Total Synthesis of Naturally Occurring 5,7,8-Trioxygenated Homoisoflavonoids

Abstract

Homoisoflavonoids are in the subclass of the larger family of flavonoids but have one more alkyl carbon than flavonoids. Among them, 5,7,8-trioxygenated homoisoflavonoids have not been extensively studied for synthesis and biological evaluation. Our current objective is to synthesize 2 5,7,8-trioxygenated chroman-4-ones and 12 5,7,8-trioxygenated homoisoflavonoids that have been isolated from the plants Bellevalia eigii, Drimiopsis maculata, Ledebouria graminifolia, Eucomis autumnalis, Eucomis punctata, Eucomis pallidiflora, Chionodoxa luciliae, Muscari comosum, and Dracaena cochinchinensis. For this purpose, 1,3,4,5-tetramethoxybenzene and 4′-benzyloxy-2′,3′-dimethoxy-6′-hydroxyacetophenone were used as starting materials. Asymmetric transfer hydrogenation using Noyori’s Ru catalyst provided 5,7,8-trioxygenated-3-benzylchroman-4-ones with R-configuration in high yield and enantiomeric excess. By selective deprotection of homoisoflavonoids using BCl3, the total synthesis of natural products including 10 first syntheses and three asymmetric syntheses has been completed, and three isomers of the reported dracaeconolide B could be provided. Our research on 5,7,8-trioxygenated homoisoflavonoids would be useful for the synthesis of related natural products and pharmacological applications.

Asymmetric hydrogenation and transfer hydrogenation in the enantioselective synthesis of flavonoids

“…In the following year, Seo and co-workers 93 reported the enantioselective synthesis of three natural 5,7,8-trioxygenated homoisoflavanones ( R )- 182–184 using the same synthetic strategy previously reported (Scheme 42). The racemic substrates ( rac )- 176–178 were treated with 30 mol% of ( R , R )- CAT5 and HCO 2 H/DBU as the hydrogen source in acetonitrile at 50 °C for 24 h resulting selectively in the corresponding ( R , R )- 179–181 cis -alcohols with excellent yields (94–97%) and enantioselectivities (92–99%).…”

“…The enantioselective synthesis of cis -3-benzylchroman-4-ols through a Ru-catalysed ATH–DKR allowed Seo's group 89,93 to synthesize natural and synthetic homoisoflavanones besides establishing a relationship between their antiproliferative activity potency and the absolute configuration. Most recently, two other groups reported almost simultaneously more direct approaches toward the cis -3-benzyl-chroman-4-ols through the one-pot CC/CO bond reduction catalysed by Rh III (ref.…”

A Comprehensive Review on Chemotaxonomic and Phytochemical Aspects of Homoisoflavonoids, as Rare Flavonoid Derivatives

“…Homoisoflavonoids (HIFs), a small, rare, and unique class of the flavonoids, are naturally occurring oxygen heterocyclic compounds possessing two aromatic rings, and an additional carbon between the B and C rings on the isoflavonoid skeleton ( Figure 1 ) [ 1 , 2 ]. As demonstrated in Figure 1 , the most updated classification of HIFs is categorized into five groups: sappanin, scillascillin, brazilin, caesalpin, and protosappanin types [ 3 , 4 ].…”

Rhodium-Catalyzed Asymmetric Transfer Hydrogenation/Dynamic Kinetic Resolution of 3-Benzylidene-Chromanones

“…The authors used the same strategy for the total synthesis of several 5,7,8-trioxygenated chroman-4-ones and homoisoflavonoids …”