Total Syntheses of Plagiochins A and D, Macrocyclic Bis(bibenzyls), by Pd(0) Catalyzed Intramolecular Stille-Kelly Reaction1

Total Synthesis of Plagiochin D by an Intramolecular SNAr Reaction

“…The spectroscopic data for compound 4 are identical to those of plagiochin D reported in the literature. [4,11,23] Thus, the bis(bibenzyl) system has been prepared by biaryl ether formation (S N Ar) in a critical key 16-membered ring-closing step in 50 % overall yield starting from four simple and readily available aromatic subunits (fragments A-D). This compares with the previously described Wurtz-type cyclization of an ethylene bridge (Nógrádi and coworkers, 7.4 %), [11] the Still-Kelly reaction to form the biaryl (Fukuyama and co-workers, 8.6 and 9.0 %), [12,13] and the McMurry protocol to form a stilbene bridge (Speicher and co-workers, 11.9 %), [14] all of which start from elaborated precursors.…”

Organotin Reagents in Cross‐Coupling Reactions

“…In a recent publication [49], Toshima et al reported the use of (MeCN) 2 PdCl 2 in an intramolecular vinyl-vinyl coupling to provide a 20-membered ring precursor to the macrolide antibiotic apoptolidin; LiCl and Ph 2 PO 2 NBu 4 were used as additives. Finally, a mention must be made of a strategy [92] for an intramolecular aryl-aryl coupling leading to plagiochin A and D: the precursors for both macrocyclic bis(bibenzyls) bear terminal bromoarene moieties, which can undergo reaction with hexamethylditin and (Ph 3 P) 4 Pd. This reaction leads to intermediates, in which one of the Br atoms has been replaced by a SnMe 3 moiety, and further heating gives the coupling product (Scheme 6.30).…”

Anti-MRSA activity of isoplagiochin-type macrocyclic bis(bibenzyl)s is mediated through cell membrane damage

“…[1][2][3][4] These compounds have characteristic structures, and exhibit diverse biological activities, [5][6][7][8][9][10][11][12] and so there is great interest in the synthesis of these compounds and their analogs. [13][14][15][16][17][18][19][20] We recently reported that riccardin-class macrocyclic bis-(bibenzyl)-type phenolic compounds, such as riccardin C (1), exhibit potent antibacterial activity towards methicillin-resistant Staphylococcus aureus (anti-MRSA activity), comparable to that of clinically used drugs, such as vancomycin and linezolid. 21,22 In order to understand the structure-activity relationship of riccardin-C class bis(bibenzyl)s, we previously prepared several riccardin C derivatives, and found that the number and position of hydroxyl group(s) on the benzene ring are important for anti-MRSA activity.…”