Investigations into the C‐deuteriation of silyl enol ethers derived from aryl alkyl ketones

Results are reported on the regioselective C‐deuteriation of a series of silyl enol ethers derived from aryl alkyl ketones using deuterium (D₂) gas as the deuterium source and palladium‐on‐barium sulfate as the mediator. These results highlight the numerous reaction pathways and different product types available from simple deuteriation of substituted enol precursors. Copyright © 2006 John Wiley & Sons, Ltd.     

Probing the regioselective C‐deuteriation of lithium enolates derived from 2‐methyl‐tetralone in the presence of substituted tertiary amines

Results are reported on the regioselective C‐deuteriation of 2‐methyl‐tetralone using a series of D‐sources and tertiary amines as potential mediators. The results presented further aid the understanding of kinetic deuteriation of both ‘base‐containing’ and ‘base‐free’ enolates. Copyright © 2006 John Wiley & Sons, Ltd.     

Investigations into the regioselective C‐deuteriation of enolates using a diisopropylammonium salt

Results are reported on the regioselective C‐deuteriation of 2‐methyl tetralone using a series of diisopropylamine derived D‐sources. The results presented further aid the understanding of kinetic deuteriation of both ‘base‐containing’ and ‘base‐free’ enolates. Copyright © 2002 John Wiley & Sons, Ltd.     

Investigations into the regioselective C‐deuteriation of enolates derived from 2‐methyl tetralone using piperidine‐d11

Results are reported on the regioselective C‐deuteriation of 2‐methyl tetralone using piperidine‐d₁₁ as a deuterium source. The results presented further aid the understanding of kinetic deuteriation of amine–enolate complexes. Copyright © 2004 John Wiley & Sons, Ltd.     

Investigations into the C‐deuteriation of aryl alkyl ketones using urea as a pro‐base in the presence of a deuterium donor

Results are reported on the regioselective C‐deuteriation of a series of enolates derived from the deprotonation of aryl alkyl ketones using dilithiated urea as the pro‐base in the presence of a suitable deuterium donor. Copyright © 2006 John Wiley & Sons, Ltd.     

Combining microwave‐enhanced deuteriation reactions with parallel synthesis procedures

The development of combined microwave‐enhanced/parallel synthesis procedures and their application to the deuteriation of organic compounds via examples of solid‐state hydrogenation is reported. Other labelling procedures, such as solution state catalytic dehalogenations, hydrogenations as well as hydrogen isotope exchange reactions also benefit from the combined technology. Copyright © 2003 John Wiley & Sons, Ltd.     

Acetylierende Ringöffnung von 3-substituierten 2.3-Epoxynitrilen

Ringopening of 3-Substituted 2,3-Epoxynitriles under Acetylating Conditions The reactivity of 2,3-epoxynitriles 1 towards various acetylating agents was studied. Depending on the reaction conditions, 2,3-diacetoxynitriles 2 , 2-acetoxy-3-chloronitriles 5 or enol acetates of α-ketonitriles 3 are formed as main products.     

雌三醇11位取代物的合成

为了寻找新的雌激素类药物,合成了(11),(14a)～(14d)等五个雌三醇的11位取代物(11α-OH,11β-OH,11α-OCH₃,11β-OCH₃,11β-OAc)供药理筛选。化合物的制备采用了新的合成路线;对△⁹⁽¹¹⁾-雌酚酮缩酮物(3)及11位取代雌酚酮烯醇酯化合物(10a),(10b)的硼氢化反应进行了考察,分离得到了9α-羟基物(5)及11位取代的16表雌三醇(13a)、(13b)等副产物。所有化合物的结构均通过光谱解析和化学转换得以确证。     

The synthesis and characterisation of deuteriated amides

Results are reported on the regioselective C‐deuteriation of a series of enolates derived from the addition of sec‐BuLi to a variety of substituted amides. The outcomes of the reactions are discussed in terms of the structural nature of the amides and the deuteriated sources employed. Copyright © 2003 John Wiley & Sons, Ltd.     

The synthesis and characterisation of multi‐labelled [D, 13C] 2‐deuterio‐2‐methyl aromatic ketones

A series of multi‐labelled aromatic ketones were efficiently synthesized using a deprotonation–deuteriation/alkylation strategy. The yields were high and the products are synthetically useful. Copyright © 2003 John Wiley & Sons, Ltd.     

Thieno[2,3‐d]pyrimidines in the Synthesis of Antitumor and Antioxidant Agents

Dimethyl acetylenedicarboxylate, ethyl propiolate, and E‐dibenzoylethylene react with thienopyrimidines (cyclo‐pentyl, ‐hexyl, and ‐heptyl) derivatives to form thiazolo[3,2‐a]thieno‐[2,3‐d]pyrimidin‐2‐ylidene) acetates, thieno[2,3‐d]pyrimidin‐2‐ylthioacrylates, and thieno[2′,3′:4,5]pyrimido[2,1‐b][1,3]thiazin‐6‐ones, respectively. Reactions proceed via cyclization and thio‐addition processes. Some derivatives of thienopyrimidines showed high inhibition of Hep‐G2 cell growth compared with the growth of untreated control cells. However, the fused heptyl of thienopyrimidothiazines indicates a promising specific antitumor agent against Hep‐G2 cells with IC₅₀ < 20 μM.     

Acetyl cedrene and its follower. An Isotopic,NMR and MS Structure elucidation and deuteriation study

Acetylation of cedarwood oil (Virginia) leads besides acetyl cedrene also to a minor product, 1,7,7‐trimethyl‐2,3‐(3′,4′‐dimethylbenzo)bicyclo[3.2.1]octane (follower). This product is identified by 2D NMR. Acetylation of cedarwood oil with ¹³C‐1 labeled acetic acid anhydride leads to a product labeled at the aromatic carbon C‐3′. From the ¹³C‐labeled compound ¹³C‐¹³C coupling constants could be measured. Acetyl cedrene is conveniently deuteriated by an acid‐catalysed exchange reaction using trifluoroacetic anhydride and D₂O. The product is found to be deuteriated both at the acetyl group and at the methyl group at the double bond (carbon 6). The reaction condition during deuteriation of cedrol leads to the elimination of the hydroxyl group at C‐6 with the formation of α ‐cedrene deuteriated at H‐5 and the methyl group at C‐6. Deuteriation of the follower leads to deuterium exchange at the aromatic carbons C‐5′ and C‐6′. Copyright © 2010 John Wiley & Sons, Ltd.     

三取代乙酸酯类化合物的合成

许多具有解痉作用的化合物亦有不同程度的镇痛作用。如早已在临床应用的杜冷丁,就是在合成哌啶类解痉剂中发现的,它既有解痉作用,又具镇痛作用。     

A new synthesis of [26,28‐2H6]brassinolide and [26,28‐2H6]castasterone via an unusual methyl migration

Deuterium‐labelled brassinosteroids, namely [26,28‐²H₆]castasterone, 8 , and [26,28‐²H₆]brassinolide, 9 , were synthesized starting from 6,6‐ ethylenedioxy‐20‐formyl‐2α,3α‐isopropylidenedioxy‐5α‐pregnane, 1 , and 3‐[²H₃]methyl‐but‐1‐yne‐[4,4,4‐²H₃], 11 . Upon alkylating cleavage of the epoxide 6 with trimethylaluminium‐n‐butyllithium an unusual migration of a neighbouring [²H₃]methyl group takes place to afford deuteriation at positions 26 and 28. Copyright © 2002 John Wiley & Sons, Ltd.     

Relationship of anesthetic activity of alkyl acetates to hydrophobicity and in vivo effect on membrane fluidity in mice

In vivo anesthetic activity of alkyl acetates in mice was studied in relation to hydrophobicity and the in vivo effect on membrane fluidity. The anesthetic potency (AD₅₀) of alkyl acetates was determined; AD₅₀ shows the i.p. dose required to anesthetize 50% of mice from the treated group. We used log P (n-octanol/water partition coefficient) as an operational definition of hydrophobicity. Membrane fluidity was determined using 1,6-diphenyl-1,3,5-hexatriene (DPH) as fluorescence probe. Log (1/AD₅₀) was a parabolic function of log P, and the value of log P that corresponds to the minimum AD₅₀ was estimated to be 2.08. Brain synaptosomal membranes were prepared from mice 30 min after dosing with each of the three alkyl acetates applied at 1.5-fold AD₅₀: n-butyl, n-amyl, and n-hexyl acetate. In each alkyl acetate group, most of the animals were anesthetized (>68%). Decreased membrane fluidity was observed for the animals that were anesthetized while no change in the fluidity was seen for the animals that were not anesthetized. The results suggest an involvement of decreased DPH fluidity in alkyl acetate-induced anesthesia. Received: 24 March 1997 / Accepted: 27 May 1997     

A gram‐scale synthesis of [3,4‐13C2,1α,7‐2H2]cortisone

A gram‐scale synthesis of [3,4‐¹³C₂,1α,7‐²H₂]cortisone from prednisone was developed. The deuterium atom at the C‐1 position was introduced through a regioselective and stereoselective deuteration of the 1,2‐double bond of the 1,4‐diene‐3‐one using Wilkinson's catalyst. After the oxidative cleavage of the A‐ring, two carbon‐13 atoms were introduced via acetylation of an A‐ring enol lactone with [1,2‐¹³C₂]acetyl chloride. The steroidal A‐ring was then reconstructed to incorporate the carbon‐13 atoms into the C‐3 and C‐4 positions. The deuterium atom at C‐7 was introduced through a regioselective deuteration of the 6,7‐double bond of a 4,6‐diene‐3‐one intermediate using palladium on strontium carbonate. The M + 4 stable isotope labeled cortisone was thus prepared in ca. 4% overall yield. In addition, [3,4‐¹³C₂,1α,7‐²H₂]‐11‐dehydrocorticosterone, [3,4‐¹³C₂,1α,7‐²H₂]cortisol, and [3,4‐¹³C₂,1α,7‐²H₂]corticosterone were also prepared. Copyright © 2011 John Wiley & Sons, Ltd.     

A quantitative gas-liquid chromatographic method for phorbol and related diterpenes as their acetates

A qualitative and quantitative gas-liquid chromatographic technique has been described for the acetates of the parent alcohols of several irritant and co-carcinogenic factors of the genera Croton and Euphorbia. Four columns have been found to be useful for the identification of the acetates of phorbol, 4-deoxy-4α-phorbol, 12-deoxy-phorbol, ingenol and crotophorbolone. A mixed SE-30, E.G.S. column was used for quantitative analysis using codeine as internal standard. Percentage standard errors of the estimated relative weight ratios of diterpenes to codeine varied from 0·9 to 1·27% for between 21 and 42 estimations. With plant latex samples the total recoveries of added ingenol were 98·3 ± 3%. The method has been used to evaluate the latex of E. lathyris, E. millii, E. desmondi, E. triangularis and E. tirucalli. The same samples were also assayed by an irritancy biological assay developed by Hecker.     

Detailed study of oxidative esterification and elimination reactions undergone by a steroidal 17 alpha-benzoyloxy-20-oxo-21-aldehyde

The reaction of 17 alpha-benzoyloxy-11 beta-hydroxy-3,20-dioxo-1, 4-pregnadien-21-al as the hemiacetal (1) with methanol:acetic acid:potassium cyanide:manganese dioxide followed by acetylation and preparative HPLC of the reaction mixture afforded 11 crystalline products. These products can be conveniently divided into three categories representing side-chain cleavage and oxidative esterification with or without elimination of the benzoyloxy group. Of special interest was the stereospecific formation of the C-17 cyanohydrin acetate 4a and the cis delta 17(20) enol acetate methyl ester 5. On the other hand, nonstereospecific addition of HCN to the side chain gave the C-20 epimeric cyanohydrin acetates 7a and 7b. The use of activated versus nonactivated MnO2 plays a major role in determining the quantitative distribution of the products. It was also discovered that even in the absence of MnO2, the reaction goes to completion. A proposed mechanism which explains the formation of all products is presented.     

Synthesis of [1‐11C]ethyl iodide from [11C]carbon monoxide and its application in alkylation reactions

A method is presented for preparing [1‐¹¹C]ethyl iodide from [¹¹C]carbon monoxide. The method utilizes methyl iodide and [¹¹C]carbon monoxide in a palladium‐mediated carbonylation reaction to form a mixture of [1‐¹¹C]acetic acid and [1‐¹¹C]methyl acetate. The acetates are reduced to [1‐¹¹C]ethanol and subsequently converted to [1‐¹¹C]ethyl iodide. The synthesis time was 20 min and the decay‐corrected radiochemical yield of [1‐¹¹C]ethyl iodide was 55 ± 5%. The position of the label was confirmed by ¹³C‐labelling and ¹³C‐NMR analysis. [1‐¹¹C]Ethyl iodide was used in two model reactions, an O‐alkylation and an N‐alkylation. Starting with approximately 2.5 GBq of [¹¹C]carbon monoxide, the isolated decay‐corrected radiochemical yields for the ester and the amine derivatives were 45 ± 0.5% and 25 ± 2%, respectively, based on [¹¹C]carbon monoxide. Starting with 10 GBq of [¹¹C]carbon monoxide, 0.55 GBq of the labelled ester was isolated within 40 min with a specific radioactivity of 36 GBq/µmol. Copyright © 2004 John Wiley & Sons, Ltd.     

中药赤芍中化学成分的研究

Two new monoterpene glycosides were isolated from the ethanolic extract of the root of Paeonia laetiflora Pall. The structure of compound (Ⅰ) has been identified as (Z)-(1S, 5R)-β-pinen-10-yl β-vicianoside; Compound (Ⅱ) is named lactiflorin and tentatively assigned as (Ⅱ).Compound (Ⅰ) is the glycoside of the enol form of an aldehyde. In compound (Ⅱ), the sugar moiety is attached to the aglycone by two ether-like linkages. Both seem to be unprecedented.