3). This one-pot macrocyclization goes through oligomeric intermediates that increase in length of For the highest yield of the macrocyclization, it is best to use purified monomer 6, as is done on the large-scale pathway. In the case of the small scale, each step was continued without purification using column chromatography, and monomer 6 was therefore part of a mixture with other aldehyde-containing impurities (Figure ). These impurities undergo condensation with the benzylic nitriles under the reaction conditions to form unwanted side products, thereby lowering yields. In the presence of any unwanted side products on either the large or small scales, the cyanostar can be readily purified using column chromatography or flash chromatography with conditions optimized for high cyanostar recovery. More information on the purification of cyanostar can be found in the Supplementary Information. Overall, two reliable and relatively easy synthetic pathways toward cyanostar have been developed (Table ). The large-scale pathway yields 12 grams of cyanostar in a 50% overall yield over 6 steps. The most notable hurdle in this pathway is the quantity of hazardous reagents required, such as LiAlH4 and KCN. LiAlH4 is pyrophoric and corrosive. If it comes into contact with water, flammable hydrogen gas will form and may ignite spontaneously. KCN is poisonous, and the median lethal dose through skin exposure is 100 mg / kg. This threshold is crossed in the case of the large-scale pathway. However, we mitigate the exposure to large quantities of hazardous materials in the small-scale synthesis, which requires nearly an order of magnitude less hazardous material at each of these steps. The benefit of the large-scale pathway is that it is optimized to obtain pure intermediates at each step, which reduces byproduct interferences in subsequent reactions. This pathway would be best to follow in the case of needing extra pure intermediates and large amounts of cyanostar.