Modern organic synthesis complex natural products

The term diversity-oriented synthesis (DOS) is relatively new and, as mentioned above, is usually defined as the synthesis of complex, natural product-like molecules using a combinatorial approach and employing the full palette of modern organic reactions. It may be a subject of discussion what exactly qualifies a molecule as being natural product-like [4], and in most cases the similarity to an actual natural product seems reciprocal to the number of synthesized compounds. However, even in less complex cases, the products may be highly substituted polycyclic structures with defined stereochemistry, reminiscent of natural products [19, 20]. In these cases, a moderately complex backbone structure is subsequently modified with a well-established set of selective reactions to introduce diversity. 

The oxidative activation of arenes is a powerful and versatile synthetic tactic that enables dearomatization to give useful synthons. Central to this chemistry are hydroxylated arenes or arenols, the phenolic functions of which can be exploited to facilitate the dearomatizing process by two-electron oxidation. Suitably substituted arenols can hence be converted, with the help of oxygen- or carbon-based nucleophiles, into ortho-quinone monoketals and ortho-quinols. These 6-oxocyclohexa-2,4-dienones are ideally functionalized for the construction of many complex and polyoxygenated natural product architectures. Today, the inherent and multiple reactivity of arenol-derived ortho-quinone monoketals and ortho-quinols species is finding numerous and, in many cases, biomimetic applications in modern organic synthesis. 

Few organic transformations add as much molecular complexity in one step as the Pauson-Khand reaction. This reaction is one of the best examples of how organometallic chemistry is useful in modern organic synthesis, and can serve as a key tool for the synthesis of natural products, in this case those possessing cyclopentane units. The limited scope, low yields and lack of efficient catalytic procedures were serious drawbacks in the past that have been... 

The C-glycosidic linkage is also found in many biologically important natural products such as marine natural toxins and antibiotics as shown in O Fig. 2. Since synthesis of these structurally complex natural products has been a major subject in modern organic synthesis, stere-... 

Nevertheless, no matter how fast the organic synthesis develops, there are still a lot of natural products chemists cannot conquer. The complexities of natural organisms are always beyond our imagination. The exploration of complicated natural products always challenges the wisdom and creativity of organic chemists. Furthermore, the cross fusion of various subjects in modern era put forward new requirements and challenges for chemists working in the field of total synthesis of natural products. It requires them to have not only excellent chemistry skills and visions but also open mind in the new era. It also requires chemists to be able to analyze problem in the views over various fields. 

In the earliest period of complex natural product synthesis, from Robinson s 1917 tropinone synthesis to Eschenmoser and Woodward s 1973 coenzyme synthesis, metal-catalyzed reactions played no great role. In contrast, modern organic syntheses often involve numerous transition metal-catalyzed steps. Main-group compounds, such as BuLi, MeMgBr, or NaBH4, tend to act in stoichiometric quantity as reagents, while the more expensive transition metals, typically complexes of Pd, Rh, or Ru, tend to be used as catalysts and therefore in much lower amounts, for example, 0.1-5 mol% (mmol catalyst per 100 mmol substrate). 

Natural and synthetic products used in medicine and agriculture or as materials in modern technologies are frequently complex organic or organometallic molecules. Syntheses of natural compounds, known as total syntheses, start from the available building blocks and constmct target molecules over many synthetic steps [1-3]. The multistep synthetic route to biologically active compounds not available from natural sources is also called total synthesis. 

---