Synthesis of sesquiterpenes

Tandem cyclization-cycloaddition of diazoketones in the synthesis of sesquiterpenes, possessing 7-oxabicyclo [2.2.1]heptane fragment 97F303. 

This sequence was successfully employed by Thomas [78] for the synthesis of sesquiterpenes such as 3-sinesal (4-232), and by Raucher and coworkers [79] for the synthesis of the germanocrolid (+)-dihydrocostunolide (4-233) (Scheme 4.50). 

Such reactions have also often been used in the synthesis of sesquiterpenes as (+)-epiprecapnelladiene4m) (4.49), ( )-isocomene 462) (4.50) or of hir-sutane derivatives (4.51) 463). 

The fragmentation reaction was applied most successfully in the total synthesis of sesquiterpenes 39). For example, the mesylate (110) underwent fragmentation reaction to provide the ketone (111), which could be converted to (112). The compound (112) was eventually transformed to the isolable mixtures of p-himachalene (113), trans-a-himachalene (114) as well as traHs-y-himachalene (115)40). 

The photoisomerization of 2-(pent-4-enyl)-3-oxycyclohex-2-enones 5 to 6-oxytricyclo[6.3.0.01,6]-undecan-2-ones 6 has been used as a key step for the synthesis of sesquiterpenes containing the bicyclo[6.3.0]undecane carbon skeleton.15 16... 

A silicon-guided boron trifluoride-promoted rearrangement of a 9-trimethylsilyl-5,6-epoxynoreudesmane gave a norspiroaxane as the main product (Scheme 43).70 The spiro product was used as intermediate for the synthesis of sesquiterpenes gleenol and axenol. 

Srikrishna and co-workers have described cyclopentannulation of allyl alcohols by radical cyclizations as, protocols for the synthesis of sesquiterpenes. The total synthesis of 4-epibakkenolide-A 98 wherein two radical annulations were used for key carbon-carbon bond formations is illustrated [95CC469]. Radical cyclizations based on the 5-exo-dig pathway have been used as the key step in the total synthesis of sporothriolide and 4-epi-ethisolide [95TL2661] and in an approach to eriolanin skeleton [95TL2067],... 

Ley et al. also applied this method to the synthesis of sesquiterpenes through a strategy involving a Diels-Alder reaction. Taking into account the effect of conditions and silver counterion on allene isomerization (see Scheme 33), they obtained the diene partner via isomerization of the acetoxyallene produced on treatment of a propargyl acetate with catalytic amount of silver hexafluoroantimonate (Scheme 3.36).57... 

Marin, D. 2001. Biomimetic synthesis of sesquiterpenes from Helianthus annuus. Helibisabonol A. Ms. dissertation. University of Cadiz, Spain... 

Heathcock CH, Graham SL, Pirrung MC, Plavac F, White CT (1979) Total Synthesis of Sesquiterpenes, 1970-1979. In ApSimon J (ed) Synthesis of Natural Products, Vol. V, p. 510. Wiley, New York, Chichester, Brisbane, Toronto, Singapore... 

Direct-defense compounds can be either constitutively present in (specific parts of) the plant or be produced after induction by pathogens or herbivores. The latter compound will be less costly for the plant. For example, elicitor-induced accumulation of the antimicrobial sesquiterpenoid capsidiol correlated with the induction of 5-ept-aristolochene synthase, which is a branch-point sesquiterpene cyclase involved in the synthesis of sesquiterpene phytoalexins (8). In rice Oryza saliva L.), 14 diterpenoid phytoalexins have been identified. All these compounds are accumulated in rice leaves after inoculation with the... 

As part of a synthesis of sesquiterpenes, the sulfone 182 and the allylic halide 183 were coupled (allylic electrophile as well as allylic nucleophile ) to give a mixture of diastereoisomers of 184 that gave the triene 185 on elimination.48 Note that the new double bond is exclusively E. 

The nucleophile does not have to be an enolate orf/to-lithiated aromatics (chapter 7) work well as in this sequence used in the synthesis of sesquiterpene lactones. 2-Methyl furan 45 is lithiated in the one remaining a-position 46 and it adds to the ethyl equivalent of 40 to give the enone 48 in quantitative yield.5... 

An improved synthesis of glutinosone (1) was also accomplished by Masamune and coworkers6 and this was based on procedure developed by Dastur7,8 for the synthesis of sesquiterpenes nootkatone. (Scheme 2) Diels-Alder reaction of 3,6-dihydro-3,5-dimethyl anisole with methyl acrylate in absence of Lewis acids afforded a 1 3 mixture of esters (17) and (18) which were converted to a,(3-unsaturated aldehydes (19) in 77% yield by oxidation with selenium (IV) oxide in dioxane. Wittig reaction of aldehydes under the usual condition yielded the dienes (20) in 63% yield which on being subjected to Grignard reaction with an excess of methyllithium produced tettiary alcohols (21) in quantitative yield. This on treatment with formic acid at room temperature gave bicyclic enone (22) and its formate (23) in 45% and 41% yield respectively. Formates (23) were hydrolyzed to enone (22) in 88% yield. 

Synthesis of 6,12-sesquiterpenolides This section describes the synthesis of sesquiterpenes bearing a lactone moiety between C(6) and C(12). The transformation of the A-ring in santonin to give eudesmanolides, guaianolides, and elemanolides, as well as the modification of the lactone ring is described. Some microbiological transformations of santonin and its derivatives are also described. 

Synthesis of sesquiterpenes that do not contain a lactone moiety. 

Modification of the lactone ring to give a product other than an a-methylene-y-lactone has attracted the synthetic efforts of many researchers in recent years. Ando and coworkers [21] have reported an efficient method for the synthesis of sesquiterpenes possessing C(13)-functionalized endocyclic a,)3-unsaturated-y-lactones such as A (X = CH3, CH2OH, CH2OAC, CHO) and 7-hydroxy-a-methylene-y-lactones such as B (Figure 3). 

SYNTHESIS OF SESQUITERPENES THAT DO NOT CONTAIN A LACTONE MOIETY... 

Cyclopentadiene is used in the manufacture of resins, in the synthesis of sesquiterpenes and camphors, and as a ligand in the preparation of metal complexes. 

Tandem cyclization cycloaddition of diazoketones in the synthesis of sesquiterpenes, possessing 7-oxabicyclo [2.2.1]heptane fragment 97F303. Terpenoids with heterocycHc fragments as bioactive taxoids from Japanese yew Taxsus cuspidata and taxol bios5mthesis 98H(47)1 111. 

Scheme 18.1 Synthesis of sesquiterpenes polygodiol, cinnamolide, drimenin, and isodrimeninol.

An asymmetric intramolecular Michael-aldol reaction which leads to nonracemic tricyclic cyclobutanes is performed by using TMSOTf andbis[(/ )-l-phenylethyl]amine as chiral amine, but only moderate enantioselectivities are reached (eq 68). A similar reaction sequence can also be carried out with TMSOTf and HMDS as base, with (—)-8-phenylmenthol as the chiral auxiliary however, the iodotrimethylsilane-HMDS system is more efficient in terms of yield and diastereoselectivity. The combination EtsN/TMSOTf (or some other trialkylsilyl triflates) has been used to accomplish an intramolecular Michael reaction, which was the key step for the synthesis of sesquiterpene (=E)-ricciocarpin A. ... 

Most evidence supports synthesis of sesquiterpenes in the cytosol/microsomal compartment of plant cells (Threlfall and Whitehead, 1991). The endoplasmic reticulum appears to be the site of FPP synthase (prenyltransferase) and sesqui-... 

The biosynthesis of sesquiterpenes in plants appears to be isolated from that of either monoterpenes or diterpenes. A prenyl transferase isolated from pumpkin Cucurbita pepo, Cucurbitaceae) converts C5 units into FPP, but not into gera-nylgeranyl pyrophosphate (the precursor to diterpenes). Another enzyme from the same source forms C20 terpenoids from C5 units, but does not accumulate lower homologs (also see Chapters 19 and 22). However, because famesyl pyrophosphate synthetase is a branch-point metabolite for the synthesis of sesquiterpenes, triterpenes, and sterols, this enzyme is ubiquitous in plants (Croteau and Johnson, 1985). 

A useful synthesis of sesquiterpene ketones, called cyperones, was accomplished through a modification of the following Robinson annulation procedure (Section 19.7B). Write a mechanism that accounts for each step of this synthesis. 

Scheme 11.32 Hudlicky s synthesis of sesquiterpene (-)-specionin involving the TMSI-promoted rearrangement of fused siloxy VCP 38.

Heathcock C H, Graham S L, Pirrung M C, Plavac F, White C T 1983 The total synthesis of sesquiterpenes, 1970-1979. In ApSimon J (ed) SThe total synthesis of natural products, vol 5. Wiley-Interscience New York, 550 pp... 

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