Enantioselective Route to Threo 8.0.4'-Type Neolignans: Synthesis of (-)-Virolin

Abstract

A combination of diastereoselective borohydride reduction of the substituted -bromo-propiophenone [(±)-2] and microbial-assisted hydrolysis of its corresponding bromohydrin acetate using Rbizopus nigricans, led to the chiral epoxide, (-)-6. The regiospecific opening of this epoxide, produced pure (-)-virolin [1], whose absolute configuration could be assigned through this sequence as 75,85. It is possible, by selecting the appropriate starting materials, to obtain different chiral three neolignans of the 8.0.4'-type and to predict their configuration.Virolin, a neolignan of the 8.0.4'-type, corresponding to the threo series, has been isolated from the leaves of Virola surinamensis (Myristicaceae) (1). We have performed its racemic synthesis ( 2), but neither its enantioselective synthesis nor its absolute configuration has been previously reported. Continuing with our project aimed at the enantioselective synthesis of 8.0.4'-type neolignans, we wish to report herein our efforts towards the asymmetric synthesis of threo virolin [(-)-!], involving a procedure for preparing chiral threo alcohols of predictable stereochemistry. We followed the nomenclature for neolignans proposed by Gottlieb (3).

Determination of absolute configuration of secondary alcohols using lipase‐catalyzed kinetic resolutions

“…They assigned the absolute configuration of the fast-reacting enantiomer as (1S,2S) by both 1 H NMR of amethoxy-a-(trifluoromethyl)phenylacetate (MTPA) derivative and the empirical rule, Scheme 5. 50 This case required a combination of methods because the enantioselectivity of the hydrolysis was too low to make a reliable assignment on the empirical rule alone. Scheme 4.…”

A new lignan from Schefflera arboricola

“…Moreover, their optical rotations are different ( 1 , [ α ] D 25 33.3; 4-[3′-(hydroxymethyl)oxiran-2′-yl]-2,6-dimethoxyphenol, [ α ] D 26 −3.0), which suggest 1 has a 7′ S ,8′ S configuration. 19–23 Therefore, the structure of 1 is assigned as a new lignan linked via a C-9−C-9′ ether, which is named as arborlignan A.…”

The Stereoselective Synthesis of Neolignans

“…Regioselective epoxide opening at C(8) was achieved with deprotonated isoeugenol in refluxing dioxane providing (-)-virolin (177) in 87% yield and 78% ee (Scheme 47). 142…”