Monoterpenes cyclopropane

Chrysanthemic acid (1) consists of ten carbons, suggesting that it is a monoterpene. The cyclopropane ring of the acid moiety is a feature of pyrethrins. Rivera et al. isolated chrysanthemyl pyrophosphate synthase (CPPase or alternatively referred to as chrysanthemyl diphosphate synthase) underlying the formation of chrysanthemyl pyrophosphate (16) containing a cyclopropane ring from two molecules of dimethylallyl pyrophosphate (15) (DMAPP) and the gene thereof [21]. They found that the reaction involves the cF-2-3 cyclopropanation of DMAPPs in a non-head-to-tail manner. 

Thujane-type monoterpenes, unusual monoterpenes with a cyclopropane ring in a bicyclo[3.1.0] skeleton, are formed from the terpinen-4-yl cation directly or via the sabinyl cation. Important members include a-thujene 52, sa-binene 53, the cis isomer 54 of sabinene hydrate, sabinol 55, sabinylacetate 56, a-thujone 57, -thujone 58 and isothujanol 59 (Structure 4.13). 

Carane-type monoterpenes possess a cyclopropane ring in a bicyclo[4.1.0] skeleton. d-3-Carene 10 is a common constituent in various essential oils. 

The remarkably efficient cyclopropanation reaction with an in-situ-generated zinc carbenoid, Eq. (61) provided a straightforward synthesis of the monoterpene sabinene (42) starting from the P-keto ester 41 [58],... 

Cuprates add directly to the carbonyl group however, promoted by the Lewis acid BF3, ring cleavage is facilitated and a 1,5-addition affords the bicyclic compound 32. This mode of cyclopropane opening is a key step in the short preparation of the monoterpene eucalyptol22). 

Pyrethrum (Chrysanthemum) dnerarifolium (Asteraceae) namely cinerin I (CMC cineralone ester), cinerin II (CDC monomethyl ester cinerolone ester), pyrethrin I (CMC pyrethrolone ester) and pyrethrin II (CDC monomethyl ester pyrethrolone ester). The chrysanthemum carboxylic acids are cyclopropane-based monoterpenes and cineralone and pyrethrolone are cyclopentanone monoterpene alcohols. The pyrethrins (and their insecticidal synthetic derivatives) are toxic to insects through keeping cell membrane voltage-gated Na+ channels open and thus impairing neurotransmission. 

Additional chemical diversity of monoterpenes is apparent from the natural occurrence of their bicyclic analogs that bear cyclopropane (carane and thujane types), cyclobutane (pinane type), and cyclopentane (camphene/bornane, isoeamphane and fenchone types) rings (Figs. 6 and 7). The carane type of bicyclic monoterpenoids in plants is represented by (+)-3-carene... 

C]-mevalonic acid (56a) in Pinus palustris or P. sylvestris showed that the Relabeling is predominantly at (4) . Namely, the C(4) of the monoterpene is derived from C(2) of mevalonic acid (56) rather than C(4) as had been assumed and therefore, the cyclopropane ring formation must be accompanied by a double bond migration if a-car-3-ene (61) is indeed dervied from a-terpinyl ion (62) or its biosynthetic equivalents. 

In this section we analyze information about metabolic cleavage or breakdown of cyclopropane rings in three instances the biosynthesis of irregular monoterpenes, the ringopening of cycloartenol (20) derivatives, and the metabolic opening of 1-aminocyclopropane-1-carboxylic acid (ACPC) (9) by two quite distinct fragmentation routes. We will not explicitly discuss the processing of presqualene pyrophosphate (77) and prephytoene pyrophosphate (89) to squalene (76) and phytoene (88) respectively, since those transformations have already been dealt with in Section II. 

A. Degradation of Cyclopropane Rings in the Biosynthesis of Irregular Monoterpenes... 

The preferred rotational conformations of acetyl and formyl groups can be predicted by temperature-dependent c.d. measurements, and the technique has been applied to some monoterpene aldehydes. The sign of the Cotton effect has been related to the chirality of a series of Ti-molecular complexes of monoterpene (and other) hydrocarbons with tetracyanoethylene. Inconclusive results found with (-h )-sabinene were ascribed to complexation with the cyclopropane ring. °... 

Chrysanthemol from the leaves of Artemisia ludiviciana (Asteraceae) belongs to the cyclopropane monoterpenes Cinerins, jasmolins and pyrethrins (all including derivatives 1 and 11) are esters of /rara-chrysanthemic and pyrethric acid with terpenoid hydroxypentenones such as cinerolone, jasmolone and pyrethrolone. These are the active insecticidal constituents of pyrethrum recovered from dried flowers of several Chrysanthemum species (e.g. Chrysanthemum cinerariaefolium, Asteraceae). Some synthetic esters of chrysanthemic acid are also applied as insecticides. 

Bicyclic cyclopropanes carane and thujane, bicyclic cyclobutane pinane, and bi-cyclo[2.2.1]heptanes such as camphane, isocamphane and fenchane are the most important skeletons of naturally occurring bicyclic monoterpenes... 

Of these two options, the second has a possible problem of regioselectivity during the rearrangement, as shown in the Fig. 9. As we have shown [30], this regioselectivity is determined by migratory aptitudes and can be exclusive, as presented below (Fig. 10). We have also investigated the cyclopropanation/ intercyclic bond cleavage of simple monoterpenes as an easy access to enan-tiopure 1,4-methyl-isopropyl substituted cycloheptenones, as shown also in Fig. 10 [31-33]. 

Car-3-ene is the only commonly occurring monoterpene with the carane skeleton. Degradation of (+)-car-3-ene derived from [2- ]mevalonate in Pinus spp. indicates that, if this compound is derived via the hypothetical intermediate a in Fig. 5, then formation of the cyclopropane ring is accompanied by migration of the double bond of this intermediate (Banthorpe and Ekundayo, 1976). 

With respect to the biosynthesis of bicychc monoterpenes, several pathways are known. For example, the men-thyl cation C can undergo a deprotonation in position 5 of the ring followed by an immediate cyclopropane formation to access the carane-type bicyclic compound 41. 

Alternatively, the pathway toward the cyclopropane-containing thujane-type monoterpenes utilizes the terpinen-4-yl cation E, which can form the thujyl cation F via a t-cation cycliza-tion. Subsequent deprotonation then gives the bicyclic sabi-nene (42), which can also be further metabolized to thujone (43) (Scheme 6.8). 

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