**1. Introduction**

The flavonoid Diels‐Alder natural products are mainly found from the families of Moraceae and Zingiberaceae. Since the majority of these compounds are discovered from the Moraceae, they are often referred as mulberry Diels‐Alder flavonoids or mulberry Diels‐Alder type adducts. These secondary metabolites exhibit promising biological activities against hypertension, HIV, tuberculosis, anti‐inflammation and cancers [1–7]. Thus far, more than 140 of these Diels‐Alder type flavonoids have been discovered from nature (**Figure 1**). The structural complexity and promising bioactivities of these flavonoid Diels‐Alder natural products have stimulated research interest into their biosynthesis and chemical synthesis.

The Diels‐Alder type flavonoids are considered to be formed through an enzymatic Diels‐Alder reaction between a dehydroprenyl diene and a chalcone dienophile (**Scheme 1**) [8]. The diene is usually derived from a flavonoid, such as flavone, flavanone, flavonol, flavanonol, or from a

**Figure 1.** Examples of flavonoid Diels‐Alder natural products.

monoterpene, such as myrcene and β‐*trans*‐ocimene. The dienophile of this class of Diels‐Alder compounds is exclusively derived from a chalcone derivative. Subsequent oxidation and cycli‐ zation steps of these flavonoid Diels‐Alder adducts can result in more complex structures. The Diels‐Alder adducts bearing the *cis‐trans* stereochemistry on the cyclohexenyl ring would be derived through an *endo* transition state (**12**), whereas the *trans‐trans* stereochemistry arises

**Scheme 1.** Stereochemistry on the cyclohexene ring of flavonoid Diels‐Alder natural products.

from the *exo* transition state (**13**) (**Scheme 1**) [8]. The stereochemistry of these adducts, includ‐ ing the absolute configuration on the cyclohexene ring, has been explicitly confirmed by circu‐ lar dichroism (CD) spectroscopic evidence [9] and X‐ray crystallographic analysis [10, 11]. The unique structural features and diverse activities of these adducts have recently aroused much interest of synthetic and medicinal chemistry. The main topics addressed in this chapter are biosynthesis and biomimetic synthesis of flavonoid Diels‐Alder natural products and about 40 references are cited. As the flavonoid Diels‐Alder natural products are composed of a diverse family of secondary metabolites, other subclasses where the dienophile is not a chalcone (e.g. mongolicin B, ‐E, sanggenon B, ‐R, ‐S, dimoracin, mulberrofuran H, meroterpene, pauferrol A derivatives, etc) are not covered in this chapter.
