Investigation of the [1,5]-hydride shift as a route to nitro-Mannich cyclisations

Conditions were found for the [1,5]-hydride shift nitro-Mannich reaction that led to the synthesis of 2,3-disubstituted tetrahydroquinolines. Two simple cyclic amine substrates gave diastereomerically pure rearranged products in 65 and 90% yields by refluxing in HFIP. A more general procedure used Gd(OTf)3 as a catalyst and successfully rearranged other cyclic and acyclic amines in 42–84% yield with diastereomeric ratios of 75:25 to >95:5 in favour of the anti-diastereoisomer (9 examples). Two examples of sulphur containing heterocycles gave lower yields of 9 and 25%. Electron withdrawing substituents were shown to have a deleterious effect on the success of the reaction. The results indicated the limitation of the [1,5]-hydride shift nitro-Mannich reaction with respect to the stability of the intermediate iminium ion.     

An approach toward azacycles using photochemical and radical cyclizations of N-alkenyl substituted 5-thioxopyrrolidin-2-ones

The photochemical reactions of a series of cyclic N-alkenyl-substituted thioimides have been examined. Irradiation of N-3-methylbut-3-enyl-5-thioxo-pyrrolidin-2-one (16) results in intramolecular [2 + 2] cycloaddition to give the highly strained thietane 17, whose structure was confirmed on the basis of its X-ray analysis. Treatment of cycloadduct 17 with dimethyl(methylthio)sulfonium tetrafluoroborate gave 2,5,6,7-tetrahydropyrrolizin-3-one (20) in good yield. Further reduction of 20 with Raney-Ni afforded 5,5-dimethylhexahydro-pyrrolizin-1-one (21). This sequence of reactions demonstrates the facility with which the 2 + 2 photoadduct can be converted into the pyrrolizidine alkaloid core skeleton. The photochemistry of the closely related N-butenyl thioxopyrrolidin-one (22) proceeded in a slightly different fashion and produced 7-mercaptomethyl tetrahydropyrrolizin-3-one (24) in 68% yield. In contrast to the above results, irradiation of the thioxaphthalimido system containing an N-cycloalkenyl group in the side chain gave rise to products derived by gamma-hydrogen abstraction from the n-pi triplet excited state. The photobehavior of the related N-3-alkenyl pyrrolidine-2,5-dithione system (62) was also studied and found to give products derived from both a 2 + 2 cycloaddition (63) and hydrogen atom transfer (64). Finally, the reaction of several N-alkenyl substituted thioimides (71-73) with tributylstannane in the presence of AIBN gave cyclized products derived from transient radical intermediates.     

Synthesis of highly functionalized chiral nitriles by radical fragmentation of beta-hydroxy azides. Convenient transformation of aldononitriles into 1,4- and 1,5-iminoalditols

The synthesis of highly functionalized nitriles by an alkoxyl radical fragmentation of cyclic beta-hydroxy azides is described. The alkoxyl radicals were generated by reaction of the alcohols with (diacetoxyiodo)benzene and iodine under mild conditions compatible with the presence of sensitive substituents and the protective groups most frequently used in carbohydrate chemistry. To explore the scope and limitations of this methodology, experiments were carried out using a variety of beta-hydroxy azides of the carbohydrate (1-6, 33, and 41), monoterpenoid (21 and 22), and steroid (23-25) families of natural products. Of special interest are the aldopentonitriles (15-18, 34, and 42) and aldotetrononitriles (19 and 20) synthesized from the corresponding 2-azido-2-deoxycarbohydrates. To demonstrate the versatility of these aldononitriles as chiral synthons, 1,4-imino-1-deoxysugar (37) and 1,5-imino-1-deoxysugar (43) analogues of the polyhydroxypyrrolidine and -piperidine types were prepared.     

Stereoselective total synthesis of (±)-peribysin E

Radical cyclization of iodoketone 3 afforded cis-hydrindanone 8. Compound 8 was converted into key intermediate 5 via conventional transformations. Annulation of a spiro-lactal unit to 5 was pursued with three different approaches. In the first approach, radical cyclization of propargyl ester 17 provided spiro-lactone 18 with an undesired stereochemistry. Attempts to invert the stereochemistry at the spiro-center via retro-aldol and aldol condensation of compound 20 failed. In the second approach, key intermediate 5 was transformed into 23. Acylation of compound 23 gave 24 as a single diastereomer with the desired stereochemistry but in low yield. NBS bromination of 24 followed by lactone formation gave 26 in low yield. Alternatively, allylic oxidation of 24 with SeO(2) followed by lactonization gave 26 also in low yield. Finally, a third approach employing a semipinacol-type rearrangement of epoxy-alcohol 33 gave aldehyde 34 with the desired stereochemistry. Treatment of compound 34 with HCl in MeOH effected spiro-lactal formation and provided (±)-peribysin E. The overall yield of our synthesis is 3.2% from 2-methylcyclohenen-1-one.     

Enantiopure Aminopyrans by a Lewis Acid Promoted Rearrangement of 1,2‐Oxazines: Versatile Building Blocks for Oligosaccharide and Sugar Amino Acid Mimetics

1,3‐Dioxolanyl‐substituted 1,2‐oxazines, such as syn‐ 1 and anti‐ 1 , rearrange under Lewis acidic conditions to provide bicyclic products 2 – 5 . Subsequent reductive transformations afforded enantiopure 3‐aminopyran derivatives such as 7 and 9 or their protected diastereomers 16 and 18 , which can be regarded as carbohydrate mimetics. An alternative sequence of transformations including selective oxidation of the primary hydroxyl groups in 21 and 24 led to two protected β‐amino acid derivatives with carbohydrate‐like backbone (sugar amino acids). Treatment of bicyclic ester 23 with samarium diiodide cleaved the N? O bond and furnished the unusual β‐lactam 27 in excellent yield. Alternatively, γ‐amino acid derivative 29 was efficiently prepared in a few steps. Fairly simple transformations gave azides 32 and 35 or alkyne 30 which are suitable substrates for the construction of oligosaccharide mimetics such as 34 by copper iodide catalyzed cycloadditions. With this report we demonstrate that enantiopure rearrangement products 2 – 5 are protected precursors of a variety of polyfunctionalized pyran derivatives with great potential for chemical biology.     

Phase-transfer-catalyzed asymmetric acylimidazole alkylation

2-Acylimidazoles are alkylated under phase-transfer conditions with cinchonidinium catalysts at -40 degrees C with allyl and benzyl electrophiles in high yield with excellent enantioselectivity (79 to >99% ee). The acylimidazole substrates are made in three steps from bromoacetic acid via the N-acylmorpholine adduct. The catalyst is made in high purity allowing for S-product formation (6-20 h) under mild conditions, consistent with an ion-pair mechanism. The products are readily converted to useful ester products using methyltriflate and sodium methoxide, via a dimethylacylimidazolium intermediate without racemization. The process is efficient, direct, and amenable to other electrophiles and transformations that proceed through an enolate intermediate.     

Rearrangement of 2-quinolyl- and 1-isoquinolylcarbenes to naphthylnitrenes

2-quinolylcarbene 23 and 1-isoquinolylcarbene 33 are generated by flash vacuum thermolysis (FVT) of the corresponding triazolo[1,5-a]quinoline and triazolo[5,1-a]isoquinoline 19 and 29, as well as 2-(5-tetrazolyl)quinoline and 1-(5-tetrazolyl)isoquinoline 20 and 30, respectively. These carbenes rearrange to 1- and 2-naphthylnitrene 21 and 31, respectively, and the nitrenes are also generated by FVT of 1- and 2-naphthyl azides 18 and 28. The products of FVT of both the nitrene and carbene precursors are the 2- and 3-cyanoindenes 26 and 27 together with the nitrene dimers, viz. azonaphthalenes 25 and 35, and the H-abstraction products, aminonaphthalenes 24 and 34. All the azide, triazole, and tetrazole precursors yield 3-cyanoindene 26 as the principal ring contraction product under conditions of low FVT temperature (340-400 degrees C) and high pressure (1 Torr N(2) as carrier gas for the purpose of collisional deactivation). This ring contraction reaction is strongly subject to chemical activation, which caused extensive isomerization of 3-cyanoindene to 2-cyanoindene under conditions of low pressure (10(-3) Torr). 2-Cyanoindene is calculated to be ca. 1.7 kcal/mol below 3-cyanoindene in energy; accordingly, high-temperature FVT of these cyanoindenes always gives mixtures of the two compounds with the 2-cyano isomer dominating. Photolysis of trizolo[1,5-a]quinoline 19 and triazolo[5,1-a]isoquinoline 29 in Ar matrixes causes partial ring opening to the corresponding 2-diazomethylquinoline 19' and 1-diazomethylisoquinoline 29'. The photolysis of the former gives rise to a small amount of the cyclic ketenimine 22, the intermediate connecting 2-quinolylcarbene and 1-naphthylnitrene.     

Further studies on synthesis of the 12,13-seco norditerpenoid alkaloids

After a series of optimization for the reaction conditions (reagents, reaction temperature, etc.), treatment of the sulfonates 4, 8, 13 and 15 with 8% NaOH (room temperature, 24 h) via a semipinacol rearrangement afforded the corresponding C-nor compounds 5, 9, 12 and 16, as the major of a pair of epimer at C-16, to an excellent extent, in 95%, 92%, 100% and 90% yield, respectively. The 12,13-seco compounds 21 and 22 (23) were obtained in 20% and 60% yield, respectively, by treating 5 with Br(2)-glacial HOAc (room temperature, 24 h). Treatment of the C-nor compounds 5 or 6, 16 or 17, and 28 from 10 with SOCl(2)-anhydrous benzene (room temperature, overnight) afforded the 12,13-seco compounds 24, 26 and 30 in 70% or 100%, 40% and 66% yield, respectively. When treatment of the C-nor compound 29 from 9 under same conditions gave the 12,13-seco products 30, 31 and 32 in 33%, 26% and 20% yield. When treating 21 or 24, and 26 with 5% KOH in EtOH afforded the 12,13-seco compounds 25 and 27 quantitatively, respectively. The compound 31 converted to 30 quantitatively by treatment with Na(2)CO(3) in MeOH. All of the new compounds were isolated and fully characterized.     

Catalytic enantioselective Reissert-type reaction: development and application to the synthesis of a potent NMDA receptor antagonist (-)-L-689,560 using a solid-supported catalyst.

Full details of the first catalytic enantioselective Reissert-type reaction are described. Utilizing the Lewis acid-Lewis base bifunctional catalyst 5 or 6 (9 mol %), the Reissert products were obtained in 57 to 99% yield with 54 to 96% ee. Electron-rich quinolines produced better yields and enantioselectivities than electron-deficient substrates. Kinetic studies indicated that the reaction should proceed via the rate-determining acyl quinolinium formation, followed by the attack of a cyanide. The catalyst does not facilitate the first rate-determining step; however, it strongly facilitates the second cyanation step. The reaction was successfully applied to an efficient catalytic asymmetric synthesis of a potent NMDA receptor antagonist (-)-L-689,560. A key step is the one-pot process using the Reissert-type reaction from quinoline 1f, followed by stereoselective reduction of the resulting enamine 2f. This step gave the key intermediate 20 in 91% yield with 93% ee, using 1 mol % of 6. The enantiomerically pure target compound was obtained through 10 operations (including recrystallization) in total yield of 47%. Furthermore, 6 was immobilized to JandaJEL, and the resulting solid-supported catalyst 11 afforded 20 in a comparable yield to the homogeneous 6, but with slightly lower enantioselectivity.     

A convenient synthesis of 2′-deoxy-6-thioguanosine,ara-guanine,ara-6-thioguanine and certain related purine nucleosides by the stereospecific sodium salt glycosylation procedure

A simple and high-yield synthesis of biologically significant 2′-deoxy-6-thioguanosine ( 11 ), ara-6-thioguanine ( 16 ) and araG ( 17 ) has been accomplished employing the Stereospecific sodium salt glycosylation method. Glycosylation of the sodium salt of 6-chloro- and 2-amino-6-chloropurine ( 1 and 2 , respectively) with 1-chloro-2-deoxy-3,5-di-O-(p-toluoyl)-α-D-erythro-pentofuranose ( 3 ) gave the corresponding N-9 substituted nucleosides as major products with the β-anomeric configuration ( 4 and 5 , respectively) along with a minor amount of the N-7 positional isomers ( 6 and 7 ). Treatment of 4 with hydrogen sulfide in methanol containing sodium methoxide gave 2′-deoxy-6-thioinosine ( 10 ) in 93% yield. Similarly, 5 was transformed into 2′-deoxy-6-thioguanosine (β-TGdR, 11 ) in 71 % yield. Reaction of the sodium salt of 2 with 1-chloro-2,3,5-tri-O-benzyl-α-D-arabinofuranose ( 8 ) gave N-7 and N-9 glycosylated products 13 and 9 , respectively. Debenzylation of 9 with boron trichloride at ?78° gave the versatile intermediate 2-amino-6-chloro-9-β-D-arabinofuranosyl-purine ( 14 ) in 62% yield. Direct treatment of 14 with sodium hydrosulfide furnished ara-6-thioguanine ( 16 ). Alkaline hydrolysis of 14 readily gave 9-β-D-arabinofuranosylguanine (araG, 17 ), which on subsequent phosphorylation with phosphorus oxychloride in trimethyl phosphate afforded araG 5′-monophosphate ( 18 ).     

Ring Closing Metathesis Using Chiral Template Consisting of Hard and Soft Parts

Summary: Macrocyclic compounds having 18-, 19-, 22-, and 23-membered rings were prepared quantitatively by ring closing metathesis of diene substrates consisting of a rigid o- or m-phthalate group and flexible but geometrically regulated 2,4-pentanediol tethers. From the p-phthalate analogues, the ring closing metathesis and the cyclic dimmer formation were observed to give 24-membered ring (70% yield) and 40-membered ring (65% yield) respectively.     

Enantioselective total synthesis of (-)-triptolide, (-)-triptonide, (+)-triptophenolide, and (+)-triptoquinonide

The first enantioselective total synthesis of (-)-triptolide (1), (-)-triptonide (2), (+)-triptophenolide (3), and (+)-triptoquinonide (4) was completed. The key step involves lanthanide triflate-catalyzed oxidative radical cyclization of (+)-8-phenylmenthyl ester 30 mediated by Mn(OAc)3, providing intermediate 31 with good chemical yield (77%) and excellent diastereoselectivity (dr 38:1). (+)-Triptophenolide methyl ether (5) was then prepared in > 99% enantiomeric excess (> 99% ee), and readily converted to natural products 1-4. In addition, transition state models were proposed to explain the opposite chiral induction observed in the oxidative radical cyclization reactions of chiral beta-keto esters 17 (without an alpha-substituent) and 17a (with an alpha-chloro substituent).     

Intramolecular Pauson-Khand reactions of methylenecyclopropane and bicyclopropylidene derivatives as an approach to spiro(cyclopropanebicyclo[n.3.0]alkenones)

The trimethylsilyl-protected enynes 9a-c and 14a,b with alkynyl substituents on the three-membered ring or on the double bond of a methylenecyclopropane or a bicyclopropylidene moiety were prepared in two steps from the alcohols 6a-c and 12a,b, respectively, by conversion to the iodides and their coupling with lithium (trimethylsilyl)acetylide (8) in 38-73% overall yields. The bicyclopropylidene derivative 9d was synthesized in 49% yield directly from bicyclopropylidene (3) by lithiation followed by coupling with (5-iodopent-1-ynyl)trimethylsilane (11). Enynes 9b-d were protiodesilylated by treatment with K2CO3 in methanol to give the corresponding unprotected enynes 10b-d in 53, 74 and 94% yield, respectively. Enynes 17a-c with a carbonyl group adjacent to the acetylenic moiety were synthesized from oxo derivatives 15a-c by Wittig olefination followed by coupling with 8 in 47, 18 and 12% overall yield, respectively. Pauson-Khand reactions of the methylenecyclopropane derivatives with a substituent on the ring (9a,b and 10a) as well as on the double bond (14a,b and their in situ prepared protiodesilylated analogues) proceeded smoothly by stirring of the corresponding enyne with [Co2(CO)8] in dichloromethane at ambient temperature followed by treatment of the formed complexes with trimethylamine N-oxide under an oxygen atmosphere at -78 degrees C to give tricyclic or spirocyclopropanated bicyclic enones 18a,b, 19a, 20a,b, 21a,b in good yields. Alkynylbicyclopropylidene derivatives 9c,d and 10c,d formed the corresponding cobalt complexes at -78 to -20 degrees C. Treatment of the latter with N-methylmorpholine N-oxide under an argon atmosphere at -20 degrees C gave the spirocyclopropanated tricyclic enones 18c, 19c and 18d in 31-45% yields. The structure of 19c was proved by X-ray crystal structure analysis. The cyclization of enynones 17a-c in MeCN at 80 degrees C gave the spirocyclopropanated bicyclic diketones 22a-c in 38-65% yields. Intramolecular PKRs of the enynes 25a,d with a chiral auxiliary adjacent to the triple bond gave the corresponding products 26a,d in 70 and 79% yield, respectively, as 5:1 and 8:1 mixtures of diastereomers, respectively. Addition of lithium dimethylcuprate or higher order cuprates to the double bond of the former furnished bridgehead-substituted bicyclo[3.3.0]octanones 27a-c in 57-86% yields. Protiodesilylation of 27a followed by acetal cleavage gave the enantiomerically pure spirocyclopropanated bicyclo[3.3.0]octanedione (1R,5R)- 29a with [alpha]D(20)=-148 (c=1.0 in CHCl3) in 55% overall yield.     

A kinetic study of the reactions of the hydrogen atom with the cyclohexadiene isomers in the gas phase

Absolute values of the rate constants for the reaction of hydrogen atoms with cyclic olefins in the gas phase have been measured in a discharge-flow system under 3.5, 16, and 22 torr Ar at 23°C. The attenuation of hydrogen atom concentration in the reaction tube in the presence of a large excess of olefin was measured with an ESR spectrometer, and the products were analyzed by gas chromatography. Cyclic C₆ hydrocarbons were the only significant products obtained when the hydrogen atom concentration was 2.6 × 10^?10 mole/1., the olefin concentration was in the range of 9 to 22 × 10^?8 mole/1., and the pressure was 16 torr Ar. The values for the rate constants for reaction with cyclohexadiene-1,3, cyclohexadiene-1,4, and cyclohexene are, respectively, (9 ± 2) × 10⁸, (12 ± 1) × 10⁸, and (6 ± 1) × 10⁸ l./mole-sec, and they are not changed significantly by a sixfold change in total pressure. The fraction of the total interaction that proceeds by addition is 84% in the cyclohexadiene-1,3 system, but only 18% in the cyclohexadiene-1,4 system, and the cyclohexadienyl radical is therefore the dominant radical species in the latter system. The pattern of interaction between the hydrogen atom and the cyclohexadienyl radical was determined, and comprises 65% of disproportionation, and 13% and 23% of combination to yield cyclohexadiene-1,3 and cyclohexadiene-1,4, respectively. These results are consistent with the general patterns of reactivity emerging from studies of the reactions between free radicals and olefins in related systems.     

Stereoselective hydrostannation of substituted alkynes with trineophyltin hydride

Hydrostannation of mono- and disubstituted alkynes with trineophyltin hydride (1) leads to vinylstannanes in good to excellent yields, the configuration of the products depending on the reaction conditions. Thus, whereas hydrostannation under radical conditions leads stereoselectively to only one of the two possible products corresponding to an anti addition in 60–99% yield, the additions catalyzed by bis(triphenylphosphine)palladium dichloride gave mixtures of the syn adducts (60–79% yield). Full ¹H-, ¹³C-, and ¹¹⁹Sn-NMR as well as mass spectra data of the organotin adducts are given.     

2-quinoxalinylnitrenes and 4-quinazolinylnitrenes: rearrangement to cyclic and acyclic carbodiimides and ring-opening to nitrile ylides

This work was undertaken with the aim to obtain direct evidence for the interrelationships between hetarylnitrenes, their ring-expanded cyclic carbodiimide isomers, and ring-opened nitrile ylides. Tetrazolo[1,5-a]quinoxaline 11T and tetrazolo[5.1-c]quinazoline 13T undergo valence tautomerization to the corresponding azides 11A and 13A on mild flash vacuum thermolysis (FVT). Photolysis in Ar matrixes at ca. 15 K affords the triplet nitrenes 12 and 14, identified by ESR, UV, and IR spectroscopy. The nitrenes are converted photochemically to the seven-membered ring carbodiimide 15 followed by the open-chain carbodiimide 22. The 3-methoxy- and 3-chloro-2-quinoxalinylnitrenes 24 yield the ring-expanded carbodiimides 26 very cleanly on matrix photolysis, whereas FVT affords N-cyanobenzimidazoles 28. The ring-opened nitrile ylides 36 and 49 are identified as intermediates in the photolyses of 2-phenyl-4-quinazolinylnitrene 32 and 7-nitro-2-phenyl-4- quinazolinylnitrene 47. In these systems, a photochemically reversible interconversion of the seven-membered ring carbodiimides 35 and 48 and the nitrile ylides 36 and 49 is established. Recyclization of open-chain nitrile ylides is identified as an important mechanism of formation of ring contraction products (N-cyanobenzimidazoles).     

An efficient synthesis of cyclic IDP- and cyclic 8-bromo-IDP-carbocyclic-riboses using a modified Hata condensation method to form an intramolecular pyrophosphate linkage as a key step. An entry to a general method for the chemical synthesis of cyclic ADP-ribose analogues

An efficient synthesis of cyclic IDP-carbocyclic-ribose (3) and its 8-bromo derivative 6, as stable mimics of cyclic ADP-ribose, was achieved, and a condensation reaction with phenylthiophosphate-type substrate 15 or 16 to form an intramolecular pyrophosphate linkage was a key step. N-1-Carbocyclic-ribosylinosine derivative 28 and the corresponding 8-bromo congener 24 were prepared via condensation between N-1-(2,4-dinitrophenyl)inosine derivative 17 and a known optically active carbocyclic amine 18. Compounds 24 and 28 were then converted to the corresponding 5"-phosphoryl-5'-phenylthiophosphate derivatives 15 and 16, respectively, which were substrates for the condensation reaction to form an intramolecular pyrophosphate linkage. Treatment of 8-bromo substrate 15 with I2 or AgNO3 in the presence of molecular sieves 3A (MS 3A) in pyridine at room temperature gave the desired cyclic product 12 quantitatively, while the yield was quite low without MS. The similar reaction of 8-unsubstituted substrate 16 gave the corresponding cyclized product 32 in 81% yield. Acidic treatment of these cyclic pyrophosphates 12 and 32 readily gave the targets 6 and 3, respectively. This result suggests that the construction of N-1-substituted hypoxanthine nucleoside structures from N-1-(2,4-dinitrophenyl)inosine derivatives and the intramolecular condensation by activation of the phenylthiophosphate group with I2 or AgNO3/MS 3A combine to provide a very efficient route for the synthesis of analogues of cyclic ADP-ribose such as 3 and 6. Thus, this may be an entry to a general method for synthesizing biologically important cyclic nucleotides of this type.     

A new highly efficient three-component domino Heck-Diels-Alder reaction with bicyclopropylidene: rapid access to spiro[2.5]oct-4-ene derivatives

Bicyclopropylidene (1) was found to surpass even methyl acrylate (17 a) in its rate of undergoing carbopalladation with aryl- or alkenylpalladium species, leading to substituted allylidenecyclopropanes 5, 7 and 10, mostly in high yields (37-78 %). These dienes and cross-conjugated trienes react in a Diels-Alder mode with dienophiles to give spiro[2.5]octenes 18 a-Ph, 18 b-Ph and 18 a-Vin, respectively, in good yields (89, 69 and 65 %). The overall transformation can be achieved as a one-pot three-component reaction with a variety of dienophiles to furnish the domino Heck-Diels-Alder products 18 regioselectively in most cases in good to very high yields (49-100 %). The reaction of 1 with iodobenzene (2-Ph) and 17 a gave 18 a-Ph in virtually quantitative yield-also on a gram scale-using only 1 mol % of catalyst, and even bromobenzene (22) gave 18 a-Ph in 59 % yield. Bicyclopropylidene (1), in the presence of palladium acetate/triphenylphosphane underwent rearrangement to allylidenecyclopropane (5-H), which in turn dimerized (73 %) in the absence of other reaction partners, or could be trapped by diethyl fumarate (17 c) to give the Diels-Alder adduct 18 c-H in 45 % yield. The coupling of oligoiodobenzenes with 1 and subsequent cycloaddition could be extended to a multicomponent reaction. In this way, 1,4-diiodobenzene (37), 1 and an alkyl acrylate gave the products 38 of a twofold Heck-Diels-Alder reaction in up to 87 % yield, 1,3,5-triiodobenzene (39) reacted in up to 72 % yield and ultimately 1,2,4,5-tetraiodobenzene (41) gave the fourfold domino Heck-Diels-Alder product 42 in 47 % isolated yield, in a single operation in which 12 new carbon-carbon bonds were formed.     

反应时间对淖毛湖煤加氢液化中间产物自由基浓度影响研究

以新疆淖毛湖煤(NMH)为原料,在间歇高压反应釜中进行加氢液化实验,通过电子顺磁共振波谱仪(EPR)分析了加氢液化过程中间产物-沥青质(PAA)自由基浓度随停留时间的变化。结果表明,在实验温度下NMH煤加氢液化总转化率先升高后降低,在60 min达到峰值96.87%,油产率为53.01%;淖毛湖原煤自由基浓度为2.6654×10~(18)/g,PAA自由基浓度在1.2519×10~(18)/g-1.9121×10~(18)/g,随着反应停留时间的延长先上升后下降,中间产物PAA自由基浓度数值可以反映液化反应进行的程度,与油产率变化趋势一致;反应中间产物PAA的g值小于原煤g值(2.00434),在2.00301-2.00403,在液化加氢过程中其g值呈先上升后下降的趋势,与PAA中N、S、O等杂原子成分的变化一致,与元素分析结果相吻合。     

Purines. L. Synthesis and antileukemic activity of the antibiotic guanine 7-oxide and its 9-substituted derivatives.

A full account is given of the first chemical synthesis of the antitumor antibiotic guanine 7-oxide (5) and its 9-substituted derivatives (24a--k and 26). Coupling of appropriate primary amines (17a--e, g--k) with phenacyl bromide (16) produced, after treatment with HCl, the corresponding N-substituted phenacylamine hydrochlorides (18a--e, g--k). A similar phenacylation of 4-amino-l-butanol (21) failed to give the desired compound 18f, so that 21 was heated with 2-bromomethyl-2-phenyl-1,3-dioxolane (20) at 150-155 degrees C for 3h to furnish, after treatment with HCl, the amino ketal hydrochloride 22 in 40% yield. Deketalization of 22 with hot 2 N aqueous HCl afforded 18f in 96% yield. Condensations of the free bases, generated in situ from the hydrochlorides 18a--l and 1N aqueous NaOH, with the chloropyrimidinone 6 were effected in aqueous EtOH at the boiling point for 20 min or at 25-30 degrees C for 3-24h, giving the 6-phenacylamino-4-pyrimidinones 19a-l in 54-90% yields. On treatment with 2N aqueous NaOH at room temperature for 10-60 min, the nitropyrimidinones 19a--k cyclized to provide the 9-substituted guanine 7-oxides 24a--k in 61-98% yields. A similar alkali-treatment of 191 failed to yield guanine 7-oxide (5). However, removal of the 9-(arylmethyl) group from 24i--k was effected with conc. H2SO4 at room temperature for 1-3h in the presence of toluene, producing the target N-oxide 5 in 56-89% yields.(ABSTRACT TRUNCATED AT 250 WORDS)