Stereoselective syntheses of 11-α-methoxycurvularin and 11-β-methoxycurvularin

A stereoselective synthesis of potent cytotoxic macrolides, 11-α-methoxycurvularin and 11-β-methoxycurvularin has been accomplished. The synthesis entailed Maruoka asymmetric allylation to introduce the stereocentres at C-11 and the key fragment was installed by using Grubbs cross-metathesis followed by CBS-reduction.     

Synthesis of 11C-labelled N,N'-diphenylurea and ethyl phenylcarbamate by a rhodium-promoted carbonylation via [11C]isocyanatobenzene using phenyl azide and [11C]carbon monoxide

The reaction with phenyl azide and [11C]carbon monoxide to give N,N'-diphenyl[11C]urea and ethyl phenyl[11C]carbamate has been studied with the aim of development of a new methodology for carbonylation using [11C]carbon monoxide with high specific radioactivity. The synthesis of 11C-labelled N,N'-diphenylurea from phenyl azide and [11C]carbon monoxide, with 1,2-bis(diphenylphosphino)ethane-bound Rh(I) complex at 120 degrees C at a pressure of 35 MPa in the presence of aniline was accomplished in 82% trapping efficiency and 82% conversion yield. This approach was also useful for the synthesis of ethyl phenyl[11C]carbamate with lithium ethoxide as a nucleophilic reagent giving 90% trapping efficiency and 76% conversion yield. These reactions can be considered to proceed via a [11C]isocyanate or a [11C]isocyanate-coordinated Rh complex to give the corresponding 11C-products. This protocol provides the chemical basis for the synthesis of [11C]urea and [11C]carbamate derived from [11C]isocyanates.     

Syntheses of 11-hydroxy and 11-hydroxy-11-methyl-14-methoxy-14-azadispiro[5.1.5.2]pentadec-9-ene-7,15-diones

A facile synthesis, which permits regioselective incorporation of hydroxy and/or methyl substituents at position 11 of 14-methoxy-14-azadispiro[5.1.5.2]pentadec-9-ene-7,15-dione, has been described.     

MgAPO-11分子筛的合成及Pt/MgAPO-11在正十二烷临氢异构化反应中的催化性能

 采用常规水热合成法合成了系列MgAPO-11分子筛,考察了晶化时间、 P/Al投料比和Mg源对MgAPO-11分子筛的物相、酸性以及Pt/MgAPO-11催化正十二烷临氢异构化反应性能的影响. 分别用X射线衍射、 X射线荧光光谱和NH3程序升温脱附测定了样品的晶相、 Mg含量和酸性质. 结果表明,合成条件影响着合成产物的晶相组成、 Mg含量及酸性质,从而影响到Pt/MgAPO-11在正十二烷临氢异构化反应中的催化性能. 反应结果显示, Pt/MgAPO-11催化剂的催化活性与MgAPO-11分子筛的强酸位数目密切相关. 较短的晶化时间、合成凝胶的P/Al摩尔比为1.0以及使用Mg(NO3)2为Mg源有利于提高MgAPO-11的强酸位数目,从而提高Pt/MgAPO-11的催化活性.     

Automated preparation of carbon-11 ethanol and carbon-11 butanol for human studies using positron emission tomography

An automated continuous flow process has been developed for the synthesis of¹¹C-ethanol and¹¹C-butanol. These alcohols were synthesized via the same route. The reaction of¹¹CO₂ with methylmagnesium bromide or with n-propylmagnesium chloride, followed by a lithium aluminum hydride reduction and hydrolysis produced respectively¹¹C-ethanol and¹¹C-butanol. Preparation can be completed in 25 min. In each case the radiochemical purity, as determined by high pressure liquid chromatography /HPLC/ was greater than 98%. Biological quality control shows that the products are suitable for human use. The process has been completely automated to limit radiation exposure to personnel, reduce preparation time, and increase reproducibility.     

Conversion of 11-keto-9-beta, 10-alpha-steroids on 10-alpha-compounds. Synthesis of 10-alpha-cortisone, 11-oxo-10-alpha-progesterone, 10-alpha-androsterone and analogs of 11-hydroxy-compounds

Isomerisation of 11-keto-9β, 10α(retro)-steroids by acid or base led to the thermo-dynamically more stable 11-keto-10α-isomers, which have not yet been described in the literature. This epimerisation at C-9 constitutes a new route for the synthesis of 10α-steroids. The steric factors responsible for this isomerisation are discussed.     

Synthesis of 11H-Pyrido[2,1-b]quinazolin-11-one and Derivatives

The synthesis of 11H-pyrido[2,1-b]quinazolin-11-one (IV) and derivatives, by the condensation of o-chlorobenzoic acid and 2-aminopyridine in DMF is reported.     

Automated synthesis system for production of 11C-glucose

A fully automated synthesis system of 11C-glucose by the photosynthesis method has been developed for clinical use. This system has been designed to be as convenient as possible for routine use, and the full automation of the whole procedure from the target gas recovery to collection of the final 11C-glucose/fructose mixture has been accomplished by microcomputer control. A mixture of 11C-glucose/fructose (1:1) was obtained with 20 approximately 35% of radiochemical yield within 60 min.     

Synthesis of 8α-acetoxydriman-11-oic acid

A five-stage synthesis of 8α-acetoxydriman-11-oic acid from the readily available bicyclohomofarnesane-8α,12-diol has been developed.     

Regiospecific,enantiospecific total synthesis of the alkoxy-substituted indole bases, 16-epi-N(a)-methylgardneral, 11-methoxyaffinisine,and 11-methoxymacroline as well as the indole alkaloids alstophylline and macralstonine

A regiospecific, enantiospecific approach to the synthesis of ring-A-substituted indole alkaloids was developed via a doubly convergent strategy. The asymmetric Pictet-Spengler reaction and enolate-driven palladium cross-coupling processes were both executed in stereospecific fashion and served as the stereochemical basis of this approach. The synthesis of 16-epi-N(a)-methylgardneral (15), 11-methoxyaffinisine (16), and 11-methoxymacroline (22) has been accomplished in high yield and in enantiospecific fashion. Moreover, the key C-19 ketosarpagine system (borane adducts) 19a,b employed for the construction of 11-methoxymacroline (22) was also transformed into alstophylline 25, which resulted in completion of the total synthesis of the bisindole macralstonine (1). [reaction: see text]     

Synthesis of 11beta-perfluorohexylestradiol

[reaction: see text] We report the synthesis of 11beta-perfluorohexylestradiol 1e using a perfluoroorganometallic reagent for the introduction of the fluorous part. This compound is useful for biological studies and for imaging the ERalpha estradiol receptor distribution in the whole cell by secondary ion mass spectrometry (SIMS). The key step of this synthesis involves the radical reduction of an 11beta-oxalate derivative. The stereochemical outcome of this reaction was studied for a range of C11 substituents, and we attempted to rationalize the apparent abnormal behavior of the phenyl group.     

Effect of the template on synthesis of SAPO-11 for hydroisomerization of n-octane

Summary In this study, five typical dialkylamines with different alkyl chains were tested as template for synthesis of SAPO-11. Among these templates, diethylamine, dipropylamine and diisopropylamine have been shown to be effective for synthesis of SAPO-11. SAPO-11 synthesized with dipropylamine in the gels of high Si content and diisopropylamine in the gels of low Si content exhibit good catalytic performance in hydroisomerization of n-octane.     

Enantiospecific synthesis and confirmation of the relative and absolute stereostructure of 11-hydroxyguaiadienes

Enantiospecific total synthesis of two epimeric sesquiterpenes 11-hydroxyguaiadienes has been accomplished starting from the readily available monoterpene (R)-limonene, which confirmed the structure and absolute configuration of the natural products.     

The synthesis of 11β-alkyl-19-norsteroids: a novel class of potent steroid hormones—I : The synthesis of 11β-methyl and 11β-ethylestradiol

The syntheses of 11β-methyl and 11β-ethylestradiol, via Grignard adducts to 11-oxoestra-1,3,5(10)-trienes, attempted modification of the Torgov total synthesis of steroids, and 11β-methylticogenin, are described.     

Asymmetric synthesis of L-2-amino[3-11C]butyric acid, L-[3-11C]norvaline and L-[3-11C]valine

The short-lived radionuclide 11C (t1/2 = 20.4 min) has been used in the asymmetric synthesis of L-2-amino[3-11C]butyric acid, L-[3-11C]-norvaline and L-[3-11C]valine. The syntheses were performed by alkylation of [(+)-2-hydroxypinanyl-3-idene]-glycine tert-butyl ester under anhydrous conditions in tetrahydrofuran/1,3-dimethyl-3,4,5,6-tetrahydro-2-pyrimidinone with lithiated 2,2,6,6-tetramethylpiperidine as base, using the appropriate 11C-alkyl iodides prepared in a one-pot reactor from [11C]carbon dioxide. Following removal of the protecting groups, the -[3-11C]amino acids were obtained in 80-82% enantiomeric excess and in 9-25% radiochemical yields, decay corrected and calculated on the basis of the amount of [11C]carbon dioxide at the start of the syntheses within 50-55 min.     

A Simple and Short Synthesis of Z-6-Heneicosen-11-One and Z-1,6-Heneicosen-11-One,The Sex Pheromones of Douglas-Fir Tussock Moth

Z-6-Heneicosen-11-one (1) and Z-1,6-Heneicosen-11-one (2) are the sex pheromones of the Douglas-Fir Tussock moth, ‘Orgyia Pseudo Sugata’, isolated^1,2 in 1975 and 1978 respectively. In contrast with other lepidopterous pheromones, which are unsaturated C₁₂-C₁₄ primary alcohols or acetates, these were found to be C₂₁ ketones. The Douglas-Fir Tussock moth is a severe defoliator of the Fir forest; consequently, considerable interest attends the synthesis of these two pheromones. A number of syntheses of these two pheromones have been reported3 amongst which is one of our synthesis using N,N-dimethyl acetone 4 hydrazone as key intermediate.     

Asymmetric total synthesis of 11-deoxytetrodotoxin,a naturally occurring congener

Tetrodotoxin, a toxic principle of puffer fish poisoning, is a specific blocker of sodium channel. Despite many synthetic efforts since the structure elucidation in 1964, the only total synthesis of the racemic tetrodotoxin has been reported by Kishi and co-workers. In the course of our studies directed toward the total synthesis to analyze biologically interesting issues associated with tetrodotoxin, we accomplished a highly stereocontrolled synthesis of (-)-5,11-dideoxytetrodotoxin in 1999. Based on the synthesis, we describe herein the first total synthesis of 11-deoxytetrodotoxin, a naturally occurring analogue. The synthesis started from an allylic alcohol, the same intermediate for the synthesis of 5,11-dideoxytetrodotoxin. Epoxidation of the allylic alcohol was followed by isomerization with Ti(i-PrO)(4) to give an alpha-hydroxy allylic alcohol, in which the configurations of the two hydroxyl groups were inverted by oxidation and then a 2-step reduction. Further epoxidation of the allylic alcohol and ozonolysis of the remaining vinyl group gave an aldehyde, which reacted with magnesium acetylide to give a propargyl alcohol in a stereoselective manner. Oxidative cleavage of the acetylenic moiety with RuO(4) afforded a fully functionalized lactone for 11-deoxytetrodotoxin. Crucial guanidinylation was achieved from trichloroacetamide according to our own method to give acetyldibenzylguanidine. Finally, deprotection of benzyl groups, acetates, and acetal furnished 11-deoxytetrodotoxin.     

Synthesis of 11C-amides using [11C]carbon monoxide and in situ activated amines by palladium-mediated carboxaminations

[11C]Carbon monoxide at low concentrations, aryl halides and amines were used in the palladium-mediated synthesis of twenty 11C-amides. In the study several approaches to improve the radiochemical yield were explored. Eight of the selected amides were prepared by in situ activation of the amines using lithium bis(trimethylsilyl)amide and the radiochemical yields of these reactions were improved compared to utilising a previous reported method. In the synthesis of 1-[carbonyl-11C]benzoyl-3-methyl-1H-indole (11) from 3-methyl-1H-indole (25), the corresponding organotin-amine was prepared prior to the acylation reaction. In a typical experiment, N-(4-hydroxyphenyl)[carbonyl-11C]acetamide (5) was prepared in 15% radiochemical yield using 4-aminophenol (20) but the yield increased to 63% when the amine was activated by lithium bis(trimethylsilyl)amide.     

The total synthesis of (+/-)-11-O-debenzoyltashironin

The total synthesis of the putative non-peptidyl neurotrophic factor 11-O-debenzoyltashironin has been accomplished. The key transformation involves a biomimetic oxidative dearomatization/transannular Diels-Alder sequence that closes the tetracyclic carbon skeleton present in the natural product.     

Establishing the absolute configuration of the asbestinins: enantioselective total synthesis of 11-acetoxy-4-deoxyasbestinin D

A highly stereoselective synthesis of 11-acetoxy-4-deoxyasbestinin D (1) has been completed in 26 linear steps. The synthesis hinges on a selective glycolate aldol addition to establish the C-2 stereocenter, a ring-closing metathesis reaction to complete the oxonene, and an intramolecular Diels-Alder cycloaddition to establish the relative configuration at C-1, C-10, and C-14. This initial total synthesis of an asbestinin also serves to confirm the absolute configuration of this subclass of the C-2-C-11-cyclized cembranoid natural products.