reaction can involve aliphatic aldehydes as well as aromatic aldehydes containing various acceptor and donor substituents. 4-Hydroxyhexahydro-2H-chromenes were demonstrated to be capable of converting to 4-fluorohexahydro-2H-chromenes under the developed conditions, the reaction occurs with inversion of configuration.

N-Heterocyclic borneol derivatives as inhibitors of Marburg virus glycoprotein-mediated VSIV pseudotype entry

“… 16 Here, we screened over 170 natural derivatives in a Marburg glycoprotein-mediated VSIV pseudotype system. The library of natural compounds includes the derivatives of (+)-camphor, 17 , 18 (–)-borneol, 19 , 20 dehydroabietylamine, 21 , 22 para -mentha-1,8-dien-5,6-diol, 23 – 26 (–)-isopulegol, 27 deoxycholic acid, 28 (+)-usninic acid, 29 aminoadamantane 30 , 31 and azaadamantane 32 which were previously described by our colleagues. Among the tested derivatives, the bornyl ester containing saturated N-heterocycles exhibited the highest antiviral activity with several hit compounds identified.…”

Enantiomeric Isopulegol as the Chiral Pool in the Total Synthesis of Bioactive Agents

“…In this single-step preparative synthesis, using BF 3 • Et 2 O/H 2 O both as a catalyst and as a fluorine source, chiral 4-fluoropolyhydro-2H-chromenes 10 were prepared in good yields through a reaction between (À )isopulegol 2 and 3,4,5-trimethoxybenzaldehyde (Scheme 6). [67] Subsequently, the research group of Salakhutdinov synthesised fluoro-and hydroxy-containing octahydro-2H-chromenes by the Prins reaction starting from (À )-isopulegol 2 with carbonyl compounds of various types (aromatic, aliphatic, heteroaromatic aldehydes and aliphatic ketones) in the presence of the BF 3 • Et 2 O/H 2 O system in 2020 (Scheme 7). [68,69] The activity of the produced compounds against the influenza A/Puerto Rico/8/34 (H1 N1) virus was studied.…”

New trifluoromethylated sesquiterpenoids: synthesis, rearrangement, and biological activity

“…Research in this direction is relevant and interesting, since fluorinated analogs of natural compounds have been proven to be promising physiologically active substances. 19,[33][34][35][36][37][38][39] As part of our longstanding interest in natural compounds and their modification, we report the possibility of using tandem trifluoromethylation and isomerization reactions as an effective tool for the synthesis of fluorinated terpenoids. known biological activity and low toxicity, and can be used as a scaffold for the synthesis of physiologically active substances.…”

“…Research in this direction is relevant and interesting, since fluorinated analogs of natural compounds have been proven to be promising physiologically active substances. 19,33–39…”