1 Introduction
Lactones constitute one of the most important classes of compounds in organic
chemistry, and they are generally classified into four main categories such as
β-lactones, γ-lactones, δ-lactones, and macrolactones [1, 2]. Among these lactones,
the δ-lactone moiety is a common structural subunit present in many natural
products, including those isolated from insects, fungi, marine organisms, and plants
[3–5]. Natural products containing the δ-lactone framework have been shown to
exhibit a wide range of biological activity [6–11]. For example, discodermolide
1 [4, 12, 13] (Fig. 1), a polypropionate-derived marine natural product isolated from
the Caribbean sponge Discodermia dissoluta, exhibits potent immunosuppressive
activity comparable with FK506 and rapamycin. Similarly, mevinolin 2 (lovastatin)
[14, 15] and compactin 3 [16, 17] are highly potent inhibitors of 3-hydroxy-3methylglutaryl coenzyme A (HMG CoA) reductase and are effective in lowering
blood plasma cholesterol levels. The β-hydroxy-δ-lactone moiety is the key structural feature of these inhibitors and essential for inhibition as it closely resembles
the HMG portion of the enzyme. Another interesting compound with the δ-lactone
backbone is the (+)-Prelog–Djerassi lactonic acid 4, which was isolated independently by Prelog [18] and Djerassi [19] as a key degradation product of the
macrolide antibiotics pikromycin and narbomycin and methymycin and
neomethymycin, respectively. It has not only provided essential information in
the structural elucidation of these antibiotics but has also served as a synthon in
their synthesis. Pseudolaric acids A, 5, and B, 6, were isolated in 1965 from the bark
of Pseudolarix kaempferi Gordon [20–24], and the extract from root bark of
P. kaempferi has been used as a Chinese herbal medicine called tujinpi for the
treatment of fungal infections. Pseudolaric acid B is a potent antifungal, antifertility, and cytotoxic agent and has also shown significant activity against multidrugresistant cancer cell lines. Similarly, (À)-iridolactone 7 [25, 26] (Fig. 1) isolated
from Pedicularis and Vitex plants is used as folk medicine in Asia. Ricciocarpins A,
8, and B, 9, are two novel sesquiterpene lactones isolated from an axenic culture of
the European liverwort, Ricciocarpos natans (Ricciaceae) [27–30]. These two
natural products have been shown to exhibit high molluscicidal activity against
the water snail Biomphalaria glabrata, a vector of schistosomiasis.
Mevalonolactone 10 [31, 32], the lactone form of mevalonic acid, is an important
intermediate in biosynthetic pathways leading to sterols, carotenoids, terpenes, and
other isoprenoids. Invictolide 11 was isolated by Rocca et al. in 1983 as one of the
three lactones that function as the queen recognition pheromone of the red imported
fire ant Solenopsis invicta Buren [3]. There are also several insect pheromone
δ-lactones such as lactone 12, the proposed pheromone from Vespa orientalis
[33], and δ-lactone 13 present in the white butterfly Idea leuconoe
[34]. (3R,4S,5S,9S)-3,5,9-Trihydroxy-4-methylundecanoic acid δ-lactone 14 [35,
36], a novel pentaketide lactone, is an example of δ-lactones obtained through
98
K. Palanichamy and K.P. Kaliappan
Lactones constitute one of the most important classes of compounds in organic
chemistry, and they are generally classified into four main categories such as
β-lactones, γ-lactones, δ-lactones, and macrolactones [1, 2]. Among these lactones,
the δ-lactone moiety is a common structural subunit present in many natural
products, including those isolated from insects, fungi, marine organisms, and plants
[3–5]. Natural products containing the δ-lactone framework have been shown to
exhibit a wide range of biological activity [6–11]. For example, discodermolide
1 [4, 12, 13] (Fig. 1), a polypropionate-derived marine natural product isolated from
the Caribbean sponge Discodermia dissoluta, exhibits potent immunosuppressive
activity comparable with FK506 and rapamycin. Similarly, mevinolin 2 (lovastatin)
[14, 15] and compactin 3 [16, 17] are highly potent inhibitors of 3-hydroxy-3methylglutaryl coenzyme A (HMG CoA) reductase and are effective in lowering
blood plasma cholesterol levels. The β-hydroxy-δ-lactone moiety is the key structural feature of these inhibitors and essential for inhibition as it closely resembles
the HMG portion of the enzyme. Another interesting compound with the δ-lactone
backbone is the (+)-Prelog–Djerassi lactonic acid 4, which was isolated independently by Prelog [18] and Djerassi [19] as a key degradation product of the
macrolide antibiotics pikromycin and narbomycin and methymycin and
neomethymycin, respectively. It has not only provided essential information in
the structural elucidation of these antibiotics but has also served as a synthon in
their synthesis. Pseudolaric acids A, 5, and B, 6, were isolated in 1965 from the bark
of Pseudolarix kaempferi Gordon [20–24], and the extract from root bark of
P. kaempferi has been used as a Chinese herbal medicine called tujinpi for the
treatment of fungal infections. Pseudolaric acid B is a potent antifungal, antifertility, and cytotoxic agent and has also shown significant activity against multidrugresistant cancer cell lines. Similarly, (À)-iridolactone 7 [25, 26] (Fig. 1) isolated
from Pedicularis and Vitex plants is used as folk medicine in Asia. Ricciocarpins A,
8, and B, 9, are two novel sesquiterpene lactones isolated from an axenic culture of
the European liverwort, Ricciocarpos natans (Ricciaceae) [27–30]. These two
natural products have been shown to exhibit high molluscicidal activity against
the water snail Biomphalaria glabrata, a vector of schistosomiasis.
Mevalonolactone 10 [31, 32], the lactone form of mevalonic acid, is an important
intermediate in biosynthetic pathways leading to sterols, carotenoids, terpenes, and
other isoprenoids. Invictolide 11 was isolated by Rocca et al. in 1983 as one of the
three lactones that function as the queen recognition pheromone of the red imported
fire ant Solenopsis invicta Buren [3]. There are also several insect pheromone
δ-lactones such as lactone 12, the proposed pheromone from Vespa orientalis
[33], and δ-lactone 13 present in the white butterfly Idea leuconoe
[34]. (3R,4S,5S,9S)-3,5,9-Trihydroxy-4-methylundecanoic acid δ-lactone 14 [35,
36], a novel pentaketide lactone, is an example of δ-lactones obtained through
98
K. Palanichamy and K.P. Kaliappan