2.8. Sesquiterpenoid polymers
A novel dimeric guaianolide xylopiana A (40 ), possessing an unprecedented pentacyclo[5.2.1.01,2.04,5′.05,4′]decane-3,2′-dione core, has been found from the leaves of Xylopia vielana , which is one of the main sources of guaiane-type sesquiterpenoid dimers.[63] Furthermore, the case-shaped skeleton of xylopiana A (40 ) is possibly biosynthesized through Diels−Alder cycloaddition of two monomeric guaiane intermediates and then underwent an intramolecular [2 + 2] cycloaddition of a guaianoid dimer (Fig. 10). Some other dimeric guaianolides, hedyorienoid A (41 ), vlasoulamine A (42 ), heliaquanoids A−E (4347 ), and artematrovirenolides A−D (4851 ), have been isolated from four plants includingHedyosmum orientale , Vladimiria souliei , Inula helianthus-aquatica , and Artemisia atrovirens , respectively.[64-67] Structurally, 41possesses an unprecedented heterodimeric structure with two different classes of sesquiterpenoids furnished by forming an unusual 1,3-dioxolane ring. 42 , an unprecedented sesquiterpene lactone dimer featuring a fully hydrogenated pyrrolo[2,1,5-cd]indolizine core, has exhibited neuroprotective activity. 43 represents the first exo -2,4-linked Diels−Alder adduct between a pseudoguaianolide dienophile and a guaianolide diene.4851 are four novel hetero-dimeric [4 + 2] Diels–Alder adducts dimerized from a rotundane-type unit and a guaiane-type monomer.
Fig. 10. Proposed biosynthetic pathway for 40 .
A novel lindenane sesquiterpene dimer spirolindemer A (52 ) and a trimer spirolindemer B (53 ),[68]equipped with oxaspiro[4.5]decane unit, have been discovered from the medicinal plant Chloranthus henryi . 52 showed anti-inflammatory activity by inhibiting the expression of iNOS and COX-2. Chromatography of extracts of plant Chloranthus fortuneiand Chloranthus holostegius afforded the two novel skeletal lindenane sesquiterpene dimers fortunoid A (54 ) and chlotrichene A (55 ), respectively.[69, 70] 54 , the rearranged lindenane dimer, showed moderate antimalarial activities, and 55 , featuring a unique 3/5/6/6/6/6/5/3-fused octacyclic skeleton, possesses a new type of spirocarboncyclic dimeric framework formed by endo -Diels−Alder reaction. In addition, a possible biosynthetic pathway for 54would involve in an intermolecular Diels−Alder cycloaddition by an unidentified [4 + 2] cyclase and oxidative cleavage of the Δ4 double bond.
A novel cadinane sesquiterpene dimer commiphoratone A (56 ),[71] containing a saddle shape skeleton with a unique 6/6/5/5/6/6 heptacyclic architecture, has been isolated from the plant Resina Commiphora , a Chinese medicine for the treatment of blood stagnation. 56 showed significant retardation of lipid metabolism in a concentration-dependent manner. Another compound arteannoide A (57 ),[72]an unusual cadinane dimer featuring a rare fused 6,8-dioxabicyclo[3.2.l]octan-7-one ring system, has also been isolated from the traditional Chinese medicine plant Artemisia annua L. Moreover, a plausible biosynthetic pathway for 57 , involving in aldol and Michael addition reactions, has been proposed in Fig. 11.
Fig. 11. Proposed biosynthetic pathway for 57 .
3. Diterpenoids
Diterpenoids (C20), consisted of four basic isoprene units, are an important group of natural terpenoids with structural diversity, ranking only second to sesquiterpenoids. Biosynthetically, diterpenoids arise from GGPP, which is formed by addition of an IPP to FPP under the catalysis of diterpene synthase. Structurally, they have mainly cyclic carbon skeleton especially tri- and tetracyclic ring systems.[73]The main carbon skeletons and their transformation between each other have been shown in Fig. 12. Importantly, compounds of this family show diverse biological activities, including anti-tumor, anti-renal fibrosis, antimicrobial, and neurotrophic effects.[74-77]In the following pages, diterpenoids (abietane, kaurene, cembrane, etc.) with diverse skeletal types will be introduce
Fig. 12. Classification of the diterpenoids.