The story of alkannin and shikonin can be traced back many centuries. Extracts from the roots of Alkanna Tinctoria in Europe and Lithospermum Erythrorizon in the Orient, have been used as natural red dyes and as crude drugs that accelerated wound healing. Their first reported use can be found in the works of the Greek botanist and scholar Theophrastus (ca. 300 BC) and around 77 AD, Dioscorides who is considered the founder of pharmacology, described the properties of these red pigments in more detail in his De Materia Medica. In later years, shikonin has been applied to traditional Chinese medicine from the great surgeon Hua To (born ca. 136-141 AD). Nowadays alkannin is mainly used for food coloring and cosmetics but there is an extensive scientific research concerning both natural products in order to clarify their biological properties.

Alkannin and Shikonin and their derivatives are naturally occurring dyes found in the outer surface of the roots of many traditional medicinal plants of the Boraginaceae family (mainly in the genus Alkanna, Lithospermum, Arnebia and Echium). They show a broad spectrum of significant biological activities including anti-inflammatory, antibacterial, antifungal, immunostimulating, anticancer, analgesic, antipyretic as well as strong inhibition of the enzyme Topoisomerase I. The most prominent and unique feature is their wound healing properties, known from the ancient times. Recent in vivo studies showed that shikonin inhibits TNF-a-induced angiogenesis and B16 melanoma-induced angiogenesis in mice. It is noteworthy that angiogenesis (the growth of new blood vessels) plays an important role in the processes of development, wound repair and inflammation. It also contributes to various pathological conditions such as diabetic retinopathy, rheumatoid arthritis and cancer. In addition, various shikonin analogues inhibit the cell growth of various cancer cell lines, induce apoptosis in leukemia HL-60 cells and regulate the IGFs and VEGF in human prostate cancer cell lines.

The synthesis begins with the condensation of a well known synthon with a Michael acceptor (acrylonitrile or methyl acrylate) followed by protection of the resulting phenol which after reduction-oxidation afforded the corresponding formyl derivative. This key intermediate was subsequently subjected to an asymmetric allylboration with (+)-allyldiisopinocamphenyl borane prepared according to Brown's procedure. Having established the chiral center of the target molecule, we proceed to the completion of the side chain construction by protecting the hydroxyl group as a silyl ether, cleavage of the terminal double bond to the corresponding aldehyde and Wittig type elongation using the ylide of 2-iodopropane to afford the fully protected natural product. (R)-(+)-Shikonin was afforded after the final deprotections in high overall yield. The same route was followed using the other antipode of allyldiisopinocamphenyl borane reagent, leading to the formation of (S)-(-)-Alkannin.