Chiral sesquiterpenes synthesis

Semen, reactive oxygen species, 612 Sensorial quaUty appreciation, oxidation stabihty, 664 Semm protein oxidative damage, 614 see also Human seram Sesquiterpenes, stractural chemistry, 133-6 SET see Single electron transfer Sharpless epoxidation, allylic alcohols, 789 Shelf durability, peroxide value, 656 Ship-in-the-bottle strategy, chiral dioxetane synthesis, 1176-7... 

Highly uMtr-diastereofacial selective cycloaddition of isoprene (2) with 4-isopropyl-2-cyclohexenone allowed a short regiocontrolled and stereocon-trolled synthesis [13] of jS-cadinene and (y2-cadinene, Scheme 3.3). High anti-diastereofacial selectivity also occurs in the Diels-Alder reaction of optically active cyclohexenones 6-9 (Figure 3.2), readily available from the chiral pool, with open chain dienes [14-16]. Their cycloadducts are valuable intermediates in the synthesis of optically active sesquiterpenes in view of the easy conversion of the gem-dimethylcyclopropane and gem-dimethylcyclobutane in a variety of substituents. 

Rearrangement of dienynols to vinylallene sulfoxides. A few years ago, Oka-mura et al. (11, 39) reported the rearrangement of a dienynol to an allenyldiene with transfer of chirality of the propargylic alcohol. This rearrangement has now been used for an enantioselective synthesis of a sesquiterpene, (+ )-sterpurene (3).Thus reaction of the optically active propargylic alcohol 1 with C6H,SC1 at 25° results in a vinylallene (a) that cyclizes to the optically active sulfoxide 2. Nickel-... 

Caryophyllenes, as an example of two naturally occurring isomeric sesquiterpenes containing a medium-sized ring, in which the success of the total syntheses lies in the stereoselective control of a chiral centre, in a common synthetic key intermediate, which governs the configuration (JE or Z) of the double bonds present in each one of the two isomers. In this context, a brief reference to Cecropia Juvenile Hormone synthesis by the Syntex group, as well as to Johnson s cationic cyclisation of unsaturated polyolefins to fused polycyclic compounds, is made. 

With Tartrate-Derived Chiral 1,4-Diol/Ti Complexes A catalytic asymmetric Diels-Alder reaction is promoted by the use of a chiral titanium catalyst prepared in situ from (Pr O TiC and a tartrate-derived (2.R,3.R)-l,l>4,4-tetraphenyl-2,3-0-(l-phenylethylidene)-l,2,3,4-butanetetrol. This chiral titanium catalyst, developed by Narasaka, has been successfully executed with oxazolidinone derivatives of 3-borylpropenoic acids as P-hydroxy acrylic acid equivalents [40] (Eq. 8A.21). The resulting chiral adduct can be utilized for the first asymmetric total synthesis of a highly oxygenated sesquiterpene, (-i-)-Paniculide. 

In addition, allenes can act as the olefinic part of the reaction [32], Al-lenynes like 12 may react with both double bonds. Brummond established the substitution patterns for the reaction with either the external or the internal bond of the allenic fragment, that give products with different ring sizes (13— 14) [33]. This group has applied these studies to the synthesis of hydroxy-methylfulvalene (17), a potent anticancer agent related with illudines, a natural sesquiterpene family. The key step was the synthesis of 16 from 15 with a PKR mediated by molybdenum carbonyl (Scheme 6) [34,35]. In addition they have developed an asymmetric version of the reaction. They have transferred efficiently chirality from a non-racemic allene to an a-alkylidene and an a-silylidene cyclopentenone in a molybdenum mediated reaction [36-38]. 

Three new chirality centers are formed with high enantio- and complete diastereoselectivity in the course of the reaction of the enol triflate 37 to the bicyclo [3.3.0]octane derivative 38 (Scheme 11) [15]. In this transformation, the intermediate 39, formed by oxidative addition, leads to the cationic palladium-7r-allyl complex 40, which is finally converted to the isolated product 38 by regio- and diastereoselective nucleophilic addition of an acetate anion. The bicyclic product 38 is of interest as a building block for the synthesis of capnellene sesquiterpenes. 

Uvidins are attractive chiral starting materials for the synthesis of highly oxidized biologically active drimane-like sesquiterpenes as demonstrated by the syntheses of natural (-)-cinnamodial (115) and (-)-cinnamosmolide (116) from uvidin A (3.14),... 

A useful synthesis (ref.ll)of patchouli alcohol, an important fragrant constituent of patchouli oil, from (+)-camphor, that onetime important natural product which was employed as a plasticiser for nitrocellulose (itself a semi-synthetic polymer), was complicated by structural revision of the sesquiterpene alcohol. Dihydrocarvone (14) obtained by saturation of the ring double bond in carvone, a major constituent of oil of spearmint has been employed for two very different sesquiterpenes, the ketone campherenone (15) and the alcohol, occidentalol (16). In the first case an enol acetate was converted to a bicyclic intermediate by earlier established methodology and the route emulated a plausible biogenetic sequence giving racemic campherenone (ref.12) as shown. Any chirality in (14) is apparently lost. 

Interest in die synthesis of enantiomerically pure compounds is also significant since both enantiomers of the same product often show distinctly different biological activities. In recent decades an enormous effort has been focused on the development of new methods for the stereoselective synthesis of natural products. These methods include a number of approaches for achieving enantioselective transformations of achiral substrates by using chiral auxiliaries, chiral reagents, or chiral catalysts [3]. However, from the range of different synthetic approaches available, the most useful for the synthesis of enantiomerically pure sesquiterpenes is still the hemi-synthesis from readily available natural sesquiterpenes. 

Abstract Planar-chiral ri -arene-Cr(CO)3 complexes represent highly valuable buUdlng blocks for the dlastereo- and enantloselectlve synthesis of complex natural products and related bloactlve compounds. Highly original and competitive overall syntheses of various classes of natural products, such as sesquiterpenes, diterpenes, alkaloids and compounds with axial chirality, have been developed. In certain cases, the whole strategy is based on arene chromium chemistry and the various chemical and stereochemical effects of the metal unit are exploited In several subsequent transformations. Cationic Cp-ruthenium complexes allow arylether formation by Sj Ar reactions and have found application in the synthesis of glyco-peptide antibiotics. 

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. ... 

Caryophyllene. Caryophyllene, 8, is a sesquiterpene that presents the challenge of the synthesis of fused small (four-membered) and medium (nine-membered) rings. The functionality is not complex, since only alkene groups are present. There are two chiral centers and one alkene unit that must be constructed with trans stereochemistry. The successful synthesis is outlined in Scheme 10.12. Several of... 

The first total synthesis of the sesquiterpene hydrocarbon ( + )-a-amorphene (zizanene) (256) has been achieved by the interesting use of an oxy-Cope rearrangement to introduce all three chiral centres, in the correct relative configuration, in one step. The key intermediate (254) thus afforded (255 60%), which was readily transformed into (256). The Cope rearrangement of enrfo-5-isopropenyl-2-norbornene to cis-5-methyl-3a,4,7,7a-tetrahydro-177-indene has been subjected to close scrutiny observed and calculated n.m.r. chemical shifts for both endo- and exo-isomers of the reactant and of the product are tabulated to confirm structures and to eliminate isomeric... 

In a total synthesis of the ginseng sesquiterpene (—)-j8-panasinsene, ketone methylenation with optical resolution was reported [12a]. Thus, a kinetic resolution was operative in the reaction of the lithium carbanion of chiral sulfoximide 201 with the racemic ketone 200, giving a separable mixture of two compounds, (+)-202 and (+)-203. The latter diastereomer was converted to the natural product. 

One should keep in mind that further functionalization can also be built-in function on the substrate itself. Thus, for instance, acetals upon acidic hydrolysis allow an intramolecular aldolization-crotonization. This transformation produces chiral bicyclic a,p-unsaturated compoimds. These compounds are important intermediates for the synthesis of sesquiterpene derivatives. For instance, this procedure has been recently used in the alternative synthesis of axane derivatives [87] isolated from the marine sponge Axinella cannabia (Scheme 22) [33]. 

Honda, T., Ishige, H., and Nagase, H. (1994) Chiral synthesis of a trinorguaiane sesquiterpene, davukerin A. J. Chem. Soc. Perkin Trans. I, 3305-3310. 

Photo-mediated asymmetric synthesis of (2)-cuparene has been studied by Grainger and Patel (2003). In this procedure, generation of a benzylic quaternary stereocenter via the photo-mediated cyclization of a chiral (aminobutyl) styrene followed by a microwave-assisted Cope elimination led to a total synthesis of the sesquiterpene... 

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