Enantioselective Total Synthesis of the Lignan (+)‐Linoxepin

Abstract

An enantioselective total synthesis of the natural (+)-linoxepin (1) was accomplished in eleven steps from bromovanin (24). Key steps are a domino carbopalladation/ Mizoroki-Heck reaction with the formation of a pentacyclic system, an asymmetric hydroboration as well as an oxidative lactonization.

Origin of Stereocontrol in Guanidine-Bisurea Bifunctional Organocatalyst That Promotes α-Hydroxylation of Tetralone-Derived β-Ketoesters: Asymmetric Synthesis of β- and γ-Substituted Tetralone Derivatives via Organocatalytic Oxidative Kinetic Resolution

“…The newly developed oxidative kinetic resolution method for tetralones was applied to the synthesis of (+)-linoxepin ( 13 ), which was isolated from Linum perenne as a caffeic acid dimer possessing an oxidation-prone dihydronaphthalene structure with a tetrasubstituted double bond embedded in a highly strained dihydrooxepine ring system (Scheme ). , …”

Recent strategies and tactics for the enantioselective total syntheses of cyclolignan natural products

“…98) and subsequently reported a related enantioselective synthesis of (+)-linoxepin ( 106 ) in 2014. 99 The Tietze group, like the Lautens lab, chose to tether the aryl rings by constructing the C3–C2′ linkage at the beginning of their synthesis, but the key disconnection in this case is between the C2–C7′ bond (Scheme 50). This strategy most closely aligns with pathway D from Fig.…”

Diastereoselective Formal [5+2] Cycloaddition of Diazo Arylidene Succinimides-Derived Rhodium Carbenes and Aldehydes: A Route to 2-Benzoxepines

“…These are only a few illustrative examples, in addition to compounds with hypotensive, antianaphylactic, and antitumor activity. In addition, the 2-benzoxepine core is found in many natural products, namely, Dioscorealide B, a pharmacologically active naphthofuranoxepin isolated from rhizome of Dioscorea membranacea ; Linoxepin, a lignan-containing benzonaphtho­[1,8- bc ]­oxepine moiety isolated from Linum perenne L. (Linaceae); Alterlactone, a mycotoxin produced by Alternaria sp . ; fungal metabolites Arugosins; Cladoacetals A and B isolated from solid-substrate fermentation cultures of fungicolous isolate (NRRL 29097); and Xylarinol A and 8-Chloroxylarinol A isolated from the fruiting bodies of the Xylaria polymorpha and from the extract of the grain-based culture of Malbranchea flavorosea , respectively (Figure ).…”