Synthesis of Macrocyclic Lactones via Ring Transformation of 4‐(ω‐Hydroxyalkyl)‐1,3‐oxazol‐5(4H)‐ones

The synthesis of α‐benzamido‐α‐benzyl lactones 23 of various ring size was achieved either via ‘direct amide cyclization’ by treatment of 2‐benzamido‐2‐benzyl‐ω‐hydroxy‐N,N‐dimethylalkanamides 21 in toluene at 90 – 110° with HCl gas or by ‘ring transformation’ of 4‐benzyl‐4‐(ω‐hydroxyalkyl)‐2‐phenyl‐1,3‐oxazol‐5(4H)‐ones under the same conditions. The precursors were obtained by C‐alkylations of 4‐benzyl‐2‐phenyl‐1,3‐oxazol‐5(4H)‐one ( 15 ) with THP‐ or TBDMS‐protected ω‐hydroxyalkyl iodides. Ring opening of the THP‐protected oxazolones by treatment with Me₂NH followed by deprotection of the OH group gave the diamides 21 , whereas deprotection of the TBDMS series of oxazolones 25 with TBAF followed by treatment with HCl gas led to the corresponding lactones 23 in a one‐pot reaction.     

Cyclocopolymerization of allyl‐acrylate quaternary ammonium salts with diallyldimethylammonium chloride

A series of copolymers of N,N‐dialkyl‐N‐2‐(methoxycarbonyl)allyl allyl ammonium chloride, N,N‐dialkyl‐N‐2‐(ethoxycarbonyl)allyl allyl ammonium chloride, and N,N‐dialkyl‐N‐2‐(t‐butoxycarbonyl)allyl allyl ammonium bromide with diallyldimethylammonium chloride (DADMAC) were prepared in water at 60 °C with 2,2′‐azo‐bis(2‐amidinopropane)dihydrochloride. A strong effect of ester substituents on cyclopolymerization was observed. The methyl and ethyl ester monomers showed high cyclization efficiencies during homopolymerizations and copolymerizations. Unexpectedly, the t‐butyl ester derivatives showed high crosslinking tendencies. Water‐soluble copolymers were obtained only with a decrease in the molar fraction of t‐butyl ester monomer below 30%. Relative reactivities of the allyl‐acrylate monomers in photopolymerizations were compared with the relative reactivity of DADMAC. Allyl‐acrylate monomers were much more reactive than DADMAC; the photopolymerization rate decreased in the following order: N,N‐morpholine‐N‐2‐(t‐butoxycarbonyl)allyl allyl ammonium bromide > N,N‐piperidyl‐N‐2‐(t‐butoxycarbonyl)allyl allyl ammonium bromide > N,N‐dibutyl‐N‐2‐(ethoxycarbonyl)allyl allyl ammonium chloride > N,N‐piperidyl‐N‐2‐(ethoxycarbonyl)allyl allyl ammonium chloride ∼ N,N‐morpholine‐N‐2‐(ethoxycarbonyl)allyl allyl ammonium chloride ∼ N,N‐piperidyl‐N‐2‐(methoxycarbonyl)allyl allyl ammonium chloride > N‐methyl‐N‐butyl‐N‐2‐(ethoxycarbonyl)allyl allyl ammonium chloride. Intrinsic viscosities of the polymers measured in 0.09 M NaCl ranged from 1.06 to 3.20 dL/g. The highest viscosities were obtained for copolymers of the t‐butyl ester monomers with piperidine and morpholine substituents. The copolymer of the t‐butyl ester with piperidine substituent and DADMAC was hydrolyzed in acid to give a polymer with zwitterionic character. © 2001 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 640–649, 2001     

Quinolone analogues 6 [1‐5]. Synthesis of 3‐halogeno‐1‐methylpyridazino[3,4‐b]quinoxalin‐4(1H)‐ones

The reaction of the quinoxaline N‐oxides 7a,b with diethyl ethoxymethylenemalonate gave the 1‐methylpyridazino[3,4‐b]quinoxaline‐4,4‐dicarboxylates 8a,b , whose reaction with N‐bromosuccinimide or N‐chlorosuccinimide afforded the 3‐halogeno‐1‐methylpyridazino[3,4‐b]quinoxaline‐4,4‐dicarboxylates 9a‐d. The reaction of compounds 9a‐d with hydrazine hydrate resulted in hydrolysis and decarboxylation to provide the 3‐halogeno‐1‐methylpyridazino[3,4‐b]quinoxaline‐4‐carboxylates 10a‐d , whose reaction with nitrous acid effected oxidation to furnish the 3‐halogeno‐4‐hydroxy‐1‐methylpyridazino[3,4‐b]quinoxaline‐4‐carboxylates 11a‐d , respectively. The reaction of compounds 11a‐d with hydrazine hydrate afforded the 3‐halogeno‐1‐methylpyridazino[3,4‐b]quinoxalin‐4‐ols 12a‐d , whose oxidation provided the 3‐halogeno‐1‐methylpyridazino[3,4‐b]quinoxalin‐4(1H)‐ones 6a‐d , respectively. Compounds 6a‐d had antifungal activities in vitro.     

Synthesis and characterization of novel biodegradable block copolymer poly(ethylene glycol)‐block‐poly(L‐lactide‐co‐2‐methyl‐2‐carboxyl‐propylene carbonate)

An amphiphilic block copolymer, poly(ethylene glycol)‐block‐poly(L ‐lactide‐co‐2‐methyl‐2‐benzoxycarbonyl‐propylene carbonate) [PEG‐b‐P(LA‐co‐MBC)], was synthesized in bulk by the ring‐opening polymerization of L ‐lactide with 2‐methyl‐2‐benzoxycarbonyl‐propylene carbonate (MBC) in the presence of poly(ethylene glycol) as a macroinitiator with diethyl zinc as a catalyst. The subsequent catalytic hydrogenation of PEG‐b‐P(LA‐co‐MBC) with palladium hydroxide on activated charcoal (20%) as a catalyst was carried out to obtain the corresponding linear copolymer poly(ethyleneglycol)‐block‐poly(L ‐lactide‐co‐2‐methyl‐2‐carboxyl‐propylenecarbonate) [PEG‐b‐P(LA‐co‐MCC)] with pendant carboxyl groups. DSC analysis indicated that the glass‐transition temperature (T_g) of PEG‐b‐P(LA‐co‐MBC) decreased with increasing MBC content in the copolymer, and T_g of PEG‐b‐P(LA‐co‐MCC) was higher than that of the corresponding PEG‐b‐P(LA‐co‐MBC). The in vitro degradation rate of PEG‐b‐P(LA‐co‐MCC) in the presence of proteinase K was faster than that of PEG‐b‐P(LA‐co‐MBC), and the cytotoxicity of PEG‐b‐P(LA‐co‐MCC) to chondrocytes from human fetal arthrosis was lower than that of poly(L ‐lactide). © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 4771–4780, 2005     

Synthesis of Pyrano‐ and Pyrido‐Anellated Pyranosides as Precursors for Nucleoside Analogues

The push‐pull activated methyl (3Z)‐4,6‐O‐benzylidene‐3‐[(methylthio)methylene]‐3‐deoxy‐α‐D‐erythro‐hexopyranosid‐2‐ulose (1) reacted with dialkyl malonate in the presence of potassium carbonate to give the alkyl (2R,4aR,6S,10bS)‐4a,6,8,10b‐tetrahydro‐6‐methoxy‐8‐oxo‐2‐phenyl‐4H‐pyrano[3′,2′:4,5]pyrano[3,2‐d][1,3]dioxine‐9‐carboxylates 2 and 3. Treatment of 1 with 3‐oxo‐N‐phenyl‐butyramide, N‐(4‐methoxy‐phenyl)‐3‐oxo‐butyramide, and 3‐oxo‐N‐o‐tolyl‐butyramide, respectively, in the presence of potassium carbonate and 18‐crown‐6 yielded the (2R,4aR,6S,10bS)‐9‐acetyl‐7‐aryl‐4,4a,7,10b‐tetrahydro‐6‐methoxy‐2‐phenyl[1,3]dioxino‐[4′,5′:5,6]pyrano[3,4‐b]pyridin‐8(6H)‐ones 4–6. (2R,4aR,6S,10bS)‐4,4a,8,10b‐Tetrahydro‐6‐methoxy‐8‐oxo‐2‐phenyl‐4H‐pyrano[3′,2′:4,5]pyrano[3,2‐d][1,3]dioxine‐9‐carboxamide (7) was prepared by anellation reactions of 1 either with malononitrile or with cyanoacetamide.     

Thieno[2,3‐d]pyrimidines in the Synthesis of New Fused Heterocyclic Compounds of Prospective Antitumor and Antioxidant Agents (Part II)

Diethyl azodicarboxylate and 3,4,5,6‐tetrachloro‐1,2‐benzoquinone react with cyclopentano‐ and cycloheptano‐fused thienopyrimidines to form the oxidative dimer of the starting material via S—S bond formation. Reaction of two equivalents of 2,2′‐(cyclohexa‐2′,5′‐diene‐1,4‐diylidene)dimalononitrile with thienopyrimidines afforded 3‐(4′,4′‐dicyanomethylene‐cycloalka[a]‐2,5‐dienyl)‐4‐oxo‐6,7,8,9‐tetrahydro‐5H‐cyclo‐hepta[4,5]‐[1,3]thiazolo[3,2‐a]‐thieno[2,3‐d]pyrimidin‐2‐ylidene‐2‐dicarbonitriles. The thioenopyrimidines react with 2‐[1,3‐dioxo‐1H‐inden‐2(3H)‐ylidene]malononitrile to produce 1,3,5′‐trioxo‐1,3,3′,5′‐tetrahydrospiro‐(indene‐2,2′‐thiazolo[2,3‐b]‐cycloalkyl[b]‐thieno[2,3‐d]pyrimidine)‐3′‐carbonitriles. However, the reaction of thienopyrimidines with 2,3‐dicyano‐1,4‐naphthoquinone proceeded to afford the fused cycloalkyl‐thieno form of naphtho[1,3]thiazolo[3,2‐a]thieno[2,3‐d]pyrimidine‐6.7,12‐triones. Reaction of 2‐hydrazino‐5,6,7,8‐tetrahydrobenzo[b]thieno[2,3‐d]pyrimidine‐4(1H)‐one with dimethyl acetylenedicarboxylate and ethyl propiolate, respectively, afforded cyclohexano‐fused (Z)‐dimethyl 2[(E)‐4‐oxo‐3,4‐dihydrothieno[2,3‐d]pyrimidine‐2(1H)‐ylidene)hydrazono]succinate and thieno‐pyrimidinotriazine. Both oxidative dimers of thienopyrimidines showed high inhibition of Hep‐G2 cell growth compared with the growth of untreated control cells. Moreover, the cycloheptano‐fused thiazinothienopyrimidine indicates a promising specific antitumor agent against Hep‐G2 cells because its IC₅₀ is < 20 μM.     

Reactions of Acid Chlorides/Ketenes with 2‐Substituted 4,5‐Dihydro‐4,4‐dimethyl‐1,3‐thiazoles: Formation of Penam Derivatives

Addition reactions of acid chlorides with various 2‐substituted 4,5‐dihydro‐4,4‐dimethyl‐5‐(methylsulfanyl)‐1,3‐thiazoles under basic conditions were studied. Two kinds of products were obtained from these additions, β‐lactams and non‐β‐lactam adducts. When the reaction was carried out with 4,5‐dihydro‐1,3‐thiazoles with a Ph substituent at C(2), the reaction proceeded via formal [2+2] cycloaddition and led to the correspoding β‐lactam. On the other hand, acid chlorides and 4,5‐dihydro‐1,3‐thiazoles bearing an α‐H‐atom at the C(2)‐substituent underwent C(α)‐ and/or N‐addition reactions and furnished non‐β‐lactam adducts, i.e., C(α)‐ and/or N‐acylated 1,3‐thiazolidines. The attempted transformations of sulfonyl esters of exo‐6‐hydroxy penams to endo‐6‐azido penams failed, although they were successful with mono‐β‐lactams under the same conditions.     

Anionic copolymerization of styrenic‐tipped macromonomers: A route to novel triblock–comb copolymers of styrene and isoprene

The following triblock–comb copolymers of isoprene (I) and styrene (S)—PS‐b‐(PI‐g‐PI)‐b‐PS, PS‐b‐[PI‐g‐(PI‐b‐PS)]‐b‐PS, and (PS‐g‐PS)‐b‐(PI‐g‐PI)‐b‐(PS‐g‐PS) (where PS is polystyrene and PI is polyisoprene)—with PS contents of 20–30% were synthesized with high‐vacuum techniques and the anionic copolymerization of styrenic‐tipped macromonomers with I and S. The macromonomers, prepared by the reaction of living PI or PS with 4‐(chlorodimethylsilyl) styrene, were used without isolation. Molecular characterization by size exclusion chromatography, size exclusion chromatography/two‐angle laser light scattering, and NMR spectroscopy indicated that the triblock–comb copolymers had high molecular and compositional homogeneity. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 4030–4039, 2005     

Synthesiss of novel 3‐(2‐thienyl)‐1,2‐diazepino[3,4‐b]quinoxalines with algicidal activity

The reaction of the quinoxaline N‐oxide 1 with thiophene‐2‐carbaldehyde gave 6‐chloro‐2‐[1‐methyl‐2‐(2‐thienylmethylene)hydrazino]quinoxaline 4‐oxide 5 , whose reaction with 2‐chloroacrylonitrile afforded 8‐chloro‐2,3‐dihydro‐4‐hydroxy‐1‐methyl‐3‐(2‐thienyl)‐1H‐1,2‐diazepino[3,4‐b]quinoxaline‐5‐carbonitrile 6 . The reaction of compound 6 with various alcohols in the presence of a base effected alcoholysis to provide the 5‐alkoxy‐8‐chloro‐2,3,4,6‐tetrahydro‐1‐methyl‐4‐oxo‐3‐(2‐thienyl)‐1H‐1,2‐diazepino[3,4‐b]‐quinoxalines 7a‐d . The reaction of compounds 7a and 7b with diethyl azodicarboxylate effected dehydrogenation to give the 5‐alkoxy‐8‐chloro‐4,6‐dihydro‐1‐methyl‐4‐oxo‐3‐(2‐thienyl)‐1H‐1,2‐diazepino[3,4‐b]‐quinoxalines 8a and 8b , respectively. Compounds 8a and 8b were found to show good algicidal activities against Selenastrum capricornutum and Nitzchia closterium.     

3‐O‐Methylquercetin Glucosides from Ophioglossum pedunculosum and Inhibition of Lipopolysaccharide‐Induced Nitric Oxide Production in RAW 264.7 Macrophages

The three new 3‐O‐methylquercetin glucosides 1 – 3 , together with three known congeners and 3‐O‐methylquercetin, were isolated from the fern Ophioglossum pedunculosum (quercetin=2‐(3,4‐dihydroxyphenyl)‐3,5,7‐trihydroxy‐4H‐1‐benzopyran‐4‐one). The new compounds were identified on the basis of spectroscopic analysis as 5′‐isoprenyl‐3‐O‐methylquercetin 4′,7‐di‐β‐D ‐glucopyranoside ( 1 ), 3‐O‐methylquercetin 4′‐β‐D ‐glucopyranoside 7‐[O‐β‐D ‐glucopyranosyl‐(1→2)‐β‐D ‐glucopyranoside] ( 2 ), and 3‐O‐methylquercetin 7‐[O‐β‐D ‐glucopyranosyl‐(1→2)‐β‐D ‐glucopyranoside] ( 3 ). The effect of the isolated compounds on lipopolysaccharide (LPS)‐induced NO production was evaluated. The inhibitory activity of 3‐O‐methylquercetin derivatives decreased markedly with the increasing number of glucosyl groups in the structures.     

Synthesis and Evaluation of Paromomycin Derivatives Modified at C(4′)

The 2‐amino‐2‐deoxy‐α‐D ‐glucopyranosyl moiety (ring I) of paromomycin was replaced by a 2,4‐diamino‐2,4‐dideoxy‐α‐D ‐glucopyranosyl, 2,4‐diamino‐2,4‐dideoxy‐α‐D ‐galactopyranosyl, 2‐amino‐2‐deoxy‐α‐D ‐galactopyranosyl, or 3,4,5‐trideoxy‐4‐aza‐α‐D ‐erythro‐heptoseptanosyl moiety to investigate the effect of the substituent at C(4′) on the interaction with ribosomal RNA. The triflate 6 was prepared from the key intermediate pentaazido 3′,6′‐dibenzyl ether 5 , and the hexosulose 10 was obtained by oxidation of 5 with Dess–Martin's periodinane. Stereoselective reduction of 10 with NaBH₄ gave the alcohol 11 that was transformed into the triflate 12 . The epimeric hexaazides 7 and 13 were obtained by treating the triflates 6 and 12 , respectively, with tetrabutylammonium azide. Periodate cleavage of glycol 2 yielded the dialdehyde 24 that was reductively aminated with aniline and benzylamine to give the 3,4,5‐trideoxy‐4‐aza‐α‐D ‐erythro‐heptoseptanosides 25 and 26 , respectively. Standard azide reduction and debenzylation yielded 9 (2,4‐diamino‐2,4‐dideoxy‐α‐D ‐galactopyranosyl ring I), 13 (2‐amino‐2‐deoxy‐α‐D ‐galactopyranosyl ring I), 17 (2,4‐diamino‐2,4‐dideoxy‐α‐D ‐glucopyranosyl ring I), and 27 and 28 (3,4,5‐trideoxy‐4‐aza‐α‐D ‐erythro‐heptoseptanosyl ring I). The derivatives 9 and 13 possessing a D ‐galacto‐configured ring I were less active than the corresponding D ‐gluco‐analogues 17 and paromomycin ( 1 ), respectively. The C(4′)‐aminodeoxy derivative 17 (D ‐gluco ring I) and the known 4′‐deoxyparomomycin ( 23 ), prepared by a new route, displayed slightly lower antibacterial activities than paromomycin ( 1 ). Cell‐wall permeability is not responsible for the unexpectedly low activity for 17 , as shown by cell‐free translation assays. The results evidence that the orientation of the substituent at C(4′) is more important than its nature for drug binding and activity.     

Synthesis and reactivity of 6‐methyl‐4H‐furo[3,2c]pyran‐3,4‐dione

An efficient synthesis of 3‐bromoacetyl‐4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one by bromination of dehydroacetic acid in glacial acetic acid is described. Novel 4‐hydroxy‐6‐methyl‐3‐(2‐substituted‐thiazol‐4‐yl)‐2H‐pyran‐2‐ones have been prepared from the reaction of 3‐bromoacetyl‐4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one with thioamides, thiourea, and diphenylthiocarbazone. The condensation reaction of 6‐methyl‐4H‐furo[3,2c]pyran‐3,4‐dione, obtained from the reaction of 3‐bromoacetyl‐4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one with aliphatic amines, with benzaldehydes and acetophenones led to novel 2‐arylidene‐6‐methyl‐2H‐furo[3,2‐c]pyran‐3,4‐diones and 6‐(2‐arylprop‐1‐enyl)‐2H‐furo[3,2‐c]pyran‐3,4‐diones. The structure of all compounds was established by elemental analysis, IR, NMR, and mass spectra. J. Heterocyclic Chem., 2011.     

Synthese,Struktur, Elektrochemie und optische Eigenschaften von alkinylfunktionalisierten 1,3,2‐Diazaborolen und 1,3,2‐Diazaborolidinen

Syntheses, Structures, Electrochemistry and Optical Properties of Alkyne‐Functionalized 1,3,2‐Diazaboroles and 1,3,2‐Diazaborolidenes The reaction of 2‐bromo‐1,3‐ditert‐butyl‐2,3‐dihydro‐1H‐1,3,2‐diazaborole ( 3 ) with lithiated tert‐butyl‐acetylene and lithiated phenylacetylene affords the 2‐alkynyl‐functionalized 1,3,2‐diazaboroles 4 and 5 as a thermolabile colorless oil ( 4 ) or a solid ( 5 ). Similarly 2‐bromo‐1,3‐diethyl‐2,3‐dihydro‐1H‐1,3,2‐benzodiazaborole ( 6 ) was converted into the crystalline 2‐alkynyl‐benzo‐1,3,2‐diazaboroles 7 and 8 by treatment with LiC≡C–tBu or LiC≡CPh, respectively. 2‐Ethynyl‐1,3‐ditert‐butyl‐2,3‐dihydro‐1H‐1,3,2‐diazaborole ( 2 ) was metalated with tert‐butyl‐lithium and subsequently coupled with 2‐bromo‐1,3,‐ditert‐butyl‐2,3‐dihydro‐1H‐1,3,2‐diazaborole ( 3 ) to afford bis(1,3‐ditert‐butyl‐2,3‐dihydro‐1H‐1,3,2‐diazaborol‐2‐yl)acetylene ( 9 ) as thermolabile colorless crystals. Analogously coupling of the lithiated species with 6 or with 2‐bromo‐1,3‐ditert‐butyl‐1,3,2‐diazaborolidine ( 11 ) gave the unsymmetrically substituted acetylenes 10 or 12 , respectively, as colorless solids. Compounds 4 , 5 , 7 – 10 and 12 are characterized by elemental analyses and spectroscopy (IR, ¹H‐, ¹¹B{¹H}, ¹³C{¹H}‐NMR, MS). The molecular structures of 5 , 8 and 9 were elucidated by X‐ray diffraction analyses.     

4‐hydroxy‐6‐methyl‐3‐(5‐phenyl‐2E,4E‐pentadien‐1‐oyl)‐2H‐pyran‐2‐one: Synthesis and reactivity with amines

The synthesis and reactivity studies of 4‐hydroxy‐6‐methyl‐3‐(5‐phenyl‐2E,4E‐pentadien‐1‐oyl)‐2H‐pyran‐2‐one 2 with nucleophiles are reported. Reactions of 2 with hydrazine derivatives gave new pyrazole‐type com pounds while the reaction with ortho‐phenylenediamines yielded 1,5‐benzodiazepines. The reaction of 2 with ethylamine implies the 2H‐pyran‐2‐one ring opening and the formation of a strong conjugated compound 3.     

天然产物 6-脱氧-6氨基葡萄糖甘油糖脂的合成

天然氨基甘油糖脂sn-1,2-dipalmitoyl-3-(N-palmitoyl-6-dehydroxy-6-amino-α-glucosyl)glycerol 3 和 sn-1-palmitoyl-2-myristoyl-3-(N-stearoyl-6-dehydroxy-6-amino-α-glucosyl)glycerol 4 通过简便有效的合成策略首次被合成。其关键步骤为：三氯亚胺酯糖基供体 10 与 (S)-isopropyleneglycerol 在乙醚溶液中发生糖苷化反应,立体选择性的生成3-O-(2,3,4-tri-O-benzyl-6-dehydroxy-6-benzyloxycarbonylamino-α-D- glucopyranoyl)-1,2-O-isopropylene-sn- glycerol 7。中间体 7 经过脱除丙酮叉、与不同的脂肪酸缩合、脱除保护基和选择性的在氨基上酰化,最终得到目标化合物 3 和 4。     

Synthesis and Evaluation of Bioactivity of Thiazolo[3,2‐b]‐[1,2,4]‐triazoles and Isomeric Thiazolo[2,3‐c]‐[1,2,4]‐triazoles

Synthesis of 2‐(o‐nitrophenyl)‐6‐arylthiazolo[3,2‐b]‐[1,2,4]‐triazoles 4 and its isomer 3‐(o‐nitrophenyl)‐5‐arylthiazolo[2,3‐c]‐[1,2,4]‐triazoles 6 has been achieved starting from the appropriate 1‐(o‐nitrobenzoyl)‐3‐thiosemicarbazide 1 . Compound 1 on condensation with α‐haloketones gives 2‐(o‐nitrobenzoyl)hydrazino‐4‐arylthiazole hydrobromide 5 , which, on cyclization with POCl₃, affords thiazolo[3,2‐b]‐[1,2,4]‐triazoles 6 and not the isomeric thiazolo[3,2‐b]‐[1,2,4]‐triazoles 4 . This has been established by an unequivocal synthesis of 4 through polyphosphoric acid cyclization of 5‐aroylmethylmercapto‐3‐o‐nitrophenyl‐[1,2,4]‐triazole 3 . Compound 3 was synthesized by condensation of α‐haloketones with 5‐mercapto‐3‐(o‐nitrophenyl)‐[1,2,4]‐triazole 2 , obtained cyclization of 2‐(o‐nitrobenzoyl)hydrazinecarbothioamide 1 with NaOH. The antibacterial and antifungal activities of some of the compounds have also been evaluated.     

S‐endo‐2‐Norbornyl‐N‐n‐butylcarbamate as a Potential Pseudomonas Lipase Inhibitor to Probe the Enantioselectivity of the Enzyme by Kinetic and Molecular Docking Evaluation

Obesity is a complex health issue and it can cause many health and social problems. Previous studies reported that lipase is a main target for obesity treatment. We synthesized R‐exo‐2‐norbornyl‐N‐n‐butylcarbamate and S‐exo‐2‐norbornyl‐N‐n‐butylcarbamate as potential pseudomonas lipase inhibitors to probe the enantioselectivity of the enzyme and demonstrated that R‐exo‐2‐norbornyl‐N‐n‐butylcarbamate had better enzyme enantioselectivity, ki and the docking model with Pseudomonas species lipase in our previous studies. In this article, we reported the property of the Pseudomonas species lipase inhibitors, R‐and S‐endo‐2‐norbornyl‐N‐n‐butylcarbamate and compared the docking models of these two compounds with R‐ and S‐exo‐2‐norbornyl‐N‐n‐butylcarbamates by AutoDock. We found that S‐endo‐2‐norbornyl‐N‐n‐butylcarbamate has the best enantioselectivity, ki and docking model and this study could provide useful information about enzyme enantioselectivity for the development of Pseudomonas species lipase inhibitors for obesity treatment.     

Synthesis of New Conjugates of Modified Podophyllotoxin and Stavudine

To find podophyllotoxin compounds with superior bioactivitiy and less toxicity, a series of novel conjugates of ring‐A‐modified 4‐epipodophyllotoxin and stavudine with amino acids as spacers were synthesized, i.e., the N‐[(2′,3′‐didehydro‐3′‐deoxythymidin‐5′‐O‐yl)carbonyl]‐substituted L ‐amino acid rel‐(3aR,4S,9R,9aR)‐1,3,3a,4,9,9a‐hexahydro‐6,7‐dimethoxy‐1‐oxo‐9‐(3,4,5‐trimethoxyphenyl)naphtho[2,3‐c]furan‐4‐yl esters 8a – 8f .     

Synthesis of New Chromeno[4,3‐b]pyrazolo[4,3‐e]pyridines Derivatives with Antimicrobial Evaluation

A series of 2‐oxo‐2,5‐dihydro‐1H‐chromeno[4,3‐b]pyridine derivatives were obtained by using a one‐pot three component reaction of 2,2‐disubstituted chroman‐4‐one with aromatic aldehydes and 2‐cyanoacetamide in the presence of sodium hydroxide under solvent‐free conditions. Heating chromenopyridine derivatives with phosphoryl chloride gave the corresponding chloro derivatives. The reaction of the chloro derivatives with hydrazine hydrate afforded dihydrochromeno[4,3‐b]pyrazolo[4,3‐e]pyridines derivatives. Condensation of the dimethyl derivative compound with the aromatic aldehydes gave 8‐Arylideneamino‐6,6‐dimethyl‐10H‐chromeno[4,3‐b]pyrazolo[4,3‐e]pyridine.     

Three New ent‐Kaurane Diterpenoids from Siegesbeckia pubescens

Three new ent‐kaurane glucopyranosides, 2‐O‐[β‐D ‐apiofuranosyl‐(1→3)‐2‐O‐isovaleryl‐β‐D ‐glucopyranosyl]‐4‐epi‐atractyligenin ( 1 ), 2‐O‐[β‐D ‐apiofuranosyl‐(1→3)‐2‐O‐isovaleryl‐β‐D ‐glucopyranosyl]atractyligenin ( 2 ), and 2‐O‐[β‐D ‐apiofuranosyl‐(1→3)‐2‐O‐(3‐methylpentanoyl)‐β‐D ‐glucopyranosyl]‐4‐epi‐atractyligenin ( 3 ), along with 2‐O‐(2‐O‐isovaleryl‐β‐D ‐glucopyranosyl)‐4‐epi‐atractyligenin ( 4 ), were isolated for the first time from the aerial parts of Siegesbeckia pubescens. The structures were established by extensive spectroscopic analyses including 1D ‐ and 2D ‐NMR (HSQC, HMBC, and ROESY), and HR‐ESI‐MS, and by comparison with published data.