Morusalisins A-F, six new Diels-Alder type adducts, as potential PTP1B inhibitors from cell cultures of Morus alba

Mulberry Diels–Alder-type adducts: isolation, structure, bioactivity, and synthesis

“…2 and 3). In addition, there were only eight type A of MDAAs (50)(51)(52)(53)(54)(55)(56)(57) with the diene moiety on A ring (C-5) of 2-arylbenzofuran (Fig. 4).…”

“…+ 130.7 [137] M. alba [137] ( −)-Morusalone A (156) − 129.7 [137] M. alba [137] ( −)-Morusalone B (157) − 132.9 [137] M. alba [137] Morusalone C (158) + 113.3 [137] M. alba [137] Morusalone D (159) + 109.4 [137] M. alba [137] Morusalisin A (160) + 93.7 [51] M. mongolica [51] Mongolicin B (161)…”

“…The others were macrourin E (60) [19] in type B, multicaulisin (99) [114] in type D, sanggenon G (124) [121], sanggenon T (125) [123], and sanggenol M (126) [122] in type E. Morushalunin (4) [26] isolated in M. alba was one of the only three methylated natural MDAAs, and the others were morbilisin D (36) [39] of the same type A from M. notabilis and kuwanon J 2,4,10"-trimethyl ether (82) [100] of type C from M. alba. Compounds 5-23 represent a remarkable series of cis-trans type A-I MDAAs initially detected in plants of Morus [4,14,15,22,23,39,42,47,48,[51][52][53][54]. Chalcomoracin (5), which is the first example of MDAAs, was isolated from the diseased mulberry leaves (M. alba) by Takasugi et al in 1980 [4].…”

“…Due to their undefined absolute configurations of C-22", 14 and 15 were randomly assigned the R*-and S*-configurations, respectively, for the distinguishment of them. Morusalisin D ( 16) and its C-21" hydroxylated derive, morusalisin E (17), were recently obtained from cell cultures of M. alba, and the absolute configuraton of C-21" of 17 has not been confirmed [51]. The structures of compounds 18 − 22 [15,22,39,48] were characteristic of a 6-membered oxygen ring, which might be formed by the intramolecular nucleophilic addition of the steric vicinal hydroxyl (3′-or 5′-OH) with the olefin (C-1") of the original methylcyclohexene ring.…”

“…The orientations of 5-OH in 29 and the epoxy ring in 30 were not yet determined. Compounds 31 − 48, a kind of ketalized type A-I MDAAs, were almost only discovered from the species of Morus [23,25,29,39,40,46,50,51,54,64,[78][79][80]. All ketalized MDAAs were reported as cis-trans configuration based on the coupling constants of H-4" with H-3" and H-5" (small J 3"/4" and large J 4"/5" ).…”