Morusalones A–D, Diels–Alder Adducts with 6/7/6/6/6/6 Hexacyclic Ring Systems as Potential PTP1B Inhibitors from Cell Cultures of Morus alba

Abstract

Morusalones A−D (1−4), a new class of Diels−Alder adducts featuring unprecedented 6/7/6/6/6/6 hexacyclic core skeletons with a unique bridged cycloheptenone ring, were isolated from Morus alba cell cultures. The biosyntheses for 1−4 were proposed through an unusual Diels−Alder cycloaddition with quinostilbenes as dienophiles and prenyl 2-phenylbenzofuran as a diene to yield the typical methylhexene unit and a rare intramolecular nucleophilic addition to form the cycloheptenone ring. Compounds 1−4 exhibited protein tyrosine phosphatase 1B inhibitory activity.

Rearranged Diels–Alder Adducts and Prenylated Flavonoids as Potential PTP1B Inhibitors from Morus nigra

“…The root bark of some Morus species has been used as a traditional Chinese medicine ( Mori Cortex Radicis , Sang-Bai-Pi in Chinese) to treat diabetes, arthritis, hypertension, fever, and hypoglycemia . Previous phytochemical investigations on this genus have led to reports on a series of structurally diverse phenolic compounds, such as flavonoids, stilbenes, 2-arylbenzofurans, coumarins, and Diels–Alder adducts, most of them prenylated. , Diels–Alder adducts containing methylcyclohexene moieties are considered to be the characteristic constituents in Morus species and are biosynthetically derived from the intermolecular [4 + 2] cycloaddition of chalcones (dienophiles) and prenylated phenols (dienes). To date, more than 100 various Diels–Alder adducts have been reported from Morus .…”

“…To date, more than 100 various Diels–Alder adducts have been reported from Morus . Morus Diels–Alder adducts can be classified as six types of skeletons, e.g., chalcone–stilbene, chalcone–2-arylbenzofuran, chalcone–chalcone, chalcone–benzaldehyde, chalcone–flavone/dihydroflavone, and other types of adducts. , More importantly, numerous Diels–Alder adducts have been reported to feature bioactivities such as anticancer, , antispasmodic, antioxidant, , anti-inflammatory, , anti-Alzheimer’s disease, antimicrobial, antivirus, and outstanding PTP1B inhibitory effects, , leading to a growing interest in their biological activities and total synthesis. , …”

“…Morus Diels− Alder adducts can be classified as six types of skeletons, e.g., chalcone−stilbene, chalcone−2-arylbenzofuran, chalcone− chalcone, chalcone−benzaldehyde, chalcone−flavone/dihydroflavone, and other types of adducts. 4,5 More importantly, numerous Diels−Alder adducts have been reported to feature bioactivities such as anticancer, 6,7 antispasmodic, 8 antioxidant, 9,10 anti-inflammatory, 10,11 anti-Alzheimer's disease, 12 antimicrobial, 13 antivirus, 14 and outstanding PTP1B inhibitory effects, 4,15 leading to a growing interest in their biological activities and total synthesis. 16,17 Type 2 diabetes (T2D) is a multifactorial endocrine disease accounting for approximately 90% of the 463 million people with diabetes worldwide in 2019.…”

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

“…+ 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)…”

Enzymatic intermolecular Diels-Alder reactions in synthesis: From nature to design

“…Moraceous plants are rich sources for isolating a new family of D-A type natural products, containing more than 100 different members with diverse biological activities, including anti-diabetic [65,66] and anti-microbial activities [67]. These molecules originate from enzymatic intermolecular Diels-Alder reactions of a chalcone dienophile moiety and four different dehydroprenyl diene moieties [i.e., flavonoids, chalcones, stilbenes, and 2-aryl-benzofuran] [68] as shown in Fig.…”