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).     

Isolierung,Konstitution und Synthese der (R)-(−)-Eucominsäure

From the bulbs of Eucomis punctata L'Hérit. (Liliaceae) and of a hitherto undefined species of Eucomis a new optically active phenolic carboxylic acid, eucomic acid, was isolated. Structure 1 was assigned on the basis of chemical and spectral evidence. The absolute configuration of eucomic acid was determined by its correlation with piscidic acid ((2 R, 3 S)-2-(4′-hydroxybenzyl)-tartaric acid) ( 8 ). Consequently, eucomic acid is (R)-(?)-2-(4′-hydroxybenzyl)-malic acid ( 1 ). For the stereospecific synthesis, methyl cis-p-methoxybenzylidene-succinic acid ( 22 ) was transformed into the γ-lactone 24 which, by catalytic hydrogenolysis, yielded (±)-2-(4′-hydroxybenzyl)-malic acid 1-methyl ester ( 27 ). Resolution with (?)-quinine led to the enantiomeric acids 29 and 30 . The methyl ester of the levorotatory enantiomer 30 was identical with the dimethyl ester 3 of 4′-O-methyl-eucomic acid.     

Synthèse énantiospécifique du (−)-(1R, 3R, 5S)-diméthyl-1,3-dioxa-2,9-bicyclo[3.3.1]nonane

Enantiospecific Synthesis of (?)-(1R, 3R, 5S)-1,3-Dimethyl-2,9-dioxabicyclo[3.3.1]nonane The isomer (?)-(1R, 3R, 5S)-endo-1,3-dimethyl-2,9-dioxabicyclo[3.3.1]nonane ((1R, 3R, 5S)- 8 ) has been synthesized from (?)-(3R)-methyl 3-hydroxybutanoate. The key intermediate (3R, 5R)- 5 is proved to be a useful synthon for EPC syntheses.     

Synthesis of (R)- and (R)-4-methyl-6-2′-methylprop-1′-enyl-5,6-dihydro-2H-pyran (Nerol oxide) and Natural Occurrence of its Racemate

Following a known procedure, a mixture of (?)-(2S,3R)- and (+)-(2R,3R)-2,3-epoxy-citronellols ( 5 ) was prepared from (?)-(R)-linalool ( 3 ) via epoxy alcohol 4 and then reduced to (?)-(R)-3-hydroxy-citronellol ( 6 ). Sensitized photooxygenation of (?)-(R)-diol 6 led in part to (?)-(R)-triol 8 which was cyclodehydrated by dilute acid to a mixture of diastereoisomeric tetrahydropyran-4-ols 9 and 10 . Dehydration of hydroxy ethers 9 and 10 afforded (?)-(S)-nerol oxide ( 11 ) and (+)-(R)-nerol oxide ( 12 ), respectively, with an optical purity of 91%. Nerol oxide isolated from Bulgarian rose oil (0.038%) proved to be racemic. These results shed some light on the formation of nerol oxide in plants.     

2-(Trimethylsilyl)äthylester als Carboxylschutzgruppe; Anwendung bei der Synthese des (−)-(S)-Curvularins

2-(Trimethylsilyl)ethyl Esters as Carboxyl Protecting Group; Application in the Synthesis of (?)-(S)-Curvularin The mould metabolite curvularin (VIII) has been synthesized with the help of a new carboxyl protecting group that can be removed selectively with fluoride ions. 2-(Trimethylsilyl)ethyl 7-hydroxy-octanoate (III) was acylated with 3,5-dibenzyloxy-phenacetyl chloride (IV) to form V with two different ester groups. Tetrabutyl-ammonium fluoride in tetrahydrofuran cleaved the 2-(trimethylsilyl)ethyl ester in V selectively to form the carboxylate anion of VI together with ethylene and trimethylsilyl fluoride. Curvularin dibenzyl ether (VII) was formed by intramolecular acylation of VI. Removal of the benzyl ether groups in VII by hydrogenolysis led to (±)-curvularin (VIII). The naturally occurring (?)-enantiomer was formed when (+)-(S)-III served as starting material.     

Instructions to Authors (1994)

(1S,2R,6R,7R)-4-Phenyl-3,10-dioxa-5-azatricyclo[5.2.1.0^2,6]dec-4-en-9-one ((+)- 5 ) obtained in 6 steps from the Diels-Alder adduct of furan to 1-cyanovinyl (1S)-camphanate ((+)- 3 ) was reduced to the corresponding endo-alcohol (?)- 6 the treatment of which with HBr/AcOH provided (?)-(3aS,4S,6R,7S,7aR)-4β-bromo-3aβ,4,5,6,7,7aβ-hexahydro-2-phenyl-1,3-benzoxazole-6β,7α-diyl diacetate ((?)- 17 ). Elimination of HBr with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and acidic hydrolysis furnished (?)-(1R,2S,3R,4R)-4-aminocyclohex-5-ene-1,2,3-triol ( ? (?)-conduramine C₁;(?)- 1 ).     

Sarcodictyin A and Sarcodictyin B,Novel Diterpenoidic Alcohols Esterified by (E)-N(1)-Methylurocanic Acid. Isolation from the Mediterranean Stolonifer Sarcodictyon roseum

The Mediterranean stolonifer Sarcodictyon roseum (= Rolandia rosea) (Cnidaria, Anthozoa, Alcyonaria, Stolonifera, Clavulariidae) is shown to contain two novel diterpenoidic alcohols esterified by (E)-N(1)-methyl-urocanic acid (= E)-3-(l-methyl-lH-imidazol-4-yl)acrylic acid). They are sarcodictyin A ( = (?)-(4R,4a,R, 7R,10S,11S,12aR,lZ,5E,8Z)-7,10-epoxy-3,4,4a,7,10,11,12,12a-octahydro-7-hydroxy-6-(methoxycarbonyl)-1,10-dimethyl-4-(1-methylethyl)benzocyclodecen-11-yl (E)-3-(1-methyl-lH-imidazol-4-yl)acrylate; (?)- 1 ) and sarco-dictyin B (the 6-(ethoxycarbonyl analogue; (?)- 2 ). The assignment of the structures is mainly based on 1D- and 2D-NMR data, as well as on chemical transformations of (?)- 1 , such as transesterification with MeONa/MeOH giving methyl (E)-N(1)-methylurocanate ( 3 ) and the free alcohol (+)- 4 and reduction with LiAlH₄ followed by benzoylation giving dibenzoate 7. Absolute configurations are based on Horeau's method of esterification of (+)- 4 .     

Stereoselektive Synthesen von substituierten Tricarbonyl[tris(methylen)methan]eisen(0)-Komplexen

Stereoselective Syntheses of Substituted Tricarbonyl[tris(methylen)methan]iron(0) Complexes The complexes 3 , 9 , 10 , 22 , and 23 with one, two, and three Me substituents at the tris(methylen)methane moiety have been synthesized from the (acyloxy-1,3-diene)(tricarbonyl)iron(0) complexes 1 , 4 , 5 , 20 , and 21 , respectively, by ionic hydrogenation with BF₃ and Et₃SiH at ?78° in CH₂C1₂. These reductions are completely stereoselective, and their course can be predicted by assuming a dominant stereoelectronic control of the reaction. Formation of the carbocationic intermediates 11 from 4 and 12 from 5 , e.g., takes place only if the dissociating O? C bond is antiperiplanar to the donor C(β)? Fe bond. Fast H-transfer then converts the intermediate 11 to 9 and 12 to 10 . The configurations of 17 and 20 can be deduced from the structure of 22 and those of 18 and 21 from that of 23 . An X-ray structure determination of (1R,4S)camphanoate (?)- 13 derived from alcohol (?)- 7 confirms the configuration of 5 deduced above, The structures of the complexes 9 and 10 , 22 and 23 were determined by their unique NMR spectra. The diastereoisomeric complexes 6 and 7 have been synthesized from aldehyde 8 with MeMgI, the diastereoisomers 17 and 18 analogously from 16 or from methyl ketone 19 by reduction with LiAlH₄. Optically active starting materials (+)- 1 , (?)- 13 , (+)- 20 , and (+)- 21 gave, by ionic hydrogenation, the complexes (?)-(3R)- 3 , (+)-(2S,4S)- 10 , (?)-(R,R, S)- 22 , and (?)-(R,R,R)- 23 respectively, with known absolute configurations.     

Novel cembranolides (Coralloidolide D and E) and a 3,7-Cyclized cembranolide (Coralloidolide C) from the mediterranean coral Alcyonium coralloides

The Mediterranean alcyonacean Alcyonium (= Parerytkropodium) coralhides (PALLAS, 1766) is shown to contain three novel diterpenes which are of biogenetic significance: the 3,7-cyclized cembranoid Coralloidolide C ( = (+)-(6R*, 7R*, 11S*, 12aS* 3aE)-7,8-epoxy-3,5,6,7,8,9,10,11,12,12a-decahydro-12a-hydroxy-11-isopropenyl-1,4-dimethyl-3-oxocyciopentacydoundecene-8,6-carbolactone; (?)- 3 ), the O-bridged diketonic cembranolide Coralloidolide D (= (+)-(1R*, 2S*, 3R*, 5R*, 12S*, 8Z)-2,5-epoxy-1-hydroxy-12-isopropenyl-5,9-dimethyl-7,10-dioxocyclotetradeca-8-ene-1,3-carbolactone; (+)- 4 ), and the diketonic epoxycembranolide coralloidolide E (=(+)-(1R*, 2R*, 3R*, 12S*, 5Z, 8Z)-1,2-epoxy-12-isopropenyl-5,9-dimethyl-7,10-dioxocyclotetra-deca-5,8-diene-1,3-carbolactone; (+)- 5 ), The latter in pyridine at r. t. undergoes a double bond shift from C(4) = C(5) to C(4) = C(18) to give the isomer (?)- 7 . Structural assignments are mainly based on ID and 2D NMR and MS spectral data. Either corailoidolide A ((?)- 1 ) or the hypothetic unsaturated 1,4-diketone 9 can be envisaged as the precursors of all coralloidolides.     

(+)-(1S, 3S, 6S, 8S)-und (−)-(1R, 3R, 6R, 8R)-4, 9-Twistadien: Synthese und Bestimmung der absoluten Konfiguration

(+)-(1S, 3S, 6S, 8S)-and (?)-(1R, 3R, 6R, 8R)-4, 9-Twistadiene: Synthesis and Absolute Configuration A synthesis and the determination of the absolute configuration of (+)-(1S, 3S, 6S, 8S)- and (?)-(1R, 3R, 6R, 8R)-4, 9-twistadiene ((+)- and (?)- 4 , respectively) is described. Their chiroptical properties are compared with those of saturated twistane ((+)- and (?)- 5 ) as well as with those of the unsaturated and saturated 2, 7-dioxatwistane analogs (+)- and (?)- 9 , and (+)- and (?)- 10 , respectively, which also are compounds of known absolute configurations.     

Stereochemistry in Lewis acid-catalyzed silylation of alcohols, silanols, and methoxysilanes with optically active methyl(1-naphthyl)phenylsilane

Stereochemistry in silylation reactions of alcohols, silanols, and methoxysilanes with optically pure (R)-methyl(1-naphthyl)phenylsilane were studied in the presence of Lewis acid catalysts. Tris(pentafluorophenyl)borane [B(C₆F₅)₃] was found to be highly reactive and stereoselective in the reactions. Optically active (R)-(alkoxy)methyl(1-naphthyl)phenylsilanes with 91–97% ee were produced from alcohols through the inversion stereochemistry of the silane. Stereoselectivity in the reaction with triphenylsilanol was moderate (64% ee). (R)-1,3-Dimethyl-1-(1-naphthyl)-1,3,3-triphenyldisiloxane with 94% ee was obtained from the silane with (methoxy)methyldiphenylsilane. The reaction with (R)-(methoxy)methyl(1-naphthyl)phenylsilane (88% ee) gave (R, R)-1,3-dimethyl-1,3-di(1-naphthyl)-1,3-diphenyldisiloxane [(R, R):(R, S):(S, S) = 87:12:0.5]. The stereochemistry was proved to almost completely inversion and retention for the chiral silicon centers of the silane and methoxysilane, respectively.     

Synthesis and polymerization of (R)-(+)-2-methyl-2-ethyl-3-propiothiolactone

(R)-(+)-2-Methyl-2-ethyl-3-propiothiolactone was synthesized by debenzylation and cyclization of (?)-2-methyl-2-ethyl-3-benzylmercaptopropionyl chloride under the conditions of Friedel-Crafts synthesis, and by dehydration of (R)-(+)-2-methyl-2-ethyl-3-mercaptopropionic acid with dicyclohexyl carbodiimide. The configuration of the (+)-propiothiolactone was determined by chemical interconversion with (?)-2-methyl-2-ethylsuccinic acid, the absolute configuration of which is known to be (R). The polymerization of (R)-(+)-2-methyl-2-ethyl-3-propiothiolactone was performed in bulk with tetrabutylammonium versatate as catalyst. The specific rotation of the polymer ([α]_D +151.7°) compared with the rotation of the low molecular weight model compound (R)-(+)-2-methyl-2-ethyl-3-acetylmercapto-thiolpropionic acid methyl ester ([α]D +55.0°) shows a significant enhancement, thus suggesting the possibility of the presence of rigid conformations in polymer chain.     

Heterotricyclodecane XX (+)-(1S, 3S, 6S, 8S)- und (−)-(1R, 3R, 6R, 8R)-2, 7-Dioxa-twista-4,9-dien

(+)-(1S, 3S, 6S, 8S)- and (?)-(1R, 3R, 6R, 8R)-2,7-dioxa-twista-4,9-diene. A synthesis and the determination of the sense of chirality of (+)-(1S, 3S, 6S, 8S)- and (?)-(1R, 3R, 6R, 8R)-2,7-dioxa-twista-4,9-diene ((+)- 5 and (?)- 5 , respectively) is described.     

The mechamism of action of vitamin B12

A novel rearrangement reaction is introduced as a model for the rearrangement of methylitaconic acid (III) to α-methyleneglutaric acid (IV), one of three enzyme catalyzed, coenzyme B₁₂-dependent, carbonskeleton rearrangements whose mechanism has been a source of puzzlement for many years. The key feature of the new model is the direct attachment of the substrate, methylitaconic acid, to the cobalt atom of vitamin B₁₂ This was accomplished by reacting butadiene-2,3-decarboxylic acid with hydrobromic acid generating bromomethylitaconic acid (VIII). Use of two moles of hydrobromic acid yielded bis-2,3-(bromomethyl)succinic acid (IX). Reaction of the monobromide VIII with vitamin B_12s did not yield the desired carbon-cobalt bonded adduct. Instead, the lactone ηa- methylene-γbutyrolactone-β-carboxylic acid (X) was formed. Accordingly, the ester, dimethyl bromomethylitaconate (XIa), was reacted with vitamin B_12s and yielded the carbon-cobalt bonded adduct XIIa. Bis-trimethylsilyl bromomethylitaconate did not yield an adduct when reacted with vitamin B_12s, but bis-tetrahydropyranyl bromomethylitaconate (XIb) did yield the adduct XIIb. The ester cobalamin XIIb undergoes spontaneous decomposition at room temperature, in aqueous solution, at pH 8 and in the dark - biochemically ideal circumstances - yielding a mixture of butadiene-2,3-decarboxylic acid (VII), methylitaconic acid (III) and α- methyleneglutaric acid (IV). The presence of the latter indicates that a skeletal change has taken place in a way which mimics the enzymatic reaction. This is the first non-enzymic model in this carbon-skeleton rearrangement series. The methyl ester cobalamin XIIa was stable in the dark but did decompose on irradiation with a sunlamp to butadiene-2,3decarboxylic acid (VII) and methylitaconic acid (III). No α-methyleneglutaric acid IV was observed in the latter reaction.Authentic methylitaconic acid (III) was prepared by alkylation of triethyl prop-2-ene-l,l,2-tricarboxylate (XIII) with methyl iodide followed by hydrolysis and decarboxylation. The lactone X and lactone α-methyl-γ-butyrolactone-β-carboxylic acid (XVI) were prepared by condensing the triester XIII with formaldehyde, hydrolyzing the lactone diester XV to the lactone X and hydrogenating to the saturated lactone XVI.     

2, 3-Alkadiensäureester als Dienophile; Anwendung bei der Synthese von (+)-(R)-Lasiodiplodin

2,3-Alkadienoates as Dienophiles, Application in the Synthesis of (+)-(R)-Lasiodiplodin Methyl 2, 3-alkadienoates 2 are shown to react at 80° with l, 1-dimethoxy-3trimethylsilyloxy-l, 3-butadiene (1) to give the adducts 3 in good yields. Rearrangement of 3 , catalyzed by p-toluenesulfonic acid or by sodium methoxide, affords the 6-substituted methyl 4-hydroxy-2-methoxybenzoates 4 (R ? H, CH₃, C₆H₅). An analogous reaction sequence starting with (-)-(11 R)-dodeca-2, 3-dien-11-olide ((-) -6 ) and 1 leads, via the adduct (R)-7 , to (+)-( R )-lasiodiplodin ((+) ?8 ) with properties identical to those of the natural product. The allene lactone (-) -6 was prepared by an intramolecular Wittig condensation of (R) ?5 , produced from (–)-(R)-9-hydroxydecanoic acid.     

Stereospezifische Synthese von (+)-(3R, 4R)-4-Methyl-3-heptanol,das Enantiomere eines Pheromons des kleinen Ulmensplintkäfers (Scolytus multistriatus)

Stereospecific Synthesis of (+)-(3R, 4R)-4-Methyl-3-heptanol, the Enantiomer of a Pheromone of the Smaller European Elm Bark Beetle (Scolytus multistriatus) Reduction of 2 with actively fermenting baker's yeast gave (?) -3. Stereospecific alkylation [3] of (?) -3 with propyl iodide furnished ethyl (+)-(2R, 3R)-2-propyl-3-hydroxypentanoate ((+) -4 , 58%) which was converted to the tetrahydropyranyl ether (?) -5 , then the alcohol 6 , the p-toluenesulfonate 7 and the thiophenyl ether 8 to give the title compound (+) -1. The latter consisted of 97% of the threo- and 3% of the erythro-isomer. The above synthesis also correlates the absolute configuration of (?)-(R) -3 with that of (+)-(R)-citronellic acid (see [2]).     

Synthèse des (−)-(6R)-et(+)-(6S)-tétrahydro-6-[(Z)-pent-2-ényl]-2H-pyran-2-one,lactones de Jasminum grandiflorum L. et de Polianthes tuberosa L.

Synthesis of (?)-(6R)- and (+)-(6S)-Tetrahydro-6-[(Z)-pent-2-enyl]-2H-Pyran-2-one, lactones from Jasminum grandiflorum L. and from Polianthes tuberosa L. (?)-(2S)-Ethyl 2-hydroxyhexanedioate ((2S)- 2 ) was obtained by kinetic resolution of racemic ethyl 2-hydroxy-hexanedioate with baker's yeast. The key intermediates (+)-(5R)- and (?)-(5S)-ethyl 5,6-epoxyhexanoate ((5R)- and (5S)- 6 , resp.) are proved to be useful synthons for the total synthesis of chiral 6-alkyl-δ-lactones, as exemplified by the preparation of both enantiomers of jasmine lactone ((6R)- and (6S)- 10 , resp.).     

Alkaloids from Bulbocodium vernum L. Content material of Liliaceae-Wurmbaeoidaea

From whole plants of Bulbocodium vernum L. the flavone luteoline (I) and the alkaloids colchicine (II), N-formyl-N-deacetylcolchicine (III), 3-demethylcolchicine (V), (+)-bulbocodine (IX) and (?)-kreysigine (XI) were isolated in crystals. The presence of 2-demethylcolchicine (IV), ß- (VII) and γ-lumicolchicine (VIII), demecolcine (VI) and five not identified alkaloids was demonstrated by thin-layer chromatography. On the basis of ultraviolet, infrared and mass spectra, PMR.-analysis (Overhauser effect), and circular dichroism, the (6a-R, 8a-S)homo-proaporphine structure IX, with one methoxy group at C-2, has been assigned to (+)-bulbocodine. The (6a-R)-structure (XI) was deduced for (?)-kreysigine by comparing its optical rotation and circular dichroism which the values of (?)-multifloramine (X), the structure of which is known.     

Synthese von (−)-(R)-Nephthenol und (−)-(R)-Cembren A

Synthesis of (?)-(R)-Nephthenol and (?)-(R)-Cembren A Starting for L -serine,(?)-(R)-nephthenol((?)- 2 ) and (?)-(R)-cembren A((?)- 3 ) were synthesized.     

13C-NMR Spectra of 2- and 3-Phthalimido-3(2)-Benzimidazolylpropanoic Acid and 2- and 3-Phthalimidobenzimidazopyrrolone,Reaction Products of Phthaloylaspartic Anhydride with Ortho-Phenylenediamine

Two pairs of isomers of 3- and 2-phthalimido-3(2)benzimidazolylpropanoic acid (V and VI) and 2- and 3-phthalimidobenzimidazopyrrolone (VII and VIII) were produced from the reaction of phthaloylaspartic anhydride (I) with o-phenylenediamine (II). The ¹³C-NMR spectra of V and VI both showed 11 carbon signals indicating that the structures of their benzimidazole groups were symmetric. Isomers V and VI were easily distinguished from each other by the chemical-shift-differences (Δδ) of the methylene carbon and the methine carbon. Compounds VII and VIII displayed 14 carbon signals and no longer showed the symmetric structure of the benzimidazole moity, The chemical-shift-differences (Δδ) between methylene carbon and methine carbon in pyrrolones of VII and VIII can also be used to distinguish VII from VIII. The Δδ of compound VII is less than that of compound VIII.