Scientists are currently exploring ways to develop novel pharmaceuticals by synthesizing the bioactive compounds found in Chinese herbal medicines. By combining traditional knowledge with modern scientific methods, this collaborative effort focuses on the pharmacologically relevant compounds found in medicinal plants for large-scale synthesis. An important compound in this context is marylinin, a type Illicium sesquiterpene that was isolated from the fruit in 2002. Illicium Merrillian. This plant Star anise belongs to the same genus as fennel. Illicium sesquiterpenes There are naturally occurring compounds that hold promise for treating diseases of the nervous system. However, marylanin has a complex structure with a central arrangement of six consecutive stereogenic carbon centers, three quaternary carbon stereogenic centers, and three rings joined by two carbons. This complexity has created challenges for the synthetic synthesis of marylanin, which has led to limited progress in its practical application since its isolation.

In a breakthrough study published in the journal Organic lettersA research group led by Tokyo University of Science (TUS) Assistant Professor Takatsugu Murata and Professor Isamu Shina has succeeded in synthesizing marylinin, opening the door to its synthetic synthesis nearly 20 years after the compound was isolated.

“Illicium sesquiterpenes are a group of compounds expected to be effective against neurological diseases, but their highly oxidized and ring-fused structures make them difficult to synthesize synthetically. However, we have synthetic techniques and The synthesis of highly complex compounds such as taxol is known. Dr. Murta says. “Therefore, we wanted to synthesize the world’s first synthetic merilinin, which is expected to have anti-arthritic activity, and create a lead compound that could help treat neurological diseases.”

By Wicker-type oxidation of dilatonin, marylanin can be obtained with yields as high as 80%. However, the challenge lies in efficiently preparing precursor compounds for dilatone. To address this, the researchers used a total of 30 reaction steps, covering the synthesis of precursors to the final production of merillanin. The process begins with a Makayama aldol reaction, involving an enol silyl ether and acetaldehyde. This reaction leads to the creation of a dithioacetal, a compound containing a quaternary carbon stereogenic center. Next, the dithioacetal undergoes a series of reactions with an iodo compound, resulting in the formation of an α,β-unsaturated ester with an aldol structure. The next steps involved a reductive intramolecular cyclization of this compound to cyclopentene, followed by an intramolecular Michael reaction with a total yield of 1.6% to form the tricyclic dilactone. Tricyclic dilactone is an important intermediate for the commercial production of a wide variety of dilactones. Illicium sesquiterpene compounds, including marylanin.

The researchers pointed out that if marylanin had more bioactivity, the amount needed for treatment would be much lower. (According to the isolation report, 3 mg of merillanin was isolated from 30 kg of fruit.) Interestingly, it will be possible to evaluate its bioactivity using the synthetic version developed by the group.

The synthesis method also revealed the absolute configuration of marylinin, which until now was known only as relative configurations. The proposed synthesis method for merilinin represents another milestone for the research group, which had previously succeeded in synthesizing naturally occurring tanzavic acid B found in fungi. Lemon pencil which has the ability to produce antibiotics against multi-drug resistant bacteria.

The research group’s continued dedication to the synthesis of compounds with interesting biological activities holds promise for future discoveries in the field of drug development. Types of Illicium The genus has long been used as a medicinal herb to treat conditions such as rheumatoid arthritis and traumatic wounds, and the synthesis of marylinin may also contribute to advances in these areas. “The proposed synthesis method for merilinin will help to develop suitable drugs for the treatment of nervous system diseases such as arthritis and neuropathic pain, improving the prognosis of neurological diseases and improving the patient’s quality of life,” “ Professor Sheena concludes.

Source: Tokyo University of Science