Cyclopentane sesquiterpenes

Mono- and bi-cyclic cyclopentanes, known precursors of variety of sesquiterpenes, have been prepared by the acid-catalysed rearrangement of 1-methylcyclo-butylmethanols. An acid-catalysed rearrangement (see Scheme 77) has been found to afford a practical method for converting a bicyclo[4.2.0]octene system (221) into a bicyclo[3.2.1]octene framework (222) in a recent synthesis of verrucarol. ... 

Non-celastraceous sesquiterpene pyridine alkaloids are those compounds which have been isolated from other plants not belonging to the Celestraceae family. Rotundine, for example, has been isolated from Cyperus rotun-dus (Cypraceae). This is a structurally interesting alkaloid because it has a sesquiterpene skeleton containing a cyclopentane ring attached to the pyridine ring . 

Cyclopentane annelation.1 A recent synthesis of the sesquiterpene silphinene (7) used two cyclopentane annelations, both involving conjugate addition of the Grignard reagent derived from 1 in the presence of CuBr S(CH3)2 to an a,/ -enone. Thus 3, obtained as shown, undergoes dehydration to 4. This product was converted to 5, which undergoes a second cyclopentane annelation to give eventually 6, which has the carbon skeleton of 7. 

A number of natural sesquiterpenes like hirsutene 90 or corioline 91 have as their common structural unit a system of linearly fused five-membered rings (Scheme 3.21). The standard pathway of the retrosynthetic analysis of this system involves the search for strategic bonds in one of the rings. A, B, or C, disconnection of which would lead to the simplification of the target molecule and eventually to simple cyclopentane derivatives as available starting materials. As a result, diverse synthetic plans were devised and successfully employed in numerous synthetic studies in this field(see also the set of syntheses described in Section 2.23.2). 

S.J. Danishefsky and co-workers reported the total synthesis of pentacyclic sesquiterpene dilactone, merrilactone A. ° In their approach, they utilized Keck s radical allylation method to achieve the required chain extension. This sidechain was later used to construct one of the cyclopentane rings of the natural product. 

The alkylidene-1,3-dicarbonyl moiety is also a highly reactive enophile. Thus, the Knoevenagel adduct (223) obtained from aldehyde (222) and dimethyl malonate in the presence of piperidinium acetate, cy-clizes by treatment with Lewis acids such as FeCb on AI2O3 exclusively to the rranr-substituted cyclohexane (224 trans.cis > 99.5 0.5 Scheme 44).7 °3 The sesquiterpene veticadinol (225) has been synthesized in enantiomerically pure form by this method.Contrary to the expectation, rranr-sub-stituted cyclopentanes can also be obtained with excellent induced and noninduced dia-stereoselectivities. Similarly, aldehydes containing an allylsilane moiety can be used for a highly stereoselective formation of rran.r-l,2-disubstituted cyclopentanes and cyclohexanes by a Knoevenagel... 

Most of the trends which were apparent in previous years have continued to manifest themselves. The feverish activity directed towards the synthesis of the hirsutane class of sesquiterpenes has not abated and other natural products containing annulated cyclopentane rings have also proved popular synthetic targets. In the field of steroid synthesis. Stork and his co-workers have developed an outstandingly elegant approach to 11-oxygenated steroids. 

The fused cyclopentane 25 has been prepared by radical cyclization via deoxygenation of 24 (Scheme 4). This ring system is a carbocyclic analogue related to the A/B ring system of the cytotoxic sesquiterpene, (+)-eremantholide. 

One early example was reported by Chatteijee in 1979 for stereospecific synthesis of the sesquiterpene isocomene by transannular cationic cyclization. The acid-catalyzed cyclization of epoxide 152 through transannular participation of the remote double bond led to the formation of 153 (Scheme 20.37), which was further transformed to isocomene. The reaction was stereoselective since formation of any other diastereomers will lead to the formation of much strained polycyclic systems with trans-fased cyclopentanes. 

The carbon skeleton of capnellane, formed from three joined cyclopentanes with an angular methyl group and an exocyclic methylene, is dosely related to that of hirsutane, which has the same characteristics and which is one of the most widespread sesquiterpenic skeletons in fungi (Ayer and Browne, 1981). 

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