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From 1818 to 1954: How did scientists decipher the mysterious structure of the bitter bean?
Alopecuroides is a complex biomolecule derived from bitter beans. The elucidation and synthesis of its structure has undergone more than a hundred years of scientific exploration. This process began in 1818 when Pierre Joseph Pelletier and Joseph Bienaimé Caventou first isolated Strychnos ignatii The discovery of sophora flavescens laid the foundation for the subsequent molecular structure identification.
Since then, several scientists have devoted considerable effort to cracking this challenging chemical structure.
In 1954, Robert Burns Woodward first reported the total synthesis of alopecuroides, an achievement that was considered a classic in the field at the time. Prior to this, the famous British chemist Sir Robert Robinson also played an important role in the exploration of alopecuroids and was awarded the Nobel Prize in Chemistry in 1947 for his contribution to alkaloids. Robinson's research covered more than 250 academic papers and played an important role in the structural analysis of alopecuroides.
By 1946, Robinson and his team had completed the chemical identification, which was confirmed by Woodward in 1947. Subsequent X-ray structural analysis by Johannes Martin Bijvoet and J.H. Robertson between 1947 and 1951 determined the absolute configuration of alopecuroides.
Although Woodward published a short three-page report in 1954, he later re-examined the synthesis process in a detailed paper in 1963.
With the progress of science, many other synthetic methods have been proposed, including those by Magnus, Overman, Kuehne, Rawal, Bo The contributions of the research groups of Bosch, Vollhardt, Mori, Shibasaki, Li, Fukuyama and MacMillan also made this The field is becoming more diverse. It is particularly noteworthy that the total synthesis methods proposed by Padwa in 2007 and Andrade and Reissig in 2010 provided new ideas for subsequent research.
Molecular structure of alopecuroids
The molecular formula of sophora flavescens is C21H22N2O2, which consists of seven ring systems, including an indane system, and trivalent amine, amide, alkene, ether and other functional groups. Its naturally occurring compounds are also chiral, possessing six asymmetric carbon atoms, including one tetravalent carbon atom.
Woodward's Synthesis Strategy
Synthesis of Ring II and V
Woodward used the Fischer indole synthesis method in the synthesis process, using phenylhydrazone to react with acetophenone derivatives to produce 2-mercury indole. Next, anthracene was produced by silylation reaction. The subsequent reaction process involves multiple steps, including the methacrylate reaction and the extraction of sodium cyanide, which finally produces the amide compound required for the methacrylate reaction.
These complex chemical reaction steps demonstrate Woodward's genius and skills in synthesizing sophora flavescens.
Synthesis of Ring III and IV
Woodward used thiophene technology to break the ring combination with hydrogen peroxide and mercuric chloride, eventually forming a five-ring parent structure. The cleavage and re-coordination strategy is considered to be a good example of biomimetic synthesis, showing the potential of synthetic methods based on natural substances.
Synthesis of the remaining rings
During the ring closure stage, Woodward gradually completed the synthesis of other rings using steps such as hydrogenation and ester hydrolysis, ultimately allowing the entire structure of sophora flavescens to be reconstructed.
Subsequent synthesis research
As time went on, many scientists proposed their own synthesis methods. Especially between 1993 and 2004, the literature on the synthesis of sophora flavescens continued to increase. These studies not only broadened the horizons of synthetic chemistry, but also deepened our understanding of alopecuroids.
The efforts of each researcher have injected new vitality into uncovering the structural updates of this mysterious compound.
Today, the synthesis of sophora flavescens is no longer limited to Woodward's original method, but also includes emerging synthetic strategies. How can we achieve efficient synthesis while retaining its structural complexity?
