As a versatile type of enzyme,carboxylic acid reductases(CAR)can not only reduce various carboxylic acids to aldehydes in cooperation with cofactors ATP and NADPH but also catalyze the synthesis of amides and esters i...As a versatile type of enzyme,carboxylic acid reductases(CAR)can not only reduce various carboxylic acids to aldehydes in cooperation with cofactors ATP and NADPH but also catalyze the synthesis of amides and esters in the absence of NADPH.Here,we report an intramolecular cyclization catalyzed by CAR only with the use of ATP to transform amino acids into diverse lactams,includingγ-/δ-/ε-lactams and chiral derivatives thereof.The observed wide substrate scope and selectivity enable potential applications to be implemented.Our results demonstrate that CAR-catalyzed lactamization is a promising approach for the synthesis of chiral lactam com-pounds under mild conditions,thereby enriching the toolbox for the biosynthesis of lactams as a viable alternative to purely chemical procedures.展开更多
Using 2-bromo-1-methylpyridimium iodide as carboxyl activating agent, 10 ansa-macrolactams were prepared conveniently from the corresponding seco-precursor w-aminoacids in the yields of 78-2%.
A new oxidative N-heterocyclic carbene(NHC)-catalyzed high-order[7+3]annulation reaction ofγ-indolyl phenols as 1,7-dinucleophiles andα,β-alkynals with the aid of Sc(OTf)_(3)is reported,enabling the highly regiosel...A new oxidative N-heterocyclic carbene(NHC)-catalyzed high-order[7+3]annulation reaction ofγ-indolyl phenols as 1,7-dinucleophiles andα,β-alkynals with the aid of Sc(OTf)_(3)is reported,enabling the highly regioselective access to unprecedented polyarene-fused ten-membered lactams bearing a bridged aryl-aryl-indole scaffold in moderate to good yields.This protocol demonstrates a broad substrate scope,good compatibility with substituents and complete regioselectivity,providing an organocatalytic modular synthetic strategy for creating medium-sized lactams.展开更多
Bridged polycyclic lactams are important structural units in organic functional materials,natural products,and pharmaceuticals.A flexible and efficient anion cascade reaction was developed for the preparation of bridg...Bridged polycyclic lactams are important structural units in organic functional materials,natural products,and pharmaceuticals.A flexible and efficient anion cascade reaction was developed for the preparation of bridged polycyclic lactams from readily available malonamides and 1,4‑dien-3-ones.Various highly substituted bridged polycyclic lactams were synthesized in good to excellent yields by tandem nucleophilic sequences in the presence of t BuOK in commercially available EtOH solvent at 60℃.Notably,the simple reactions can be run on a gram scale.Mechanistically,bis-Michael addition reaction and hemiaminalization reactions are involved in the tandem transformation.展开更多
A new aristololactam, aristololactam Ⅶ （1）, was isolated from the root and rhizome of Asarum maximum Hemsl. On the basis of spectroscopic analysis, its structure was identified as 10-amino-7,8-dimethoxy-3,4-methyle...A new aristololactam, aristololactam Ⅶ （1）, was isolated from the root and rhizome of Asarum maximum Hemsl. On the basis of spectroscopic analysis, its structure was identified as 10-amino-7,8-dimethoxy-3,4-methylenedioxy-phenanthrene-1- earboxylie acid laetam.展开更多
Ru(bpy)3]2+-cored supramolecular organic framework SMOF-1, assembled from a [Ru(bpy)3]2+-derived hexaarmed molecule and cucurbit[8]uril, has been demonstrated to heterogeneously catalyze visible light-induced reductio...Ru(bpy)3]2+-cored supramolecular organic framework SMOF-1, assembled from a [Ru(bpy)3]2+-derived hexaarmed molecule and cucurbit[8]uril, has been demonstrated to heterogeneously catalyze visible light-induced reduction of phenyl, benzyl, 2-phenylethyl and 3-phenylpropyl azides in acetonitrile to produce the corresponding amines in good to high yields. For the last two kinds of azides that bear a CO2Me group at the para-position of the benzene ring, cascade reactions take place to generate the corresponding lactams in high yields. Compared with homogeneous control [Ru(bpy)3]Cl2, SMOF-1 exhibits remarkably increased photocatalysis activity as a result of synergistic effect of the [Ru(bpy)3]2+ units that form cubic cages to host the azide molecules and related intermediates. Moreover, SMOF-1 displays high recyclability and considerable photocatalysis activity after 3 to 12 runs.展开更多
Penicillin-binding proteins（PBPs） are the target of β-lactam antibiotics（the major treatment for Streptococcus pneumoniae infections）,and mutations in PBPs are considered as a primary mechanism for the developmen...Penicillin-binding proteins（PBPs） are the target of β-lactam antibiotics（the major treatment for Streptococcus pneumoniae infections）,and mutations in PBPs are considered as a primary mechanism for the development of β-lactam resistance in S.pneumoniae.This study was conducted to investigate the mutations in the PBPs of clinical S.pneumoniae isolates in Hangzhou,China,in correlation with β-lactam resistance.Results showed that 19 F was the predominant serotype（7/27） and 14 of the S.pneumoniae isolates were resistant to both penicillin G and cephalosporin.Genotyping results suggested that β-lactam-resistant isolates primarily exhibited single-site mutations in both the STMK and SRNVP motifs of pbp1 a in combination with double-site mutations in the STMK motif of pbp2 x,which might be the primary mechanisms underlying the β-lactam resistance of the isolates in this study.展开更多
Three new limonoid-type triterpenoids,namely toonasins A–C(1–3)with a rare lactam E ring,along with six known compounds(4–9)were isolated from the barks of Toona sinensis.The structures of new compounds were elucid...Three new limonoid-type triterpenoids,namely toonasins A–C(1–3)with a rare lactam E ring,along with six known compounds(4–9)were isolated from the barks of Toona sinensis.The structures of new compounds were elucidated by interpretation of spectroscopic data,and the relative configuration of compound 1 was further characterized by X-ray crystallographic analyses.The isolated compounds were evaluated for their cytotoxic activities against five human tumor cell lines(HL-60,SMMC-7721,A-549,MCF-7 and SW480),and compounds 3 and 5 showed weak cytotoxicities.展开更多
The mechanism of the formation of a key tricyclic lactam intermediate 3 was studied. It was found that the E-form compound 3 was transformed from the Z-form compound 4. The formation of 4 was a kinetically controlle...The mechanism of the formation of a key tricyclic lactam intermediate 3 was studied. It was found that the E-form compound 3 was transformed from the Z-form compound 4. The formation of 4 was a kinetically controlled process while the formation of 3 was a thermodynamically favorable one. A possible mechanism was given in this paper.展开更多
Mass spectrometric behaviour of 2,2a,3,4-tetrahydro-4-methyl-2a-phenyl-2-(thiophen-2-yl)-1H-azeto[2,1-d][1,5]benzothiazepin-1-one-5-oxide and 2,3-dihydro-2,4-diphenyl-1,5-benzothiazepine-1-oxide/-1,1-dioxide have been...Mass spectrometric behaviour of 2,2a,3,4-tetrahydro-4-methyl-2a-phenyl-2-(thiophen-2-yl)-1H-azeto[2,1-d][1,5]benzothiazepin-1-one-5-oxide and 2,3-dihydro-2,4-diphenyl-1,5-benzothiazepine-1-oxide/-1,1-dioxide have been studied with the aid of mass-analyzed ion kinetic energy spectrometry and accurate mass measurements under electron impact ionization. The monooxide derivatives showed a tendency to eliminate an alkene or an oxygen atom. 1H-Azeto[2,1-d][1,5]benzothiazepin-1-one-5-oxide could also eliminate the thiophen-2-ylketene molecule via a reverse [2+2] cycloaddition. 2,3-Dihydro-2,4-diphenyl-1,5-benzothiazepine-1-oxide/-1,1-dioxide could eliminate SO_2 or SO, respectively. The structure of 2,2a,3,4-tetrahydro-4-methyl-2a-phenyl-2-(thiophen-2-yl)-1H-azeto[2,1-d][1,5]benzothiazepin-1-one-5-oxide was identified on the basis of its fragmentation. The identification was supported by the fragmentations of model compound, 2,3-dihydro-2,4-diphenyl-1,5-benzothiazepine-1-oxide/-1,1-dioxide.展开更多
The crystal of the title compound C, C 30 H 30 N 2O 3S has been prepared by reaction of 1,5 benzothiazepine with N protected glycine and determined by X ray single crystal diffraction. Crystal data:...The crystal of the title compound C, C 30 H 30 N 2O 3S has been prepared by reaction of 1,5 benzothiazepine with N protected glycine and determined by X ray single crystal diffraction. Crystal data: M r =498.62, triclinic with P 1 space group, a=10.880(2), b=13.955(3), c=9.537(2), α=99.34(3)°, β=110.43(3)°, γ=88 56(3)°, V=1338.2(5) 3, F(000)=528, λ (Mo Kα)=0.71073, Z=2, D c =1 237g/cm 3, μ =0.154mm -1 . Final R=0.0453, wR =0.1256 for 3491 observed reflections 〔 I>2σ(I) 〕. Structure analysis reveals that the substituents at C(23) and C(7) in four membered ring are located on the same side. The conformation of seven membered ring is chair like.展开更多
The Beckmann rearrangement of cyclohexanone oxime was achieved by the combined use of cobalt salt and Lewis acids co-catalysts (each 10 mol%). Various combinations of cobalt salts and Lewis acids gave lactams in a sat...The Beckmann rearrangement of cyclohexanone oxime was achieved by the combined use of cobalt salt and Lewis acids co-catalysts (each 10 mol%). Various combinations of cobalt salts and Lewis acids gave lactams in a satisfactory yield under mild conditions. This method makes it possible to reduce undesirable byproducts.展开更多
A mild two-step method was used to cleave the lactam ring of the tricyclic intermediate 1. A key racemic amino alcohol precursor 5 for the construction of Et-743 skeleton was synthesized from 1 through four steps in ...A mild two-step method was used to cleave the lactam ring of the tricyclic intermediate 1. A key racemic amino alcohol precursor 5 for the construction of Et-743 skeleton was synthesized from 1 through four steps in total yield of 47%.展开更多
Anticancer antibiotics have made a successful impact in the field of chemotherapeutics. For most of them, DNA is the molecular target. Some act as DNA intercalators or some prevent DNA repair among other mechanisms of...Anticancer antibiotics have made a successful impact in the field of chemotherapeutics. For most of them, DNA is the molecular target. Some act as DNA intercalators or some prevent DNA repair among other mechanisms of actions, they are seen to have. The major disadvantages of these drugs though are the constant side effects and toxicities. With more focus on discovery of new drugs with newer scaffolds, the urge to discover and modify anticancer antibiotics is being lost. Modifications or even the wider research can yield newer better drugs for clinical use. The review here discusses the current antibiotic therapeutics, newer discoveries in the field as well ideas for future research.展开更多
A limited number of researches have been reported to apply the Arrhenius equation to study the relationship between drugs and its degradation products so far.In the present work,the thermal degradation kinetics of lys...A limited number of researches have been reported to apply the Arrhenius equation to study the relationship between drugs and its degradation products so far.In the present work,the thermal degradation kinetics of lysine hydrochloride solutions for injection,the special solvent for ademetionine 1,4-butanedisulfonate(SAM)for injection,was investigated at selected temperatures and pH values.The main degradation product of lysine was separated,purified,and confirmed as lysine lactam.A reversed-phase high performance liquid chromatographic(RP-HPLC)method without derivation was developed for the simultaneous determination of lysine and lysine lactam.The results confirmed that both the lysine degradation and lysine lactam generation followed zero-order reaction kinetics.The degradation and generation rate constants increased with increasing temperatures and decreasing pH values.The temperature-dependent degradation and generation reaction could be sufficiently modeled on the Arrhenius equation with the activation energy of 80.14 and 83.22 kJ/mol,respectively.Meanwhile,a linear relationship existed between the amount of lysine degradation and lysine lactam generation since the approximate activation energy.Considering there could be other side effects,we established an upper limit of lysine lactam(500 mg/ml),as the acceptable criteria for stability to estimate the shelf life together with lysine,which made the prediction more accurate and credible.Extrapolation data demonstrated that the lysine hydrochloride solutions for injection could be stable for two years stored at room temperature.展开更多
We describe the design and execution of a novel synthetic route to the tricyclic core of haliclonin A,a tetracyclic marine natural product.The approach features Bachi＇s thiol-medicated free radical cyclization of alk...We describe the design and execution of a novel synthetic route to the tricyclic core of haliclonin A,a tetracyclic marine natural product.The approach features Bachi＇s thiol-medicated free radical cyclization of alkenyl isocyanide to build the bridged ring system,and ring-closing metathesis（RCM） reaction to form the macrocycle.Execution of the synthetic plan ultimately resulted in a diazatricyclic compound.By means of 2D NMR techniques,the structure of this compound was revealed to an unexpected product 8.Analysis of the synthetic pathways allowed concluding that the unexpected product is a result of an ＂unexpected＂ migration of olefinic bond during dioxolanation of the 2-cyclohexenone derivative 7.This investigation also resulted in a concise construction of the functionalized hexahydro-1H-isoindole-1,5（4H）-dione 12 and the macrocyclic tricyclic ring system 8.展开更多
The emerging trend of multidrug resistance is becoming a major threat to community acquired and nosocomial infections,worldwide[1].The carbapenems are used as last-source drugs because of increasing resistance against...The emerging trend of multidrug resistance is becoming a major threat to community acquired and nosocomial infections,worldwide[1].The carbapenems are used as last-source drugs because of increasing resistance against beta-lactam groups of antibiotics due to its excessive use to treat wide range of infections[2].The展开更多
基金supported by the National Key Research and Development Program of China(No.2019YFA0905100)the National Natural Science Foundation of China(No.31900909)+1 种基金the Natural Science Foundation Applying a system of Tianjin(No.21JCJQJC00110)and Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project(No.TSBICIP-CXRC-009)Mr Qu also thanks financial support from Youth Innovation Promotion Association,CAS(No.2021175).
文摘As a versatile type of enzyme,carboxylic acid reductases(CAR)can not only reduce various carboxylic acids to aldehydes in cooperation with cofactors ATP and NADPH but also catalyze the synthesis of amides and esters in the absence of NADPH.Here,we report an intramolecular cyclization catalyzed by CAR only with the use of ATP to transform amino acids into diverse lactams,includingγ-/δ-/ε-lactams and chiral derivatives thereof.The observed wide substrate scope and selectivity enable potential applications to be implemented.Our results demonstrate that CAR-catalyzed lactamization is a promising approach for the synthesis of chiral lactam com-pounds under mild conditions,thereby enriching the toolbox for the biosynthesis of lactams as a viable alternative to purely chemical procedures.
基金Project supported by the National Natural Science Foundation of China.
文摘Using 2-bromo-1-methylpyridimium iodide as carboxyl activating agent, 10 ansa-macrolactams were prepared conveniently from the corresponding seco-precursor w-aminoacids in the yields of 78-2%.
基金National Natural Science Foundation of China(Nos.21971090 and 22271123)the NSF of Jiangsu Province(No.BK20230201)+1 种基金the Natural Science Foundation of Jiangsu Education Committee(No.22KJB150024)the Natural Science Foundation of Jiangsu Normal University(No.21XSRX010)。
文摘A new oxidative N-heterocyclic carbene(NHC)-catalyzed high-order[7+3]annulation reaction ofγ-indolyl phenols as 1,7-dinucleophiles andα,β-alkynals with the aid of Sc(OTf)_(3)is reported,enabling the highly regioselective access to unprecedented polyarene-fused ten-membered lactams bearing a bridged aryl-aryl-indole scaffold in moderate to good yields.This protocol demonstrates a broad substrate scope,good compatibility with substituents and complete regioselectivity,providing an organocatalytic modular synthetic strategy for creating medium-sized lactams.
基金National Natural Science Foundation of China(NSFC,Nos.21772032,21877206,and 22101074)the 111 Project(No.D17007)+3 种基金Excellent Youth Foundation of Henan Scientific Committee(No.222300420012)China Postdoctoral Science Foundation(No.2019M660173)the Natural Science Foundation of Henan Province(No.202300410233)Henan Key Laboratory of Organic Functional Molecules and Drug Innovation for financial support。
文摘Bridged polycyclic lactams are important structural units in organic functional materials,natural products,and pharmaceuticals.A flexible and efficient anion cascade reaction was developed for the preparation of bridged polycyclic lactams from readily available malonamides and 1,4‑dien-3-ones.Various highly substituted bridged polycyclic lactams were synthesized in good to excellent yields by tandem nucleophilic sequences in the presence of t BuOK in commercially available EtOH solvent at 60℃.Notably,the simple reactions can be run on a gram scale.Mechanistically,bis-Michael addition reaction and hemiaminalization reactions are involved in the tandem transformation.
基金National Natural Science Foundation of China (Grant No. 30371748)the 985 Project of Peking University and the National Eleventh Five-year Key Technologies R&D Program of China (Grant No. 2006BAI14B01)
文摘A new aristololactam, aristololactam Ⅶ （1）, was isolated from the root and rhizome of Asarum maximum Hemsl. On the basis of spectroscopic analysis, its structure was identified as 10-amino-7,8-dimethoxy-3,4-methylenedioxy-phenanthrene-1- earboxylie acid laetam.
基金supported by the National Natural Science Foundation of China (Nos. 21432004 and 21890732)
文摘Ru(bpy)3]2+-cored supramolecular organic framework SMOF-1, assembled from a [Ru(bpy)3]2+-derived hexaarmed molecule and cucurbit[8]uril, has been demonstrated to heterogeneously catalyze visible light-induced reduction of phenyl, benzyl, 2-phenylethyl and 3-phenylpropyl azides in acetonitrile to produce the corresponding amines in good to high yields. For the last two kinds of azides that bear a CO2Me group at the para-position of the benzene ring, cascade reactions take place to generate the corresponding lactams in high yields. Compared with homogeneous control [Ru(bpy)3]Cl2, SMOF-1 exhibits remarkably increased photocatalysis activity as a result of synergistic effect of the [Ru(bpy)3]2+ units that form cubic cages to host the azide molecules and related intermediates. Moreover, SMOF-1 displays high recyclability and considerable photocatalysis activity after 3 to 12 runs.
基金supported by Grants from the National Natural Sciences Foundation of China[81772232]Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents
文摘Penicillin-binding proteins（PBPs） are the target of β-lactam antibiotics（the major treatment for Streptococcus pneumoniae infections）,and mutations in PBPs are considered as a primary mechanism for the development of β-lactam resistance in S.pneumoniae.This study was conducted to investigate the mutations in the PBPs of clinical S.pneumoniae isolates in Hangzhou,China,in correlation with β-lactam resistance.Results showed that 19 F was the predominant serotype（7/27） and 14 of the S.pneumoniae isolates were resistant to both penicillin G and cephalosporin.Genotyping results suggested that β-lactam-resistant isolates primarily exhibited single-site mutations in both the STMK and SRNVP motifs of pbp1 a in combination with double-site mutations in the STMK motif of pbp2 x,which might be the primary mechanisms underlying the β-lactam resistance of the isolates in this study.
基金the National Knowledge Innovation of CAS(No.KSCX2-YW-G-038)the Foundation of State Key Laboratory of Phytochemistry and Plant Resources in West China(P2015-ZZ09)。
文摘Three new limonoid-type triterpenoids,namely toonasins A–C(1–3)with a rare lactam E ring,along with six known compounds(4–9)were isolated from the barks of Toona sinensis.The structures of new compounds were elucidated by interpretation of spectroscopic data,and the relative configuration of compound 1 was further characterized by X-ray crystallographic analyses.The isolated compounds were evaluated for their cytotoxic activities against five human tumor cell lines(HL-60,SMMC-7721,A-549,MCF-7 and SW480),and compounds 3 and 5 showed weak cytotoxicities.
文摘The mechanism of the formation of a key tricyclic lactam intermediate 3 was studied. It was found that the E-form compound 3 was transformed from the Z-form compound 4. The formation of 4 was a kinetically controlled process while the formation of 3 was a thermodynamically favorable one. A possible mechanism was given in this paper.
文摘Mass spectrometric behaviour of 2,2a,3,4-tetrahydro-4-methyl-2a-phenyl-2-(thiophen-2-yl)-1H-azeto[2,1-d][1,5]benzothiazepin-1-one-5-oxide and 2,3-dihydro-2,4-diphenyl-1,5-benzothiazepine-1-oxide/-1,1-dioxide have been studied with the aid of mass-analyzed ion kinetic energy spectrometry and accurate mass measurements under electron impact ionization. The monooxide derivatives showed a tendency to eliminate an alkene or an oxygen atom. 1H-Azeto[2,1-d][1,5]benzothiazepin-1-one-5-oxide could also eliminate the thiophen-2-ylketene molecule via a reverse [2+2] cycloaddition. 2,3-Dihydro-2,4-diphenyl-1,5-benzothiazepine-1-oxide/-1,1-dioxide could eliminate SO_2 or SO, respectively. The structure of 2,2a,3,4-tetrahydro-4-methyl-2a-phenyl-2-(thiophen-2-yl)-1H-azeto[2,1-d][1,5]benzothiazepin-1-one-5-oxide was identified on the basis of its fragmentation. The identification was supported by the fragmentations of model compound, 2,3-dihydro-2,4-diphenyl-1,5-benzothiazepine-1-oxide/-1,1-dioxide.
文摘The crystal of the title compound C, C 30 H 30 N 2O 3S has been prepared by reaction of 1,5 benzothiazepine with N protected glycine and determined by X ray single crystal diffraction. Crystal data: M r =498.62, triclinic with P 1 space group, a=10.880(2), b=13.955(3), c=9.537(2), α=99.34(3)°, β=110.43(3)°, γ=88 56(3)°, V=1338.2(5) 3, F(000)=528, λ (Mo Kα)=0.71073, Z=2, D c =1 237g/cm 3, μ =0.154mm -1 . Final R=0.0453, wR =0.1256 for 3491 observed reflections 〔 I>2σ(I) 〕. Structure analysis reveals that the substituents at C(23) and C(7) in four membered ring are located on the same side. The conformation of seven membered ring is chair like.
文摘The Beckmann rearrangement of cyclohexanone oxime was achieved by the combined use of cobalt salt and Lewis acids co-catalysts (each 10 mol%). Various combinations of cobalt salts and Lewis acids gave lactams in a satisfactory yield under mild conditions. This method makes it possible to reduce undesirable byproducts.
文摘A mild two-step method was used to cleave the lactam ring of the tricyclic intermediate 1. A key racemic amino alcohol precursor 5 for the construction of Et-743 skeleton was synthesized from 1 through four steps in total yield of 47%.
文摘Anticancer antibiotics have made a successful impact in the field of chemotherapeutics. For most of them, DNA is the molecular target. Some act as DNA intercalators or some prevent DNA repair among other mechanisms of actions, they are seen to have. The major disadvantages of these drugs though are the constant side effects and toxicities. With more focus on discovery of new drugs with newer scaffolds, the urge to discover and modify anticancer antibiotics is being lost. Modifications or even the wider research can yield newer better drugs for clinical use. The review here discusses the current antibiotic therapeutics, newer discoveries in the field as well ideas for future research.
文摘A limited number of researches have been reported to apply the Arrhenius equation to study the relationship between drugs and its degradation products so far.In the present work,the thermal degradation kinetics of lysine hydrochloride solutions for injection,the special solvent for ademetionine 1,4-butanedisulfonate(SAM)for injection,was investigated at selected temperatures and pH values.The main degradation product of lysine was separated,purified,and confirmed as lysine lactam.A reversed-phase high performance liquid chromatographic(RP-HPLC)method without derivation was developed for the simultaneous determination of lysine and lysine lactam.The results confirmed that both the lysine degradation and lysine lactam generation followed zero-order reaction kinetics.The degradation and generation rate constants increased with increasing temperatures and decreasing pH values.The temperature-dependent degradation and generation reaction could be sufficiently modeled on the Arrhenius equation with the activation energy of 80.14 and 83.22 kJ/mol,respectively.Meanwhile,a linear relationship existed between the amount of lysine degradation and lysine lactam generation since the approximate activation energy.Considering there could be other side effects,we established an upper limit of lysine lactam(500 mg/ml),as the acceptable criteria for stability to estimate the shelf life together with lysine,which made the prediction more accurate and credible.Extrapolation data demonstrated that the lysine hydrochloride solutions for injection could be stable for two years stored at room temperature.
基金the National Natural Science Foundation of China(No.21472153)the National Basic Research Program(973 Program)of China(No.2010CB833200)+1 种基金the SKL of Xiamen University(No.201509)the Program for Changjiang Scholars and Innovative Research Team in University of Ministry of Education,China,for financial support
文摘We describe the design and execution of a novel synthetic route to the tricyclic core of haliclonin A,a tetracyclic marine natural product.The approach features Bachi＇s thiol-medicated free radical cyclization of alkenyl isocyanide to build the bridged ring system,and ring-closing metathesis（RCM） reaction to form the macrocycle.Execution of the synthetic plan ultimately resulted in a diazatricyclic compound.By means of 2D NMR techniques,the structure of this compound was revealed to an unexpected product 8.Analysis of the synthetic pathways allowed concluding that the unexpected product is a result of an ＂unexpected＂ migration of olefinic bond during dioxolanation of the 2-cyclohexenone derivative 7.This investigation also resulted in a concise construction of the functionalized hexahydro-1H-isoindole-1,5（4H）-dione 12 and the macrocyclic tricyclic ring system 8.
基金supported by internal funds of Bioteclmology and DBT grant.BT/PR11453/BID/07/296/2009 to AUK
文摘The emerging trend of multidrug resistance is becoming a major threat to community acquired and nosocomial infections,worldwide[1].The carbapenems are used as last-source drugs because of increasing resistance against beta-lactam groups of antibiotics due to its excessive use to treat wide range of infections[2].The
