Monoterpenes, methylcyclopentanoid

Methylcyclopentanoid monoterpenes are a group of isoprenoids characterised by the presence in their skeleton of a cyclopentanoid residue. Both hydrophilic and hydrophobic compounds are known (refs 1-3 ), which may be both volatile and non volatile. Products of alkaloidal nature (ref 4 ) are also included in this family. 

Methylcyclopentanoid monoterpenes represent key intermediates of monoterpene metabolism of this type in fact, starting from this skeleton, the typical biotransformation of the cyclopentanoid residue begins, as an oxidative cleavage. 

Another aspect of methylcyclopentanoid monoterpenes is their biological role for the organisms which biosynthesise them. They are in fact often involved in the plant/insect and in the plant/plant biochemical interactions the biochemical role of these compounds has been extensively studied in recent years and the role of methylcyclopentanoid monoterpenes in plant-animal and plant-plant interactions has been demonstrated (ref 9 ). 

Methylcyclopentanoid monoterpenes and their metabolites also show several biological activities in man and animals (ref 10). 

In this article the stereoselective syntheses of methylcyclopentanoid monoterpenes are reviewed. The chemical procedures performed for the synthesis of glycosidic and non glycosidic iridoids will be presented. 

Methylcyclopentanoid monoterpenes are structurally characterised by a (1R,6S) 3-oxobicyclo[4.3.0]nonane moiety. 

The biogenesis of methylcyclopentanoid monoterpenes has been carefully studied allowing the key steps of the process to be depicted (ref.s 11-13). 

The methylcyclopentanoid monoterpenes arise from geranyl-PP via an intramolecular stereocontrolled Mannich type condensation of a dialdehydic or a trialdehydic intermediate, as shown in fig.4. The resulting cyclopentanaldehydic compound has been named iridodial or iridotrial, depending on the nature of the biosynthesized compound and of its biogenetic pathway. 

Iridodial and iridotrial intermediates can arise by different biogenetic pathways, giving rise to different groups of methylcyclopentanoid monoterpenes. 

The hemiacetalic C-2 fimction can be blocked by a sugar residue, affording the methylcyclopentanoid monoterpenes known as glycosidic iridoids. Otherwise the same function can be esterified giving rise to the non-glycosidic iridoids of plumeria or valeriana-type ( fig.6 ). 

In the end, it is necessary to cite, in this biogenetic discourse, the secoiridoid group which is derived from methylcyclopentanoid monoterpenes, even if it does not maintain the characteristic methylcyclopentanoid moiety. Secoiridoids arise, in fact, from the oxidative opening of the cyclopentane ring of both glycosidic or non-glycosidic iridoids by cleavage of the C-8/C-9 bond. 

The compound 18 gave rise to the more stable hemiacetalic structure of verbenalol 19, corresponding to the methylcyclopentanoid monoterpenic structure of verbenalin. 

The Claisen rearrangement - nitrile oxide cycloaddition sequence has been adapted to the synthesis of methylcyclopentanoid monoterpenes by Curran et al. (ref. 31-32 ). 

The 2-hydroxy-3-oxobicyclo[4.3.0]nonane-type skeleton, typical of methylcyclopentanoid monoterpenes, has been then constructed in a stereospecific and regiospeciflc manner. Successive steps can be designed according to the target molecular moiety. 

Different approaches have been proposed for the stereoselective synthesis of methylcyclopentanoid monoterpenes with nepetalactone-type skeleton (3-oxobicyclo[4.3.0]nonan-2-one-type) and iridomirmecin-type skeleton (3-oxobicyclo[4.3.0]nonan-4-one-type). We will divide the discussion on the basis of the key reactions used in the S5mthetic strategy. 

In schemes 20 and 21 are depicted the strategies for the stereoselective transformations of the key intermediate 96 in the methylcyclopentanoid monoterpenes with iridomyrmecin- and nepetalactone-type skeleton. 

Fig. 20.10. Methylcyclopentanoid monoterpenes from larval secretions of Chrysomelini.

---