Synthesis Of Sesquiterpenes Research Articles

Assembly of tricyclic compounds that include the spiro[4.4]nonane subunit

Spiroannulation of ketals derived from unsaturated cyclohexenone derivatives by the Lewis acid-catalyzed reaction of 1,2-bis((trimethylsilyl)oxy)cyclobutene 5 led to spiro[4.5]decene-diones 9 and 30. These were transformed into spiro[4.4]nonene derivatives 25 and 35/36 via similar sequences involving ozonolysis and aldol ring reclosure. Reduction of an annular double bond allowed facile closure of a third ring, also by an aldol reaction. This work led to a single oxygenated angular triquinane 28 from 9, and to the tricyclo[6.2.1.01,5]undecane derivative 41 from 30. An oxatricyclo[5.3.1.01,5]undecane derivative 19 was also obtained from 9. Keywords: spiroannulation, geminal acylation, sesquiterpene synthesis.

Synthesis of bicyclo[4.1.0]hept-2-enes (trinorcarenes) by photochemical reaction of bicyclo[2.2.2]oct-5-en-2-ones

Photochemical reaction of bicyclo[2.2.2[oct-5-en-2-ones has been investigated as a prelude to focused application to the synthesis of sesquiterpenes such as sesquicarene and sirenin. Diels–Alder reaction of cyclohexa-2,4-dienes, having different substituents (methylthiomethyl and methoxy) at the C-6 position, with a dienophile proceeds regio- and stereo-selectively to give bicyclo[2.2.2]oct-5-en-2-ones; their photolysis in benzene upon high-pressure Hg lamp irradiation affords decarbonylation products, bicyclo[4.1.0]hept-2-enes (trinorcarenes), stereoselectively. Replacement of the methylthiomethyl group with a 2-ethoxycarbonylvinyl group improves the sequential reaction.

Formal substitution at both bridgeheads of a bicyclo[2.2.2]oct-5-en-2-one and its application to a synthesis of (±)-modhephene

Synthesis of a propellane sesquiterpene (±)-modhephene ( 23) was achieved on the basic of a novel procedure to introduce the desired alkyl groups at both bridgeheads of a bicyclo[2.2.2]oct-5-en-2-one.

Bryophyte Constituents; 6: Synthesis of Herbertene-Derived Sesquiterpenes from Herberta adunca

Efficient total syntheses are described for the racemic sesquiterpenes herbertenolide (2), α-herbertenol (3) and β-herbertenol (4) from Herberta adunca. ent-Herbertenolide [(+)-2] was prepared from enantiopure (-)-ethyl (1R)-1-methyl-2-oxocyclopentanecarboxylate (9) obtained from ethyl 2-oxocyclopentanecarboxylate (19) via reduction with baker’s yeast.

Total Synthesis of the Tricyclic Sesquiterpene (+/-)-Ceratopicanol. An Illustration of the Holosynthon Concept.

Total Synthesis of the Tricyclic Sesquiterpene (+/-)-Ceratopicanol. An Illustration of the Holosynthon Concept.

Production of volatile sesquiterpenes by Fusarium sambucinum strains with different abilities to synthesize trichothecenes.

Twenty-five strains of Fusarium sambucinum grown on wheat kernels were examined for trichothecene production and the synthesis of volatile sesquiterpenes. The volatiles were purged with air and collected on Tenax traps. Adsorbed compounds were eluted from the traps and injected into a gas chromatograph coupled with a mass spectrometer. Ten strains isolated from potato tubers produced high amounts of diacetoxyscirpenol and its derivatives. These strains were characterized by the production of high amounts of diverse sesquiterpenes. In 10 cultures, 19 compounds were detected, of which 6 were predominant and composed as much as 82% of the volatile sesquiterpene fraction (e.g., beta-farnesene, beta-chamigrene, beta-bisabolene, alpha-farnesene, trichodiene, and an unidentified compound). Fifteen strains isolated from various sources that did not produce trichothecenes produced much less volatile sesquiterpenes, with less chemical diversity. No more than six compounds were present in cultures. Two of these compounds were present in the toxigenic strains isolated from potatoes (beta-farnesene and acoradiene), but four were unique to the strains not producing trichothecenes (longifolene, isocaryophyllene, delta-elemene, and an unidentified one). The pattern of volatile sesquiterpenes was characteristic and distinctive for both toxic and nontoxic strains.

ChemInform Abstract: Synthesis of Phenolic Sesquiterpenes via Oxidative Cleavage of Benzocycloalkenols.

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Synthesis based on cyclohexadienes. Part 17. Total synthesis of the sesquiterpenes of Eremophila georgei diels

The first stereoselective total synthesis of the novel sesquiterpenes 1 and 2 is described. The preparation of the key intermediate 27 involved a rearrangement of a bicyclo[3.2.1]octane framework to an isomeric bicyclo[3.2.1]octene skeleton via a bicyclo[2.2.2]octane derivative.

Photocycloaddition-cyclobutane rearrangement to spiro cyclopentanones: application in a formal synthesis of (±)-α-cedrene

A novel four-step sequence has been developed for the construction of cyclopentanone at the carbonyl carbon of cyclic ketones 5 leading to the synthesis of functionalised spiro[4.n] systems 9. The key steps involve a pinacol-type rearrangement of ethoxycyclobutane derivatives 8 obtained from copper(I)-catalysed photocycloaddition of the dienes 7 prepared from the cyclic ketones 5. The methodology also works well on cyclic ketones with an additional functional group. For example, the ketones 13 and 20 produce the spiro ketone 19 ideally suited for synthesis of the acorane sesquiterpenes. The synthetic potential of this protocol has been demonstrated by a formal synthesis of α-cedrene 3.

Synthesis of phenolic sesquiterpenes via oxidative cleavage of benzocycloalkenols

Phenolic sesquiterpenes including sesquichamaenol, 6-(2-hydroxy-4-methylphenyl)-2-methyl-3-heptanone, and curcuphenol methyl ether have been obtained from oxidative cleavage of bicyclic precursors by treatment with acidic hydrogen peroxide in a process which probably parallels a biogenetic step A ketone intermediate for curcudiol has also been acquired in the same manner.

A simple total synthesis of (±)-spirojatamol and (±)-erythrodiene via intramolecular 1,3-dipolar cycloaddition

An efficient synthesis of spirobicyclic sesquiterpenes, (±)-spirojatamol 1 and (±)-erythrodiene 2, using an intramolecular 1,3-dipolar cycloaddition as the pivotal step is described.

Synthesis of β ‐Cyperone via Fungal Hydroxylation of thujone‐derived tricyclic cyclopropanes

AbstractSynthesis of optically active sesquiterpenes with a eudesmane C‐skeleton from the chiral starting material thujone involves transformation of a tricyclic intermediate (1R,2R,4S)‐1,7‐dimethyl‐4‐(1‐methylethyl)tricyclo[4.4.0.02,4]dec‐6‐en‐8‐one (2) into the bicyclic compound β ‐cyperone (5). Hydroxylation of 2 at C(5) or C(11) permits subsequent opening of the cyclopropane ring and rearrangement to β ‐cyperone. In this publication, studies involving hydroxylation of 2 by fungal cultures are presented. The resultant products are useful intermediates in efficient synthesis of eudesmane sesquiterpenes. Of five fungi tested, Rhizopus oryzae ATCC 11145 proved most versatile. It hydroxylates at the exocyclic C(11) position in high yield (70%) and, to a lesser extent, at C(5) (5%). Enzymatic activity appears at the end of growth phase and at least 2.2 g of 2 per liter can be metabolized without significant loss of product yield. A second fungus, Cunninghamella echinulata ATCC 9244, proved most useful for hydroxylation of derivatives of 2 for the preparation of derivatives of β ‐cyperone, although product yields were low (2–20%), some derivatives were nonreactive, and hydroxylation at C(9) occurred. The relationship between precursor structure and enzyme affinity is discussed.

The Total Synthesis of cis‐7,8‐Dihydroxy‐11,12‐dehydrocalamenene by Regio‐ and Diastereo‐selective Alkylation of Chiral η6‐Arenetricarbonylchromium Complexes: An Unexpected Case of Nucleophilic Aromatic tele‐Substitution with Methoxide as a Leaving Group

With complete diastereoselectivity and no loss of absolute stereochemical information, the chiral synthetic building block 1 is converted into 2, an advanced intermediate in the total synthesis of the antiinfective sesquiterpene 3. The reactivity of arene-Cr(CO)3 complexes is crucial to the synthetic strategy. TMS = SiMe3.

Total synthesis of the novel sesquiterpenes of Eremophila georgei Diels

The first stereoselective total synthesis of the natural sesquiterpenes 4 and 5, having the tricyclo[6.2.1.01,5]undecane skeleton with a bridgehead methyl group, is reported via the intermediate 9, which was obtained by the acid catalysed rearrangement of the alcohols 7 and 8.

Organic Reactivity Control by Means of Neighboring Groups and Organometallics. A Personal Account

This review summarizes the main topics of our research and covers the period of the last 15 years. The prime interest is focused on various ways of controlling the regio- and stereoselectivity of selected organic reactions, in particular electrophilic additions, cleavage of cyclopropane rings, and allylic substitutions by means of neighboring groups and/or transition and non-transition metals. In the first part, the factors governing the course of electrophilic additions are assessed, culminating in the formulation of selection rules for the reactivity of cyclohexene systems, and in a concise synthesis of the natural cardioactive drug, strophanthidin. These studies also contribute to a better understanding of the mechanisms of electrophilic additions. The second part describes recent developments in the stereo- and regiocontrolled cleavage of cyclopropane rings by non-transition metals (Tl and Hg), and the reactivity and transmetalation (with Pd) of the primary products. This methodology has resulted in novel routes to unique polycyclic structures, and will have synthetic applications in the near future. Evidence for the stereospecific "corner" cleavage of the cyclopropane ring has been provided for the first time for Tl and later for Hg. The third part deals with transition metal-catalyzed allylic substitution. Evidence for a new "syn" mechanism for the formation of the intermediate (π-allyl)palladium complex has been provided, which runs counter to the generally accepted "anti" mechanism. A novel method for a Pd-catalyzed allylic oxidation has been developed and employed in the synthesis of natural sesquiterpenes. The increasing importance of transition and non-transition metals for synthetic organic chemistry is demonstrated by their unique reactivity in a number of the papers included in this review.

Recent developments in the synthesis of drimane and lactarane sesquiterpenes

Abstract

Total synthesis of drimane sesquiterpenes from S-(+)-carvone (part 5)

Conjugate addition of potassium cyanide to S-(+)-carvone followed by annulation with methyl vinyl ketone nitrile 4 in high yield. Methylation of 4, removal of the isopropenyl group and the introduction of C-12 via formylation then gave the unsaturated keto lactone 21 which is an excellent intermediate in the total synthesis of drimane sesquiterpenes. This was demonstrated with the total synthesis of 3β-acetoxydrimenin 24.

First total synthesis of (±)-myltayl-4(12)-ene and single-crystal X-ray structure of exo-12-normyltaylan-4-yl 4-nitrobenzoate

The total synthesis of the unusual sesquiterpene (±)-myltayl-4(12)-ene 3 starting from the readily available cyclogeraniol 5 and the single-crystal X-ray structure of the 4-nitrobenzoate 12 of the noralcohol 11 are described.

Total synthesis of (1S,4S)-7,8-dihydroxycalamenene via benzylic alkylation of η 6-arene-Cr(CO) 3 complexes

The enantioselective total synthesis of the antiinfective sesquiterpene (1S,4S)-7,8-dihydroxy-calamenene ( 4) is accomplished by a strategy which centrally utilizes the reactivity of arene-Cr(CO) 3 complexes. In a sequence involving two successive benzylic deprotonation/alkylation steps, the chiral complex 8 (> 99% e.e.) is converted completely regio- and diastereoselectively to 7 and further by decomplexation and ether cleavage to the target compound 4 in high overall yield and without loss of enantiomeric purity.

Chlorination and base-induced dehydrochlorination of (-)-3-isothujone

Thujone (11, a natural product which is readily available in vast quantities from the Western red cedar (Thuja plicata Don) leaf oil, has been shown to be an effective chiral synthon for the synthesis of various sesquiterpenes.2 However, despite considerable work carried out on various aspects of its chemistry,= the overall picture concerning ita basic chemistry remained rather fragmented.5 Except for studies in the 50's on the tribromination of (+)-3thujone (1 b),8 a later paper on ita formylation? and a recent paper on the stereochemistry and mechanism of formation of 'tribromothujone,8 there appears to be no reports on the chlorination of the naturally occuring mixture of thujones, consisting primarily of (-)-3-isothujone (la).4-59g