Diterpenes C20

The diterpenes arise from geranylgeranyl diphos-phate (GGPP), which is formed by addition of a further IPP molecule to farnesyl diphosphate in the same manner as described for the lower terpenoids (Figure 5.41). One of the simplest and most important of the diterpenes is phytol (Figure 5.42), a reduced form of geranylgeran-iol, which forms the lipophilic side-chain of the chlorophylls, e.g. chlorophyll a (Figure 5.42). Related haem molecules, porphyrin components farnesyl PP (FPP)

allylic cation

allylic cation

VV OPP

Hr H

electrophilic addition gives tertiary cation

VV OPP

Hr H

stereospecific loss of proton

geranylgeranyl PP (GGPP)

Figure 5.41

phytol vitamin K1 (phylloquinone)

phytol

vitamin K1 (phylloquinone)

Phytyl Chain Chlorophyll

chlorophyll a

chlorophyll a

Figure 5.42

of haemoglobin, lack such lipophilic side-chains. Available evidence suggests that geranylgeranyl diphosphate is involved in forming the ester linkage, and the three reduction steps necessary to form the phytol ester occur after attachment to the chlorophyll molecule. A phytyl substituent is also found in vitamin K1 (phylloquinone) (Figure 5.42), a naphthoquinone derivative found in plants, though other members of the vitamin K

group (menaquinones) from bacteria have unsaturated terpenoid side-chains of variable length. The phytyl group of phylloquinone is introduced by alkylation of dihydroxynaphthoic acid with phytyl diphosphate and a similar phytylation of homogen-tisic acid features in the formation of the E group vitamins (tocopherols). These compounds are discussed further under shikimate derivatives (see page 158).

cyclization by electrophilic addition cyclization by electrophilic addition

Taxaceae Diterpenes
Figure 5.43

Cyclization reactions of GGPP mediated by car-bocation formation, plus the potential for Wagner -Meerwein rearrangements, will allow many structural variants of diterpenoids to be produced. The toxic principle 'taxine' from common yew (Taxus baccata; Taxaceae) has been shown to be a mixture of at least eleven compounds based on the taxadiene skeleton which can be readily rationalized as in Figure 5.43, employing the same mechanistic principles as seen with mono- and sesqui-terpenes.

Although these compounds are sometimes classified as diterpenoid alkaloids, the nitrogen atom is not incorporated into the diterpene skeleton, as exemplified by taxol (paclitaxel)* (Figure 5.43) from Pacific yew (Taxus brevifolia )*. The side-chains in taxol containing aromatic rings are derived from shikimate via phenylalanine. Taxol is an important new anticancer agent, with a broad spectrum of activity against some cancers which do not respond to other agents.

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