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

Abstract

This review highlights strategies for the enantioselective total synthesis of cyclolignan natural products from 2000 to 2021. Each subsection focuses on the key strategic disconnections and the enantioselective steps controlling asymmetric induction.

Tandem Hock and Friedel-Crafts reactions allowing an expedient synthesis of a cyclolignan-type scaffold

“…This structure was unambiguously confirmed by X-ray crystallographic analysis (Figure 1). Interestingly, the 1-aryltetraline product 6 holds a skeleton similar as that of cyclolignan natural products (Figure 2), which have often been targeted by total synthesis [18]. Some of them like podophyllotoxin [25] and semisynthetic derivative etoposide [26] have demonstrated valuable anticancer properties [19,20].…”

“…Overall, a three-reaction process will thus be performed in one pot (Scheme 1c), successively involving a Schenck-ene photooxygenation of the alkene (A), an acid-catalyzed Hock cleavage of hydroperoxide B generating an aldehyde derivative (C), and an acid-catalyzed Friedel-Crafts reaction in presence of an aromatic nucleophile leading to D [17]. In principle, a second Friedel-Crafts reaction is possible upon elimination of the resulting benzylic alcohol on D, allowing another arylation forming E [18]. This complex sequence of transformations is herein applied to the synthesis of 1-aryltetralines, analogues of cyclolignan natural products having important medicinal applications [19,20].…”

Cyclolignan Synthesis Streamlined by Enantioselective Hydrogenation of Tetrasubstituted Olefins

“…Tackling these issues will require that inherently exhaustible classical semisynthetic derivatization approaches to cyclolignans, which rely heavily on natural sources and are handicapped by the in exible structural features of such sources, be supplemented with more powerful, diversity-oriented de novo strategies. 24,25 In 2014, Thomson and coworkers reported diversity-oriented synthesis (DOS) of six cyclolignans by means of novel tandem stereoselective oxidative [3,3]-sigmatropic rearrangement/Friedel-Crafts arylation reactions between electron-rich arenes and N-allylhydrazones (Fig. 1a), 26 and Maimone and Ting reported DOS of PPT and some 7'-aryl analogs via elegant Pd-catalyzed C(sp 3 )-H arylation reactions (Fig.…”

“…Cognizant of the fact that cyclolignans share a common feature: the aryl substituent at C-7′ is either synor antito the substituent at C-8′, [19][20][21][22][23][24][25] we conjectured that the asymmetric hydrogenation of 1,2dihydronaphthalene tetrasubstituted ole ns 1 as information-rich hidden retrons, 35 comprising the vital scaffold and functionalities of cyclolignans and have a deliberately installed ester group to serve as a handle for subsequent epimerization and other manipulations, might provide a universal platform for cyclolignan synthesis (Fig. 1f).…”

Asymmetric total synthesis of four bioactive lignans using donor–acceptor cyclopropanes and bioassay of (−)- and (+)-niranthin against hepatitis B and influenza viruses

“…Lignans are attracting considerable attention due to their widespread distribution in plants and their varied bioactivity. 1–5 For example, matairesinol, 2 dimethylmatairesinol, 3 yatein, 4 and niranthin 5 are found in nature and exhibit e.g. , cytotoxicity, 2 b , d ,3 b ,4 b anti-bacterial, 2 c anti-allergic, 3 c anti-viral, 4 d ,5 b , e anti-leishmanial, 5 d and strong insect-feeding-deterrent activity.…”