Copalyl pyrophosphate

The mode of action of CCC is attributed to the inhibition of / Akaurene synthetase A, the enzyme that drives the biosynthesis of geranyigeranylpyrophosphate by copalyl pyrophosphate to /-kaurene. The compound is registered in Europe to control lodging and is registered with the EPA. 

The retardation effect of all these substances can be reversed by gibberellins. Furthermore, it has been possible, in the case of some of these substances, to detect precisely the point of attack or site of action in the gibberellin biosynthesis sequence. As can be seen from Figure 3, it is assumed that the onium compounds inhibit the cyclization of geranylgeranyl pyrophosphate to copalyl pyrophosphate (7), whereas it has been demonstrated in cell-free systems that pyrimidines, norbornenodiazetines, and triazoles inhibit the sequential oxidation of ent-kaurene to ent-kaurenoic acid (fj, 9). 

Biosynthesis (Chapter 6).— E>etailed studies have been reported with individual enzymes responsible for the early stages of terpenoid biosynthesis. The mechanism whereby two molecules of famesyl pyrophosphate couple to furnish squalene is still uncertain and the structure of the C30 pyrophosphate intermediate isolated by Rilling in 1966 remains elusive. The genesis of the monoterpenoid portion of the indole alkaloids has been intensively studied. Of special interest was the discovery of the bismonoterpenoid foliamenthin, which is a derivative of the indole alkaloid precursor secologanin. The biosynthesis of the gibberellins has received detailed attention on both sides of the Atlantic. nr-kaurene, the parent, is formed via geranylgeranyl pyrophosphate and enr-copalyl pyrophosphate and this seems to follow a... 

Momilactones arise from GGPP via 9,pH-labdadienyl pyrophosphate (66) and 9-3H-pimara-7,15-diene (67), whereas oryzalexins arise via copalyl pyrophosphate (35) and sandaracopimaridiene (36). Both groups of diterpenes appear to be synthesized in the cytosol. Only kaurene is found in tissue not attacked by fungi. Chitin proved to be the best elicitor of momilactones in cell culture (West et al., 1990). Chitinase probably breaks down the chitin to active fragments (West et al., 1990). Both types of phytoalexins from rice are probably important in disease resistance, but the relative importance of each has not been assessed (West et al., 1990). 

Fig. 2. The proton-initiated cyclization of GGPP to copalyl pyrophosphate involving transient car-bocationic intermediates...

The diterpene synthase copalyl diphosphate synthase (CDP) is one of the most studied type B synthases. It forms the bicycUc intermediate (-)-copalyl pyrophosphate ((-)-CPP) or its diastereomer (+)-copalyl pyrophosphate ((+)-CPP) from GGPP. Several CDPs are expressed in rice OsCycl forms (+)-CPP, while OsCyc2 and OsCPSl form (-)-CPPs. OsCPSl is believed to be involved in gibberellin biosynthesis and OsCyc2 in diterpene phytoalexin biosynthesis [31],... 

Prisic et al. 2004). The momilactones and oryzalexin S, however, derive from an unusual diastereomeric labdane diphosphate 9,10-sy -copalyl pyrophosphate 53 (Mohan et al. 1996). The normal chair-chair conformational folding of GGPP disfavours the formation of syn-CPP compared with (+)-or (-)-CPP as its formation would require an unfavourable axial placing of the bulky sidechain, so it is assumed that the formation of syn-CPP must proceed via a chair-boat conformational arrangement of GGPP as shown in Figure 3.19. 

Bie stereochemistry of the cyclizatitHi in the biosynthesis of ent-sanadaracopimaradiene (33) has been examined with an enzyme system diich was prepared from Rioinus communis. Incubation of D(s)-1- 3s ylgeranyl pyrophosphate (3I) produced (b) - D 6 1-ent-3andaracopimaradiene (33), showing that the Sjj cyclization of the intermediate copalyl pyrophosphate (52) occurs wi-tti tine anti stereochemistry. Similar results have been obtained in the stereochemistry of tire allylic displacement of a pyrophosphate in the biosynthesis of virescenol B (34), It has also been suggested that the cyclization of copalyl pyrophosphate to ent-kaurene (55) follows the same anti pathway. 

Copalyl pyrophosphate (235-OPP) has been demonstrated to be a key branching point in the biosynthesis of tricyclic and tetracyclic diterpenes 24, 300, 308). It, therefore, seems likely that A -labda-dienyl pyrophosphate (244-OPP) is the precursor to the corresponding enantiomeric diterpenes as shown in the biogenetic scheme below (Scheme 24). Beyond the existence of both enantiomeric series of these tricyclic diterpenes, there is a further stereochemical diversity which results from the cyclization of (235-OPP) and (244-OPP) to sets of stereoisomers epimeric at the new quaternary carbon at C13, e.g., pimaric acid (246) and sandarocopimaradiene (247). 

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