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

Abstract

Mulberry Diels-Alder-type adducts (MDAAs) are unique phenolic natural products biosynthetically derived from the intermolecular [4 + 2]-cycloaddition of dienophiles (mainly chalcones) and dehydroprenylphenol dienes, which are exclusively distributed in moraceous plants. A total of 166 MDAAs with diverse skeletons have been isolated and identified since 1980. Structurally, the classic MDAAs characterized by the chalcone-skeleton dienophiles can be divided into eight groups (Types A - H), while others with non-chalcone dienophiles or some variations of classic MDAAs are non-classic MDAAs (Type I). These compounds have attracted significant attention of natural products and synthetic chemists due to their complex architectures, remarkable biological activities, and synthetic challenges. The present review provides a comprehensive summary of the structural properties, bioactivities, and syntheses of MDAAs. Cited references were collected between 1980 and 2021 from the SciFinder, Web of Science, and China National Knowledge Internet (CNKI).

Keywords: Bioactivity; MDAAs; Mulberry Diels–Alder-type adducts; Natural products; Synthesis.

Scheme 1

The biosynthesis pathway of classic MDAAs

Fig. 1

Structures of eight important groups of classic MDAAs (Types A − H)

Fig. 2

Structures of dehydroprenyl-2-arylbenzofuran type MDAAs (Type A)

Fig. 3

Structures of dehydroprenyl-2-arylbenzofuran type MDAAs (Type A, continued)

Fig. 4

Structures of dehydroprenyl-2-arylbenzofuran type MDAAs (Type A, continued)

Fig. 5

Structures of dehydroprenylstilbene type MDAAs (Type B)

Fig. 6

Structures of dehydroprenylchalcone type MDAAs (Type C)

Fig. 7

Structures of dehydroprenylflavone type MDAAs (Type D)

Fig. 8

Structures of dehydroprenyldihydroflavone type MDAAs (Type E)

Fig. 9

Structures of dehydroprenylsanggenonflavone type MDAAs (Type F)

Fig. 10

Structures of dehydroprenylcoumarin type MDAAs (Type G) and simple or other dehydroprenylphenol type MDAAs (Type H)

Fig. 11

Structures of non-classic MDAAs (Type I)

Scheme 2

Syntheses of mulberrofuran J hexamethyl ether (1a), mongolicin F hexamethyl ether (2a), chalcomoracin heptamethyl ether (5a), and mulberrofuran C heptamethyl ether (6a) by the Rizzacasa group

Scheme 3

Syntheses of dienes S28 and S31 by the Lei group

Scheme 4

Syntheses of kuwanons X and Y (58 and 61) and kuwanol A (64) by the Lei group

Scheme 5

Syntheses of ( ±)-kuwanol E (62) and ( ±)-kuwanon Y heptamethyl ether (61a) by Iovine and coworkers

Scheme 6

Syntheses of ( ±)-dorsterone pentamethyl ether (79a) and ( ±)-kuwanon V pentamethyl ether (87a) by the Rahman group

Scheme 7

Syntheses of ( ±)-kuwanon I heptamethyl ether (78a) and ( ±)-kuwanon J heptamethyl ether (81a) by the Rizzacasa group

Scheme 8

Asymmetric total syntheses of ( +)-brosimones A and B (80 and 77) by the Porco group

Scheme 9

Syntheses of dienophiles (S79, S81, and S82) and dienes (S81 and S85) by the Lei group

Scheme 10

Enantioselective total syntheses of brosimone B (77), kuwanon I (78), and kuwanon J (81) by the Lei group

Scheme 11

Enantioselective total synthesis of brosimone A (80) by the Lei group

Scheme 12

Syntheses of kuwanons G and H (92 and 93) by the Tang group

Scheme 13

Asymmetric total syntheses of sanggenons C and O (130 and 131) by the Porco group

Scheme 14

Synthesis of palodesangrens B and D methyl ethers (139a and 141a) by the Ploypradith group

Scheme 15

Synthesis of ( ±)-sorocenol B (149) by the Porco group

Scheme 16

Synthesis of ( ±)-morusalbanol A pentamethyl ether (148a) by the Chee group

Scheme 17

Syntheses of dienophiles (S166 and 168) by the Lei group

Scheme 18

Syntheses of dienes (S176, S182, and S186− S188) by the Lei group

Scheme 19

MaDA-mediated chemoenzymatic total syntheses of chalcomoracin (5), 18″-O-methychalcomoracin (5b), guangsangon E (56), kuwanol E (62), kuwanon J (81), and deoxyartonin I (102) by the Lei group

Scheme 20

MaDA-mediated chemoenzymatic total syntheses of artonin I (101) and dideoxyartonin I (101a) by the Lei group