Total Synthesis of Diverse Carbogenic Complexity within the Resveratrol Class from a Common Building Block

Abstract

Although biomimetic approaches have proven capable of converting resveratrol (1) concurrently into many of the more complex oligomers produced by plants throughout the world (such as 2-10), methods to access single members of the family have proven far more difficult to identify. Herein is described a strategy-level solution based on the use of a common building block, one distinct from Nature's starting material, that can participate in a variety of highly selective, reagent-controlled reaction cascades. These endeavors have led to the controlled synthesis of 25 natural products and analogues, molecules whose architectures encompass nearly all the carbogenic diversity of the resveratrol family.

Resveratrol-based benzoselenophenes with an enhanced antioxidant and chain breaking capacity

“…The efficient ring closure of the selenophene ring implies that 'in situ' generated SeCl 2 reacts almost exclusively with the C-2 nucleophilic carbon of the resorcin moiety of resveratrol and, hence, that the reactivity at C2 is much higher than at C4. Due to the presence of Cl 2 in the reaction mixture (eqn (2) 4 led to some 3 (10-15% yield) supporting the superior synthetic value of the adopted procedure. Whenever chlorination occurred, only one regioisomer of the monochloro derivative was observed under all the reaction conditions examined.…”

“…2 Currently, it is on the market as a food supplement because of its manifold positive activities on human health 3 and has been extensively investigated as a versatile platform for the design of natural product-like compounds. 4 Some of the biological effects of resveratrol are related to its antioxidant activity, as it prevents the oxidation of LDL in vitro and reduces the markers of oxidative stress in vivo. 5 The antioxidant activity depends on the 4′-OH group, which exhibits a superior H-atom transfer and peroxyl radical scavenging capacity compared to the resorcinol-type OH groups, due to the olefinic double bond contribution to resonance stabilization of the phenoxyl radical.…”

A flow-microreactor approach to protecting-group-free synthesis using organolithium compounds

“…The iodine-lithium exchange reaction of 35 followed by reaction with 3,5-dimethoxybenzaldehyde was conducted using a flow-microreactor system consisting of the integrated device (residence time in R2: 0.003 s) to produce 36 (ref. 49) in 81% isolated yield. Presumably, dehydration took place upon acidic work-up.…”

“…Application to formal synthesis of Pauciflorol F. Using the present method, Pauciflorol F 48 , a natural product isolated from stem bark, which has recently been synthesized by Snyder's group 49,50 and Sarpong's group 51 , was synthesized. The starting material 35 was prepared from commercially available 3,5-dimethoxyphenylmagnesium chloride in two steps (67% yield; Fig.…”

“…Presumably, dehydration took place upon acidic work-up. Treatment of 36 with HCl/i-PrOH in the presence of O 2 in a batch reactor gave 37 in 75% yield, which can be converted to Pauciflorol F by one-pot hydrogenation and epimerization (87%) 51 followed by deprotection (86%) 49,50 .…”