Enantioselective Synthesis of C(8)-Hydroxylated Lignans—Early Approaches and Recent Advances

Abstract

α-Hydroxylated lignans, dimers of phenylpropene with important biological properties, have been enantioselectively prepared following different synthetic strategies. The early approaches to optically active α-hydroxylated lignans involved the use of chiral auxiliaries or were based on the stereoselective α-oxygenation of lactone lignan enolates. Most recently compounds from the pool of chiral building blocks, such as sugars or malic acid, became important starting materials for the asymmetric construction of α-hydroxylated lignans. The biaryl lignans schizandrin and isoschizandrin were obtained either by oxazoline-based biaryl coupling as key reaction or by asymmetric hydrogenation followed by stereoselective water addition. The preparation of furofuran lignans was achieved from dialkyl malates and tetrahydrofuran lignans were accessed from arabinose and xylose, respectively. Arabinose and malic acid, as well as unfunctionalized lactone lignans, prepared from chiral β-benzyl-γ-butyrolactones, were employed for the synthesis of α-hydroxylated lactone lignans. Further details of the strategies and an outlook for future investigations into methodology and interesting targets are provided in this review.Open image in new window