B. J. M. Jansen

Insect antifeedant activity of clerodane diterpenes and related model compounds

A comprehensive compilation of all test results on the insect antifeedant activity of clerodane diterpenes and related model compounds is reported. To increase the compatibility of data from different sources, some of the results reported in the literature have been converted into a standardized form. The compounds were sorted into groups according to the different types of sidechain attached to C-9. Despite the wealth of information, collected in 15 tables, it remains difficult to assign importance to separate structural elements in relation to the observed antifeedant activity. A detailed analysis of the structure-activity relationships could not be presented, but some interesting trends can be distinguished based on the structures of the strongest antifeedants. The compilation covers the literature up to December 2001.

The synthesis of Ambrox®-like compounds starting from (+)-larixol

Abstract The oxidation of the (3-hydroxy-3-methyl-4-pentenyl)-side chain at C(9) of some labdanic diterpenoids with potassium permanganate was investigated. Triols, ketones, or cyclic enol ethers are the main reaction products, strongly influenced by the substituent at C(8). Further degradation of the methyl ketones by the Baeyer–Villiger reaction and modification of the exocyclic 8(17) double bond lead to suitable intermediates, which have been transformed into Ambrox®-like compounds. Synthetic routes using palladium catalyzed elimination or isomerization of allylic acetates, followed by ozonolysis have been developed as well for shortening of the side chain of (+)-larixol. Products from both routes have been cyclized to 6α-hydroxy Ambrox®. This compound was used as the key intermediate for the synthesis of several other Ambrox®-like compounds of which some showed pleasant odour properties.

The conversion of (-)- and (+)-dihydrocarvone into chiral intermediates for the synthesis of (-)-polygodial, (-)-warburganal and (-)-muzigadial.

Abstract (−)-Dihydrocarvone was converted into (−)-(4aR, 8aR)-3,4,4a,5,6,7,8,8a-octahydro-4a, 8,8-trimethylnaphthalene-2(H)-one (1) via an efficient route in which a Wolff-Kishner reduction, accompanied with a double bond isomerisation brought on a major simplification. Ketone 1 is a suitable intermediate for the syntheses of the insectantifeedants (−)-polygodial and (−)-warburganal. (+)-Dihydrocarvone was converted into (+)-(4aR, 7S, 8aR)-4a,7-dimethyl-8-methylene-3, 4,4a,5,6,7,8,8a-octahydronaphthalene-2(1H)-one (2), an intermediate ketone for the synthesis of (−)-muzigadial.

A novel synthesis of α-sulfenylated aldehydes

Abstract Ketones are converted into α-sulfenylated aldehydes with addition of one carbon atom via reaction with methoxyphenylthiomethyllithium followed by rearrangement of the adducts.

Lewis acid catalyzed Diels-Alder reactions of S-(+)-carvone1 with silyloxy dienes. Total synthesis of (+)-α-cyperone

Abstract The Diels-Alder reactions of S-(+)-carvone with 2-trimethylsilyloxy-1,3-butadiene, 3-trimethyl-silyloxy-1,3-pentadiene and 2-tert-butyldimethylsilyloxy-3-methyl-1,3-butadiene with ethylaluminium dichloride as catalyst are described. The synthetic value of the adducts is demonstrated by the total synthesis of (+)-α-cyperone from one of the adducts.

The synthesis of (-)-ambrox starting from labdanolic acid

Abstract Iododecarboxylation of labdanolic acid (1), followed by dehydrohalogenation led to alkenes 4 and 12. Both compounds were converted into (1R,2R,4aS,8aS)-1-(2-hydroxyethyl)-2,5,5,8a-tetramethyldecahydro-2-naphthalenol (8), which was transformed via cyclization into (−)-Ambrox® (9).

S-(+)-carvone as starting material in synthesis (part 4). Conjugate addition of cyanide and Grignard nucleophiles followed by annulation to functionalized decalones.

Abstract Two conjugate addition/annulation methodologies for S-(+)-carvone are reported. The conjugate addition of Grignard reagents, followed by the Lewis acid catalyzed Michael reaction of the intermediate silyl enol ethers with MVK and cyclization of the diketones, gave decalones 2a-d stereoselectively and in good yield. The conjugate addition of cyanide anion followed by base catalyzed Robinson annulation with MVK and dehydration gave decalone 2e stereoselectively in very high yield.

Total synthesis of (−)-Ambrox® from S-(+)-carvone (part 6)

Abstract Conjugate addition of cyanide and allyl nucleophiles to S-(+)-carvone followed by annulation with methyl vinyl ketone gave the substituted decalones 2 and 3 stereoselectively. Both decalones were transformed into (−)-Ambrox®via modification of the sidechain, methylation, conversion of the isopropenyl group and cyclization.

The synthesis of Ambrox®-like compounds starting from (+)-larixol. Part 2

Abstract Several Ambrox®-like compounds were synthesized in an enantiomerically pure form, and in relatively short procedures, starting from (+)-larixol. Triol 5 and enone 6 are important intermediates in these syntheses. The formation of Δ6-Ambrox®-type ethers was achieved by a new cyclization approach via ionization of the C(6)-allylic alcohol in ring B.

Enantioselective Synthesis of Functionalised Decalones by Robinson Annulation of Substituted Cyclohexanones, Derived from R-(−)-Carvone

Abstract The copper catalysed conjugate addition of methyl magnesium iodide to cyclohexenones and trapping of the enolate as its trimethylsilyl enol ether, followed by a trityl hexachloroantimonate (TrSbCl6) catalysed Mukaiyama-reaction, was applied to R-(−)-carvone. This proved to be an efficient method for the preparation of C-2, C-3 functionalised chiral cyclohexanones. These compounds were converted into their α-cyano ketones, which were submitted to Robinson annulation reactions with methyl vinyl ketone. The scope and limitations of these annulations were investigated. A series of highly functionalised chiral decalones were obtained that can be used as starting compounds in the total syntheses of enantiomerically pure clerodanes.