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The design and synthesis of monosubstituted and disubstituted azanaphthoquinone annelated pyrroles with anticancer activity are described. N-alkylation with various side chains at the pyrrole ring led to a series of monosubstituted products. For preparation of disubstituted isoindole derivatives, appropriately substituted tosyl methyl isocyanides were used. The biological activity of all the compounds was evaluated against a number of cancer cell lines.

A series of carbinols has been synthesized by attachment of different piperidinyl side chains to the quinone structure of azanaphthoquinone annelated pyrroles. The synthesized compounds were screened for their cytotoxic activities. Compared to previously published results, they exhibited only moderate activities, thus showing that the existence of the quinone moiety seems to be essential for anticancer activities of this group.

We report the synthesis of novel anticancer compounds based on bioreductive and DNA-alkylating properties. The strategy was to combine a benzoquinone annelated pyrrole with bioreductive properties with a set of DNA-alkylating functionalities, thus resulting in bifunctional anticancer compounds. The biological activity of all compounds was evaluated against a number of cancer cell lines. One of the compounds should be emphasized.

The synthesis of the title compound is described. Hydroxylation of the endocyclic double bond of 2-acetyl-3,3-dimethylnorborn-5-ene furnished a mixture of nojigiku alcohol and the title compound. A shorter route leads from 2,5-norbornadiene solely to the desired camphoraceous smelling new hydroxy derivative to which the name isonojigiku alcohol is assigned.

The syntheses of the title compounds are described. Epoxidation of the endocyclic norbornene double bond leads to a series of epoxy derivatives of this class of terpenic compounds, which on account of their biological decomposability might turn out to be valuable microbiocides. Cleavage of the epoxide bridge of 5,6-epoxy-camphene opens a new access to the fragrance compound 7-syn-hydroxy-camphene via a rearrangement.

The synthesis of the title compound is described. Starting with the α-alkylation ofhomo-norcamphor followed by aWittig reaction, aTebbe transformation, and aDIBAH ester-reduction as the most important reactions of a 5 step sequence, (Z)-homo-β-santalol was obtained, which exhibits the typical precious sandalwood odour. The moderate increase of the volume of the bulky group obviously does not alter the odour quality “sandalwood” of this new β-santalol analogue.

The synthesis of the title compounds is described. Guided by theoretical considerations and molecular modeling studies, the influence of the bulky group opposite to the osmophorically important primary hydroxyl function on the odour impression is determined. The organoleptic evaluation proved the predicted sandal like odour of the (Z)-isomer and its also predicted absence with (E)-isomer. A moderate increase of the volume of the bulky group shows no influence on the sandalwood odour of the new analogue.

From bicyclo[2.2.2]octan-2-one (1) the β-hydroxy ketones 2-13 were prepared by aldol reaction with various aldehydes. Dehydration of the ketols furnished the corresponding enones 14-22. The odour properties of these bicyclic, rigid hydroxy ketones as well as of the enones are described.

By means of a convergent synthesis strategy, the title substance (Z)-7-oxa-β-santalol (4) was prepared starting with the side chain synthon 5-iodo-2-methyl-2-pentenylmethoxyethoxymethyl ether (7) and the bicyclic synthon ethyl 3-methylene-7-oxabicyclo[2.2.1]hept-5-ene-2-carboxylate (5). The new santalol analogue 4 is odorless, although the steric requirements for the sandalwood odor are met. The reasons for this are discussed.

Guided by molecular modeling studies, the synthesis of the title compound is described. The organoleptic evaluation proved the predicted real sandal like odour of (Z)-dehydro-homo-β-santalol.

Es wird gezeigt, das der Ester7a mit dem bicyclischen [4.1.0] Gerust als Ausgangsverbindung fur die Herstellung zahlreicher Aroma- u. Geruchsstoffe eingesetzt werden kann. Es wurden in der Folge 22 Derivate -uberwiegend Ester-synthetisiert und deren Geruchscharakteristik beschrieben, wobei funf Derivate auf Grund ihres angenehmen Gesamteindrucks besonders hervorgehoben werden.

The ozonolysis ofendo-2-acetyl-3,3-dimethylbicyclo[2.2.1]hept-5-ene (endo-1) and itsexo-epimer (exo-1) is described. The reaction products, after reductive work up as well as after oxidative work up, are characterized. The first procedure furnished the corresponding cyclopentane derivatives in good yield, namely 1,1-dimethyl-2-(1-hydroxyethyl)-3,5-bis-hydroxymethyl cyclopentane (2) as a cristalline compound fromendo-1, the epimeric10 as an oil fromexo-1. The oxidative work up furnished in both cases via keto-enol-tautomerism the same acid, 4-acetyl-5,5-dimethyl-1,3-cyclopentane dicarboxylic acid, characterized as its methyl ester. Selective oxidation of the secondary hydroxyl group in2 lead to the novel, tricyclic, even acid stable ketal17, with very interesting olfactory properties.

The reactivity of (−)-ephedrine (2) and (+)-norpseudoephedrine (3) towards the amidacetals1 a/b has been studied. Both2 and3 were acetylated resp. formylated at first at the amino group. Nevertheless, derivatives of2 and3 possessing a trisubstituted amino group react with1 a in a [3.3] sigmatopic rearrangement toortho substituted dimethylcarbamoylmethyl derivatives. By subsequent reduction with lithiumaluminiumhydride the aromatic compounds8,13, and18 with two aminoethyl groups are easily available. In contrast to these results1 b did not furnish any rearrangement products.

In continuation of studying structure/odour relationships of odourous compounds, the tricyclic patchouli-system is degraded to bicyclic structures by cutting the C6-C7 bond (8 and9) or by omitting the methylene group of C11 (12). The olfactory properties are studied and described by using the key odour descriptors — woody, earthy, and camphoraceous.

The separation of a complex mixture of a fragrance material into its isomers is described. Instead of an odour of sandalwood the mixture exhibits mainly a mushroom odour but also the pure isomers show other organoleptic qualities. The structure of two isomers could be ascertained mainly by13C- and1H-NMR-measurements, for two isomers a structure proposal is given.

Recombinant Escherichia coli cells expressing eight Baeyer-Villiger monooxygenases of bacterial origin have been utilized to oxidize prochiral heterocyclic ketones containing a pyran ring system. Within the biotransformation, two stereogenic centers were introduced with high control of enantioselectivity. The chemoselectivity of the enzymatic reaction was found to be high in favor of the Baeyer-Villiger process when using substituted ketone precursors incorporating functional groups labile to oxidation. A significantly different behavior was observed for two groups of monooxygenases with respect to substrate acceptance, which is consistent with our previous classification into two enzyme clusters.

Some derivatives of 5,6-dihydro-2H-pyran-3-carboxaldehyde (7) and of its oxidation product 5,6-dihydro-2H-pyran-3-carboxylic acid (8) have been prepared. The aldehyde derivatives as well as the amides and esters of8 have been tested in an insecticidal/fungicidal/acaricidal screening programme. The methylester35 shows a distinct knock down effect against the fruit flyDrosophila melanogaster.

The bicyclo[2.2.1]- and [2.2.2]-systems are part of numerous biological active substances. Continuing our syntheses in the isocamphane series the homologous isocamphanes of mecamylamine (1 a) and of the fungicidal bicyclic compound2 were synthesized. Furthermore the syntheses ofE-homoisosantalene (15) andE,E-homoisosantalol (16) are described.

The diketone1 undergoes base induced ring opening to the δ-ketoacid2 a. Subsequent stereoselective reduction of the carbonyl-group affords the corresponding hydroxyacid4 a and condensation leads to the bicyclic lactone5 which can be reduced to the title compound6. Similar O-cage-compounds are known for antiviral activity. The olfactory properties of the compounds5 and6 are described.

Some esters of isocamphenilanic acid (4) have been prepared and tested for their fungicidal and insecticidal activity. Esters of various acids with isocamphanyl ethylalcohol (5) have also been synthesized and included in the fungicidal/acaricidal/insecticidal screening programme. All esters bear a geminal dimethyl group at C-3 of the bicyclus which is important because of its shielding effect.

To study the structure/odour relationships of β-santalol analogues two homologous β-santalol derivatives5 and6 were synthesized. The key steps thereby were the α-alkylation of the bicyclic starting ketones8 and14 accomplished by using more drastic conditions as usual. The odours of5 and6 are described in detail.

A diastereoselective strategy for the synthesis of γ-pyrons was developed, starting from the Mg diacetonedicarboxylate complex. Initial cyclization with suitable anhydrides or acid chlorides, followed by hydrolytic decarboxylation leads to 2,6-disubstituted pyrans. Elevated pressure hydrogenation using Pd/C affords the title compounds in high diastereoselectivity. Scope and limitations of the method are outlined on selected examples.

In this study several 2/H-3,4-dihydropyrane-derivatives, substituted with different unsaturated alkyl groups, have been synthesized. These compounds exhibit pleasant green, fruity and flowery fragrances. The syntheses start from 2H-3,4-dihydropyrane-2-carbaldehydes which are available by dimerisation of acroleine, meth-ylacroleine and ethylacroleine. It was shown that it is possible to induce dimerisation by ultrasonic irradiation. Subsequent Wittig and Horner-Emmons olefinations lead to the desired pyrane derivatives. The odorous character of these compounds is fully described and remarkable structure/odour relationships are discussed.

Numerous bicyclic oximes are synthesized and for the first time the influence not only of the bicyclic nucleus but also of the α-geminai dimethyl group on the odourous character studied. The pleasant cassis odour of camphenilonoxime seems remarkable.

In der folgenden Arbeit wird gezeigt, das Schiffsche Basen als interessante Aroma- und Geruchsstoffe fungieren konnen. Ausgehend vom leicht zuganglichenendo-Camphenilylamin wurde eine Anzahl Schiffscher Basen durch Reaktion mit aromatischen Al-dehyden hergestellt und deren Geruch charakterisiert. Besonders hervorzuheben sind die Geruchsqualitaten vonendo-3,3-Dimethylbicyclo[2.2.1]heptyl(4-methoxy)-benzaldimin,endo-3,3-Dimethylbicyclo[2.2.1]heptyl(2-nitro)benzaldimin undendo-3,3-Dimethylbicyclo[2.2.1]-heptyl(3-methoxy-4-hydroxy)benzaldimin.

Syntheses of the title compounds are described and their olfactive properties discussed. Bishomocamphenilone (2) has been prepared by a Diels-Alder reaction of acrylonitril and cycloheptadiene-1,3 via the bicyclonitril5 which upon geminal chlorination and alkaline oxidation furnished the bishomonorbornanone9 which then could be transformed into2 by twofold methylation.14 has been prepared by action ofMeLi upon2 and bishomocamphene by dehydration of14. Hydroboration of this olefine3 yielded the alcohol15, which could be oxidized to the corresponding aldehyde13 and bishomocamphenilanic acid (4). The configurations of all new compounds has been ascertained.

Syntheses of the title compound and of some of its derivatives are described. Homocamphenilanic acid could not be obtained by aDiels-Alder reaction of cyclohexadiene with an appropriate dienophile but is easily accessible via homocamphene by hydroboration of this homoterpene and subsequent oxidation of the reaction product.

Most vegetables contain different amounts of iso- and anteiso-fatty acids, α-methylated acids were detected too, but so far only in tomatoes. Vegetables contain a great variaty of hydroxylated acids, especially α-hydroxy acids. The detected iso- and anteiso-fatty acids and alcohols may be the source of similar branched chain acids identified earlier in rather high amounts in skin and hairs of man and animals. They might also be the source of branched aldehyde components in plasmologens.

The synthesis of racemic 4,11,11-trimethyltricyclo[5.3.1.05,8]undec-4-en-7-ol (4), a new analogue of norpatchoulenol is described. ByDiels-Alder reaction of 6,6-dimethylcyclohexadienone (3) with methylvinyl ketone followed by hydrogenation and epimerization thesyn-diketone7 was obtained which then has been subjected to aGrignard reaction with vinyl magnesium bromide. After protection of the hydroxyl group of the resulting ketol8 the ketoether9 could be cyclisized to4 by means of a lithium suspension in refluxingTHF.4 shows a weak, characteristic odour of patchouli.