Synthese des (±)-Lasiodiplodins

Synthesis of (±)-Lasiodiplodin The synthesis of the plant growth inhibitor (±)-lasiodiplodin (VII), a 12 membered lactone of a substituted resorcylic acid is described. Condensation of methyl acetoacetate and methyl 11-hydroxy-2-undecenoate followed by treatment of the product with benzyl alcohol lead to the benzyl ether II which was aromatized via the benzeneselenenyl derivative. Methylation of the phenolic hydroxyl in III and conversion of the primary alcohol in the side chain into the secondary alcohol provided the hydroxy ester IV. The corresponding hydroxy acid V was transformed into the S-(2-pyridyl) carbothioate which cyclized under the influence of silver ions to yield 68% of 4-benzyl-lasiodiplodin (VI). Removal of the benzyl group by catalytic hydrogenation gave (±)-lasiodiplodin (VII).     

Synthese des (±)-Oncinotins

(±)-Oncinotin ( 19 ) is synthesized through the crucial intermediates 11 and 15 . By comparison of the synthetic product with natural (?)-oncinotin, it is found that the latter contains an isomeric substance, represented by structure 20 .     

Synthese von (±) Seychellen

A four step synthesis of Seychellene ( 1 ) is described. Intramolecular Diels-Alder reaction of dienon 2 furnished the tricyclic ketones 3 and 4 in good yield. Hydrogenation of 3 gave 5 and 6 . The higher reactivity of 6 with methyllithium compared to 5 allowed the selective preparation of 8 , which, on subsequent acid-catalyzed rearrangment afforded Seychellen in 57,5% yield. In an analogues manner epi-Seychellene was synthetized via the intermediates 5 and 7 .     

Eine neue Synthese von (±)-Pyrenophorin

A new Synthesis of (±)-Pyrenophorin The synthesis of pyrenophorin (I), a 16-membered dilactone metabolite of plant pathogenic fungi is described. Reaction of the Grignard reagent II with the activated succinic acid ester III gave the methyl (t-butyl)dimethylsilyloxy-oxo-octanoate IV which was converted into the corresponding ethylene acetal. Dehydrogenation via the benzeneselenenyl derivative lead to pyrenophorinic acid V with protected functional groups. Selective removal of silyl group followed by saponification of the ester group provided the ethylene acetal-hydroxy acid VI suitable for the cyclodimerisation reaction. This was effected with azodicarbonic acid ester and triphenylphosphine at ?40° in a dilute toluene solution. The 16-membered dilactones VII with protected carbonyl groups were isolated in 24% yield. Silver-ion induced cyclodimerisation of the S-2-pyridyl carbothioate of VI gave much lower yields. Removal of the acetal groups lead to (±)-pyrenophorin (I) and meso-pyrenophorin in about equal amounts.     

Eine neue Synthese von (±)-Dihydrorecifeiolid

A New Synthesis of (±)-Dihydrorecifeiolide Ethyl 1-(2′-formylethyl)-2-oxocyclooctane-1-carboxylate ( 2 ) prepared by Michael reaction of ethyl 2-oxocyclooctane-1-carboxylate ( 1 ) was regioselectively methylated at the aldehyde group with (CH₃)₂Ti[OCH(CH₃)₂]₂ to give 3 (Scheme 1). The alcohol 3 was treated with Bu₄NF to give the deethoxycarbonylated product 4 which by distillation gave the bicyclic enol ether 5 . Oxidation (m-chloroperbenzoic acid) of 5 and reduction of the resulting oxolacton 6 yielded the title compound (±)-dihydrorecifeiolide ( 7 ) in an overall yield of nearly 50 %. Methylation of the aldehyde 2 with MeLi gave the ring-enlarged lacton 9 in poor yield (13 %). The deethoxycarbonylation reaction 3 → 4 was studied in more detail (Scheme 3).     

Synthese von (±)-Diplodialid B und A

Synthesis of (±)-Diplodialide B and A Two steroid hydroxylase inhibitors, diplodialide B (1) and A (2) have been synthesized in the following way: The lithium enolate 5 of S-t-butyl thioacetate (4) was added to (E)-7-(2′-tetrahydropyranoxy)-2-octen-1-al (8) and the newly formed 3-hydroxy group in the product 9 was protected as t-butyl-diphenyl silyl ether followed by selective hydrolysis of the tetrahydropyranyl ether to give 10. Treatment with AgNO₃/H₂O cleaved the S-t-butyl ester group in 10 to give the corresponding hydroxy carboxylic acid which was converted into the S-2-pyridyl thioester by treatment with di(2-pyridyl)disulfide and triphenyl phosphine and cyclized with AgClO₄ to give the (4E,3,9-trans)- and (4E,3,9-cis)-lactone 11 and 12 (R?t-Bu(C₆H₅)₂Si) in 67% yield. Chromatographic separation of 11 and 12 and cleavage of the t-butyl-diphenyl silyl ether with tetrabutyl ammonium fluoride yielded (±)-diplodialide B (1) with (4E,3,9-trans)-configuration and the (4E,3,9-cis)-isomer 12 (R?H). Both isomers could be oxidized to diplodialide A (2) with manganese dioxide. The synthesis described above has also been carried out via the intermediates 10 , 11 and 12 with R?COOCH₂CH₂Si(CH₃)₃.     

Modellversuche in der Histrionicotoxinreihe Synthese des (±)-cis-1-Azaspiro[5.5]undecan-8-ols

As a first step toward total synthesis of histrionicotoxin and its congeners, the preparation of (±)-cis-Azaspiro[5.5]undecan-8-ol ( 11 ) is described.     

Synthese der Spermidin-Alkaloide (±)-Inandenin-10-ol,Inandenin-10-on und (±)-Oncinotin

Syntheses of the Spermidine Alkaloids (±)-Inandenin-10-ol, Inandenin-10-one, and (±)-Oncinotine New syntheses of the title compounds using two-ring-enlargement reactions are described. Starting from the aldehyde 1 , the corresponding 4′-aza derivative 15 could be obtained by reductive amination with the appropriate and protected spermidine derivative 14 (Scheme 4). Enlargement of the carbocyclic ring in 15 by five members gave, after further transformations, the hydroxylactam 18 . Transamidation of 18 , the second ring-enlargement step, led to (±)-inandenin-10-ol (7;22.9% overall yield) and, after oxidation, to inandenin-10-one ( 8 ; 22.5%, overall yield). (±)-Oncinotine 6 was synthesized by two pathways (Scheme 6): protection of the terminal NH₂ group by treatment with the Nefkens reagent and replacement of the OH group by Cl gave 24 , which by thermal transamidation followed by direct ring closure led to the oncinotine derivative 26 . The same intermediate could be obtained in higher yield via 28 by oxidation and protection of 18 followed by transamidation and reductive ring closure. Treatment of 26 with hydrazine finally gave (±)-oncinotine 6 in 15.9% overall yield.     

Zur Synthese des 1-Guajacyl-propandiols-(1,3)

Zusammenfassung Einige Darstellungsweisen des 1-Guajacyl-propandiols-(1,3), ausgehend vom Benzylvanilloyl-essigester (VI), der durch verschiedene Hydrierungsschritte in obige Verbindung übergeführt wurde, werden beschrieben. Im Zusammenhang damit werden Resultate japanischer Autoren diskutiert.     

Synthese makrocyclischer Ketone durch Ringerweiterung; ein neuer Weg zu(±)-Muscon

Synthesis of Macrocyclic Ketones by Ring-Enlargement Reactions; a New Path to (±)-Muscone A new synthetic route to macrocyclic ketones is described. Starting from 2-nitrocycloalkanones, the ring-enlarged compounds of the type 4 and 5 were prepared in three steps. Reduction of the NO₂ group with Bu³SnH and azobisisobutyronitrile led in moderate yields to simple β-keto-esters which were quantitatively hydrolyzed and decarboxylated to the ketones of the type 8 and 9 . The interesting fragrances Exaltone® ( 8a ) and (±)-muscone ( 9a ) were prepared in this way in overall yields of 22 and 18%, respectively.     

Synthese von (±)-Muscopyridin über eine C-ZIP-Ringerweiterungsreaktion

Synthesis of (±)-Muscopyridine via C-ZIP Ring Enlargement Treatment of 4-(1-nitro-2-oxocyclododec-1-yl)butanal ( 1 ) and of its methyl derivative 5 with pentylamine in EtOH at room temperature gave the ring-enlarged aminomethylidene derivatives 6 and 7 , respectively (Scheme 1). After hydrolysis of the aminomethylidene group in 6 and 7 and deformylation followed by a reductive Nef-type reaction, the macrocyclic diketones 10 and 11 , respectively, were obtained. They were transformed by a modified Hantzsch procedure to the title compound (±)-muscopyridine ( 13 ) and normuscopyridine ( 12 ), respectively.     

Michael-Addition von Thiocarbonsäureestern Anwendung bei der Synthese von (±)-Jasminketolacton

Michael addition of carbothioates. Application to the synthesis of (±)-jasmine ketolactone It is shown that the lithium enolate of S-t-butyl thioacetate adds to 2-cyclopentenone in the β-position and that fluoride ions catalyze the 1, 4-addition of the trimethylsilyl enol ether of S-t-butyl thioacetate ( 5 ) to 2-cyclopentenone ( 4 ) to give 6 . These novel versions of the Michael addition have been applied to a synthesis of jasmonoid compounds. Cleavage of the trimethylsilyl enol ether in 6 with tetrabutylammonium fluoride produced the corresponding ketone enolate which could be trapped in situ by alkylation with 1-bromo-5-(2′-tetrahydropyranoxy)-2-pentyne ( 7 ) to form 8 . Removal of the alcohol protecting group in 8 , followed by partial hydrogenation of the triple bond over Lindlar palladium and mercury ion promoted hydrolysis of the carbothioate moiety in 9 , led to 5′-hydroxy jasmonic acid ( 10 , Scheme 3). 10 was converted into the S-(2-pyridyl) carbothioate and cyclized in dilute benzene solution under the influence of silver ion to give (±)-jasmine ketolactone ( 1 , Scheme 4), a component of the essential oil of Jasminum grandiflorum, in 72% yield. Similarly, methyljasmonate ( 2 , Scheme 2) was obtained from 6 by the reaction with 1-bromo-2-pentyne and tetrabutylammonium fluoride followed by methanolysis and partial hydrogenation of the triple bond.