A Total Synthesis of (±)-Trichodiene

Trichodiene (1), a sesquiterpene hydrocarbon, was isolated from the extract of mycelium of Trichothecium roseum. The structure of trichodiene (1) was elucidated by Nozoe and Machida in 1970 via degradation and spectroscopy.¹ Trichodiene (1) has been shown to be the biogenetic precursor of the trichothecane family of sesquiterpenoids as characterized by the cytotoxic fungal metabolite (-)-trichodermin (2).^2,3 The structure and absolute stereochemistry of (-)-trichodermin (2) were determined by X-ray diffraction and, therefore, the structure and absolute stereochemistry of trichodiene (1) are now firmly established.⁴ We wish to report a total synthesis of (±)-trichodiene (1) via previously reported lactone 3.^5,6     

Oxidation of Cyclic Hemiacetals into Diketones: Final Steps in the Conversion of a Triterpenoid Ring a into a Steroidal Enone by a New Short Route

As a part of our studies in the conversion of triterpenoids into steroids we have reported¹ that the Jones oxidation of some triterpenoid hemiacetals (1) gives acyloxy acids (2) instead of the desired 1,5-diketones (3). We now report² the shortest route yet for the reconstruction of a triterpenoid ring A ketone (4) into a steroidal enone (7) involving as key steps the exhaustive Baeyer-Villiger oxidation³ of triterpenoid ketones (4) into δ-lactones (5) and mild chromium(VI) oxidation of cyclic hemiacetals (1) into diketones (3).     

Identification of diastereomeric cyclobutyl dimers in a mixture by NMR

The product obtained in a reaction of 3-methyl-4-nitro-5-styrylisoxazole (1) has been shown to be a diastereomeric mixture of two cyclobutyl dimers by NMR. A combination of¹H,¹³C spectra including DEFT, ASIS, 2D COSY and nOe techniques has established that centrosymmetric cyclobutane (7) and the isomer (8) with plane of symmetry are in 2:1 proportion.     

Syntisis of 4-Demethoxy-7, 11-dideoxydaunomycinone

Our continued interest in the total synthesis of natural and unnatural antitumor anthracyclines¹ especially the aglycones such as daunomycinone (1)² and 4-demethoxydaunomycinone (2)³, 11-deoxydaunomycinone (3)⁴ and 4-demethoxy-11-deoxydaunomycinone (4)⁵ led us to probe methods of obtaining these products of absolute enantitomeric purity. Earlier it was demonstrated that the AB ring synthon 5 having a chiral centre on fusion with phthalic anhydride gave 4-demethoxy-7-deoxy-daunomycinone (6) with no loss of optical purity⁶ and the same was further transformed to 2 [7-(S)-9(S)].     

A Convenient Synthesis of 3-Methoxyphthalic Anhydride

Many antibiotics of the anthracycline family¹ possess structures for which 3-methoxyphthalic anhydride (1) would be a suitable synthon² in a total synthesis. A classic synthesis of (1) has employed 3-nitrophthalic acid³ but, in our hands, proceeded in low overall yield. Recent syntheses have utilized the Diels Alder reaction of dimethyl acetylenedicarboxylate (2) with 1-methoxy-1,3-cyclohexadiene,⁴ 1,4-diacetoxybutadiene,⁵ 2-acetoxyfuran,⁶ 2-methoxyfuran⁷ or furan⁸ to obtain 3-hydroxyphthalic acid or a derivative. We now wish to report a convenient Diels-Alder synthesis of (1) from 3-methoxy-2-pyrone (3).     

A Convenient Synthesis of (Z)-7-Nonadecen-Ll-One and (Z)-7-Eicosen-Ll-Cne -the Pheromones of Peach Fruit Moth

In 1977 Tamaki¹ et al have isolated and synthesized² (Z)-7-nonadecen-ll-one (la) and (Z)-7-eicosen-l1-one (1b) which are active components of the female sex pheromones of the peach fruit moth Carposina niponensis Walsingham, a major economic pest of apple, peach and other fruits of Japan. We report in this communication a practical, convenient and stereospecific route to 1a and 1b.     

A Stereoselective and Regioselective Total Synthesis of (π)-Trichodiene

Trichodiene (1), a sesquiterpene hydrocarbon, was isolated and characterized by Nozoe and Machida in 1970.¹ Trichodiene (1) has been shown to be the biogenetic precursor of the trichothecane family of sesquiterpenoids characterized by the cytotoxic fungal metabolite (–)-trichodermin (2).^2,3 We recently reported a total synthesis of (±)-trichodiene (1) via lactone 3.⁴ Now, we wish to report another stereoselective total synthesis of (±)-trichodiene (1) via lactone 3 which is highly regioselective.     

An Improved Total Synthesis of (±) - Podocarpic Acid by a Cyclialkylation Route

A number of total syntheses of (±) - podocarpic acid (i) have been described¹ King, King and Topliss² first identified one of the products from nonstereo-selective cyclization of (4) with polyphosphoric acid as (±)- ethyl-O-methylpodocarpate (2) and correlated that with the corresponding acid (3), prepared in an extremly poor yield (ca 0.4%)³ by Bhattacharyya³, and Haworth and Moore⁴ by cyclization of (5) with a mixture of sulfuric acid and acetic acid. More recently Mancini, Fringuelli and Taticchi⁵ prepared (3) (in 4.8% yield) by repeating Howorth¹ s cyclization of (4). In continuation of our studies on cyclialky-     

A novel acid-catalyzed rearrangement of n-aryl-n′-aryloxyureas to biphenyl derivatives. A [5,5]-rearrangement involving three heteroatoms.

In the presence of trifluoroacetic acid, N-phenyl-N′-phenoxyurea (1a) rearranges to N-(4′-hydroxy-2-biphenylyl)urea (2a) and N-carbamoyl-2-hydroxy-diphenylamine (3a). The rearrangement is an intramolecular reaction, and the transition state of the breakage of the N-O bond is deduced to be polarized in the form N^δ- --- O^δ+. The reaction is entirely new and constitutes a fundamental aromatic rearrangement.     

Aminohaloborane in Organic Synthesis. V.1 An Aldol-Type Condensation of Acetonitrile and Phenylacetonitrile with Benzaldehydes Using Secondary Aminodichloroborane

3-Phenyl-3-sec-aminopropionitriles (1) are not found in literature. We describe here a simple synthesis of 1 from acetonitriles (2) and benzaldehydes (3) using sec-aminodichloroboranes (4)² and triethylamine (5).     

Oxygenation of Trimethylsilylallenes Readily Obtainable from Organoboranes. Syntheses of 1-Trimethylsilyl-1-alkyn-3-ones and 1-Trimethylsilyl-1-alkyn-3-ols

Abstract

Recently we have reported that the reaction of sodium methoxide with ate-complexes (1) readily prepared from trimethyl-silylpropargyl phenyl ether and organoboranes gives trimethyl-silylallenes (2) selectively (eq. 1).¹ In an attempt to find a new synthetic application of such silylallenes (2), the oxidation of 2 was examined. Although the usual oxidants such as m-chloro-perbenzoic acid were found to be unsuitable for the oxidation of the silylallenes, it was discovered that 2 was autoxidized at room temperature to propargylic hydroperoxide (3) (eq. 2). For example, the acidified starch-iodine test² strongly suggested the presence of the organic hydroperoxide in the reaction mixture obtained from 1,2-heptadienyltrimethylsilane (2, R=Bu) and oxygen. The hydroperoxide (3, R=Bu) was isolated in a 40% yield by distillation, 45–48 [ddot]C/0.1 mmHg. In the infrared spectrum, the OH stretching frequency appears at 3430 cm^?1 and the C°C at 2180 cm,^?1     

Synthesis of Some Non-Conjugated Dienones in the Retro-α-Ionone Series1

In the course of a study on the photochemical and thermal behaviour of β,γ-δ,ε-dienones^1-4, (E)-retro-α-ionone (2a) and a series of methylated (3, 4) and desmethyl analogues (2b-2e) have been synthesized by a simple deconjugative isomerization of the corresponding conjugated dienones in strong alkaline solution. 3-Methyl- (3) and 3,3-dimethyl-retro-α-ionone (4) have been prepared by addition of methyl chloride to a strongly alkaline solution of β-ionone (1a).⁵     

Synthesis of γ-Lactone of 1R-CIS 2,2-Dimethyl-3-(2,2,2-tribromo-1-hydroxyethyl)cyclopropane Carboxylic Acid,A Key Intermediate for Deltamethrin,From (+)-3-Carene

1R-cis-2,2-Dimethyl-3-(2,2-dibromovinyl)cyclopropane carboxylic acid¹ (1), the acid moiety of the highly potent photostable pyrethroid deltamethrin (2) has been obtained either by a Wittig reaction on 1R-cis-caronaldehyde ester (3) employing 1, 1-dibromomethylenetriphenylphosphorane or from the bicyclic tribromo-lactone^2,3 (4) by reaction with zinc and acetic acid. Lactone (4) is thus an important intermediate in the deltamethrin synthesis.     

An Efficient Synthesis of α-Bromoacetals via a Combined Chemical and Electrochemical Bromination

α-Bromoacetals (1) are valuable precursors in synthesis of α,β-unsaturated carbonyl compounds (2), 1-alkoxybutadienes² (3), ketene acetals³ (4), 2-methoxyallyl bromides⁴ (5) and other compounds. Because of our interest in the chemistry^5,6 of 3 and 4 we attempted to improve known procedures for the preparation of 1 with the aim to get a short and efficient synthesis of these compounds.     

(S)-(−)-2-Methyl-2-Phenylsuccinic Anhydride,a Novel Resolving Reagent and its Application to Resolution of CIS-5-Amino-4-Phenyl-1,3-DIOXANE

Abstract

A new resolving reagent, (S)-(?)-2-methyl-2-phenylsuccinic anhydride (5) for the resolution of amines via covalent bond formation and its application to the resolution of aminodioxane (±)-(1) is described. The d.e. of the amides (7) and (8) has been determined by studying ¹H-NMR spectra.     

New synthesis of ( E )-3,7-dimethyl-2,7-octadienylpropionate and ( E )-3,7-dimethyl-2-octen-1,8-diol, pheromone components of San Jose scaleinsect Quadraspidiotus pernicious and african monarch butterfly Danaus chrysippus

6-Methyl-6-hepten-2-one (3) on reaction with ethyl α-dimethylphosphonate/NaH gives a mixture of (E)-and (Z)-conjugated esters. The major (E)-isomer, (E)-ethyl-3,7-dimethyl-2,7-octadienoate (4), on reduction with LiAlH₄ at room temperature furnishes (E)-3,7-dimethyl-2,7-octadien-l-ol (5) which on propionylation affords (E)-3,7-dimethyl-2,7-octadienyl propionate (1). Carbinol (5) is converted into its silyl ether (E)-2,6-dimethyl-8-t-butyldimethylsilyloxy-l,6-octadiene (6) witht-Bu(Me)₂SiCl in CH₂Cl₂, which on hydroboronation-oxidation with 9-BBN/NaOH-H₂O₂ followed by disilylalion with (n-Bu)₄N⁺ F⁻ at room temperature, gives (E)-3,7-dimethyl-2-octen-l,8-diol (2).     

The Reaction of Diethanolamine with 2-Chloronitrobenzene-A Reinvestigation

In a report on the reaction of 2-chloronitrobenzene (1) with diethanolamine (2), Meltsner et al ¹ claim that the expected S_NAr product, N-(2-nitrophenyl)diethanolamine (3), is not formed; rather that the products are 2,2′-dichloroazobenzene (4), 2-nitrophenol (5), 2-chloroaniline (6) and 4-(2-aminophenyl)morpholine (7). Similar products in which the nitro function is reduced are also reported² for the corresponding reaction with ethanolamine. In this laboratory, in an attempted preparation of 2,2′-dichloroazobenzene (4) for reference purposes in photochemical studies on the antineoplastic agent 5-(3-azido-4-chlorophenyl)-6-ethyl-pyrimidin-2,4-diamine³, the expected S_NAr product (3) was obtained along with other products.     

Nebenreaktionen bei der radikalischen,intramolekularen Cycloaddition von 2.6-Bis(2-methacryloyloxy-5-methylbenzyl)-4-methylphenylmethacrylat. Beitrag zu einer Matrizenreaktion

Zusammenfassung Die mit 2-Cyano-2-propylradikalen aus AIBN ausgel?ste und beendete intramolekulare Cycloaddition von 2,6-Bis(2-methacryloyloxy-5-methylbenzyl)-4-methylphenylmethacrylat (1) gibt die Cycloaddukte 4-Methyl-1,2,6-benzoltriyl-2,6-bis(4-methyl-2-methy-len-1,2-phenylen)-2,9-dicyano-2,3,5,7,9-pentamethyl-3, 5,7-dekantricarboxylat (1a) und -2,9-dicyano-2,3,5,8,9-pentamethyl-3,5,8-dekantricarboxylat (1b), welche molekulareinheitliche Leiteroligpmere vorstellen. Daneben bildeten sich 10-(2-Cyano-2-methylpropyl)8-(2-cyano-2-propyl)-4- {2-[(2-cyano-2-methylpropyl) acryloyloxy]-5-methylbenzyl∼-2,8,10,15-tetramethyl-7, 11-dioxo-dibenzo[b,e]-1,7-dioxacyclododekan-2,5-dien (1c) und 6 {2-[4-Cyano-2-(2-cyano-2-propyl)-2,4-dimethylvaleryloxy]-5-methylbenzyl}-4,4′-dimethyl-2,2′-methylendiphenyl-bis[2-(2-cyano-2-methylpropyl) acrylat] (1d). Bezogen auf den Ausgangsester1 konnten insgesamt 92% getrennte und dünnschicht-chromatographisch reine Reaktionsprodukte gefa?t werden. Die den Verbindungen zugeordneten Strukturen wurden mittels IR- und UV-Spektren sowie¹H-NMR- und massenspektrometrische Analyse gesichert. Die Cycloaddukte1a und1b sind Produkte einer synthetischen Matrizenreaktion(7), deren Ergebnisse an anderer Stelle mitgeteilt werden soll.

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Summary The intramolecular cycloaddition of 2,6-bis(2-methacryloyloxy-5-methylbenzyl)-4-methylphenyl-methacrylate (1) was started and terminated by 2-cyano-2-propyl radicals from azoisobutyronitrile. The cycloadducts are 4-methyl-1,2,6-benzoltriyl-2,6-bis (4-methyl-2-methylene-1,2-phenylene)-2,9-dicyano-2,3, 5,7,9-pentamethyl-3,5,7-decanetricarboxylate (1a) and-2,9-dicyano-2,3,5,8,9-pentamethyl-3,5,8-decanetricarboxylate (1b), which are also molecularly uniform ladder oligomers. The side products are e]-1,7-dioxacyclododecane-2,5-diene (1c) and 6{2-[4-cyano-2-(2-cyano-2-propyl)-2,4-dimethylvaleryloxy]-5-methylbenzyl∼-4,4′-dimethyl-2,2′-methylenediphenyl-bis[2-(2-cyano-2 methylpropyl)acrylate] (1d). All together and relative to the starting ester1 92 % thin layer chromatographically pure reaction products could be isolated. The suggested structures of the compounds were confirmed by infrared and ultraviolet spectra as well as by¹H-NMR and mass spectroscopical analysis. The cycloadducts1a and1b are compounds of a matrix reaction (7). Their results will be published elsewhere.

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Mit 3 Abbildungen und 5 Tabellen     

Preparation of [18F]fluoromisonidazole by nucleophilic substitution on THP-protected precursor: Yield dependence on reaction parameters

The dependence of the radiochemical yield of [¹⁸F]fluoromisonidazole (1) on different reaction parameters such as reaction time, temperature and amount of precursor was investigated for the nucleophilic substitution of tosylate by [¹⁸F]fluoride and subsequent hydrolysis of the protecting group on 1-(2′-nitro-1′-imidazolyl)-2-O-tetrahydropyranyl-3-O-toluenesulfonylpropanediol as the precursor molecule (2). Highest yields (86%±6%) were obtained using 10 mg (2) at 100°C for 10 minutes, whereas both at 80 and 120°C the yields were lower (46%±11% and 29%±14%, respectively). A rapid decrease of the yield was observed when the reaction time exceeded 15 minutes, i.e., at 100°C using 5 mg (2) the radiochemical yield decreased from 61%±8% at 15 minutes to 18%±10% at 60 minutes.