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1.
Ke‐Na Feng Yan‐Long Yang Yu‐Xing Xu Yue Zhang Tao Feng Sheng‐Xiong Huang Ji‐Kai Liu Ying Zeng 《Angewandte Chemie (International ed. in English)》2020,59(18):7209-7213
Vibralactone is isolated from the basidiomycete fungus Boreostereum vibrans as one of the strongest lipase inhibitors. Its unusual β‐lactone‐fused bicycle is derived from an aryl ring moiety by an oxidative ring‐expansion prior to an intramolecular cyclization. Herein, we report the discovery of the cyclase VibC which belongs to the α/β‐hydrolase superfamily and is involved in the vibralactone biosynthesis. Biochemical and crystal studies suggest that VibC may catalyze an aldol or an electrocyclic reaction initiated by the Ser‐His‐Asp catalytic triad. For the aldol and pericyclic chemistry in living cells, VibC is a unique hydrolase performing the carbocycle formation of an oxepinone to a fused bicyclic β‐lactone. This presents a naturally occurring, new enzymatic reaction in both aldol and hydrolase (bio)chemistry that will guide future exploitation of these enzymes in synthetic biology for chemical‐diversity expansion of natural products. 相似文献
2.
Natalie L. Harvey Dr. Joanna Krysiak Dr. Supakarn Chamni Dr. Sung Wook Cho Prof. Dr. Stephan A. Sieber Prof. Dr. Daniel Romo 《Chemistry (Weinheim an der Bergstrasse, Germany)》2015,21(4):1425-1428
An eleven‐step synthesis of (±)‐spongiolactone from 1,3‐cyclohexanedione is reported that relies on a diastereoselective, nucleophile‐catalyzed aldol lactonization (NCAL) process with an advanced ketoacid intermediate that installed the anticipated β‐lactone pharmacophore of the natural product. In addition, a stereoselective cyclohexenyl zinc addition to a substituted cyclohexanone simultaneously installed two fully substituted vicinal stereocenters. The reported synthesis enabled preliminary structure–activity studies that revealed a regio‐ and stereoisomeric derivative of spongiolactone with greater antiproliferative activity towards a leukemia (K562) cell line. Furthermore, unusual antiproliferative selectivity of these spongiolactone derivatives toward the K562 cell line was observed with no inhibition of the breast, liver, and lung cancer cell lines tested. 相似文献
3.
Recent Developments in Total Syntheses of Cephalosporolides,Penisporolides, and Ascospiroketals 下载免费PDF全文
Dr. Hongliang Yao Jian Wang Prof. Dr. Rongbiao Tong 《Chemical record (New York, N.Y.)》2017,17(11):1109-1123
The possible biogenetic connection of the 10‐membered lactone (decanolide) and the tricyclic [5,5]‐spiroacetal‐cis‐fused‐γ‐lactone (SAFL) natural products was proposed by Hanson in 1985. Mimicking such biosynthetic hypothesis led us to develop a general synthetic strategy for the total syntheses of both decanolide‐type cephalosporolides and SAFL‐type natural products. This biomimetic strategy features two key transformations: i) oxidative ring expansion of bicyclic β‐hydroxy tetrahydropyrans to the decanolides and ii) ring contraction rearrangement of the decanolides to the tricyclic SAFLs. In particular, the phenol derivatives are exploited as the starting materials for the decanolides and then the SAFLs. The successful biomimetic total synthesis allows us to revise the structures and biosynthetic hypothesis of several natural products, along with development of an NMR analysis method for determination of the relative stereochemistry of SAFL‐type compounds. In addition, this account will summarize recent synthetic work by other research groups. 相似文献
4.
Ruben Bartholomäus Fabian Dommershausen Dr. Markus Thiele Narayan S. Karanjule Dr. Klaus Harms Prof. Dr. Ulrich Koert 《Chemistry (Weinheim an der Bergstrasse, Germany)》2013,19(23):7423-7436
A total synthesis of the proposed structures of fulicineroside and its aglycone fulicinerine is reported. The tetrasubstituted dibenzofuran substructure was accessible either through a Pd‐mediated ortho‐metalation or by an Ir‐catalyzed meta‐borylation. The synthesis of the β,β,α‐linked trisaccharide consisting of D ‐olivose, L ‐rhodinose, and L ‐rhamnose was challenged by the unprecedented β‐linked rhodinose. A Pd‐catalyzed β‐selective glycosylation of a 4‐epi‐rhodinose and a subsequent Mitsunobu inversion provided selectively the β‐linked L ‐rhodinose‐L ‐rhamnose disaccharide. Comparison with the reported data for the natural product and the aglycone suggests a misassignment of the structure of the natural product. 相似文献
5.
Stereoselective β‐mannosylation has been recognized as one of the greatest challenges of carbohydrate chemistry. Herein, we described a practical method for stereoselective construction of β‐mannosides by using a 2,6‐lactone‐bridged thiomannosyl donor through the remote acyl‐group participation as well as the steric effect of O‐4 substituent. The two effects are enabled through the conversion of a regular mannopyranosyl 4C1 conformation into a 2,6‐lactone bridged conformation. The lactone donor could be readily prepared in three steps on a gram scale and the β‐mannosylation proceeded smoothly with high stereoselectivity for primary, secondary and tertiary alcohol acceptors. In addition, this strategy was successfully applied to the synthesis of a naturally occurring trisaccharide. 相似文献
6.
Chiaki Yamanaka Kazuhiko Hashimoto 《Journal of polymer science. Part A, Polymer chemistry》2002,40(23):4158-4166
New polyurethanes with lactone groups in the pendants and main chains were synthesized by the polyaddition of two kinds of L ‐gulonolactone‐derived diols (2,3‐O‐isopropylidene‐L ‐gulono‐1,4‐lactone and 5,6‐O‐isopropylidene‐L ‐gulono‐1,4‐lactone) with hexamethylene diisocyanate and methyl (S)‐2,6‐diisocyanatohexanoate and by the subsequent deprotection of isopropylidene groups. They were hydrolyzed more quickly than the polyurethane derived from methyl β‐D ‐glucofuranosidurono‐6,3‐lactone in a phosphate buffer solution, the pH value of which was 8.0, at 27 °C. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 4158–4166, 2002 相似文献
7.
Daohong Liao Shaoqiang Yang Jianyu Wang Jian Zhang Benke Hong Fan Wu Prof. Dr. Xiaoguang Lei 《Angewandte Chemie (International ed. in English)》2016,55(13):4291-4295
The increase and spread of Gram‐negative bacteria that resistant are to almost all currently available β‐lactam antibiotics is a major global health problem. The primary cause for drug resistance is the acquisition of metallo‐β‐lactamases such as metallo‐β‐lactamase‐1 (NDM‐1). The fungal natural product aspergillomarasmine A (AMA), a fungal natural product, is an inhibitor of NDM‐1 and has shown promising in vivo therapeutic potential in a mouse model infected with NDM‐1‐expressing Gram‐negative bacteria. The first total synthesis and stereochemical configuration reassignment of aspergillomarasmine A is reported. The synthesis highlights a flexible route and an effective strategy to achieve the required oxidation state at a late stage. This modular route is amenable to the efficient preparation of analogues for the development of metallo‐β‐lactamase inhibitors to potentiate β‐lactam antibiotics. 相似文献
8.
Omuralide and Vibralactone: Differences in the Proteasome‐ β‐Lactone‐γ‐Lactam Binding Scaffold Alter Target Preferences 下载免费PDF全文
Dr. Nerea Gallastegui Marion Rusch Dr. Christian Hedberg Prof. Dr. Stephan A. Sieber Prof. Dr. Michael Groll 《Angewandte Chemie (International ed. in English)》2014,53(2):571-574
Despite their structural similarity, the natural products omuralide and vibralactone have different biological targets. While omuralide blocks the chymotryptic activity of the proteasome with an IC50 value of 47 nM, vibralactone does not have any effect at this protease up to a concentration of 1 mM . Activity‐based protein profiling in HeLa cells revealed that the major targets of vibralactone are APT1 and APT2. 相似文献
9.
Koichiro Ota Naoto Sugata Yoshihiko Ohshiro Dr. Etsuko Kawashima Dr. Hiroaki Miyaoka 《Chemistry (Weinheim an der Bergstrasse, Germany)》2012,18(42):13531-13537
(?)‐Hybridalactone ( 1 ) is a marine eicosanoid isolated from the red alga Laurencia hybrida. This natural product contains cyclopropane, cyclopentane, 13‐membered macrolactone and epoxide ring systems incorporating seven stereogenic centers. Moreover, this compound has an acid‐labile skipped Z,Z‐diene motif. In this paper, we report on the total synthesis of (?)‐hybridalactone ( 1 ). The unique eicosanoid (?)‐hybridalactone ( 1 ) was synthesized starting from optically active γ‐butyrolactone 2 in a linear sequence comprising 21 steps with an overall yield of 21.9 %. A key step in the synthesis of (?)‐hybridalactone ( 1 ) is the methyl phenylsulfonylacetate‐mediated one‐pot synthesis of the cis‐cyclopropane‐γ‐lactone derivative. This reaction provided an efficient and stereoselective access to cis‐cyclopropane‐γ‐lactone 12 . Further elaboration of the latter compounds through desulfonylation, epoxidation, oxidation, Wittig olefination and Shiina macrolactonization afforded (?)‐hybridalactone. 相似文献
10.
L Thijs 《Tetrahedron》2004,60(24):5237-5252
In this paper the synthesis of the natural product rubrenolide is presented. Due to an error in the original proposed stereochemical structure of rubrenolide, the synthesis was not straightforward. Application of the photo-induced rearrangement of an appropriate epoxy diazomethyl ketone gave access to the precursor lactone with an ee of 91%. Coupling of this lactone with (4S)-2,2-dimethyl-[1,3]-dioxolane-4-carbaldehyde gave, after some additional steps, the final product that was identical with an authentic sample of the natural product. 相似文献
11.
G. Jacob Boehlich Nina Schützenmeister 《Angewandte Chemie (International ed. in English)》2019,58(15):5110-5113
C‐Glycosides are carbohydrates that bear a C?C bond to an aglycon at the anomeric center. Due to their high stability towards chemical and enzymatic hydrolysis, these compounds are widely used as carbohydrate mimics in drug development. Herein, we report a general and exclusively β‐selective method for the synthesis of a naturally abundant acyl‐C‐glycosidic structural motif first found in the scleropentaside natural product family. A Corey–Seebach umpolung reaction as the key step in the synthesis of scleropentaside A and analogues enables the β‐selective construction of the anomeric C?C bond starting from unprotected carbohydrates in only four steps. The one‐pot approach is highly atom‐efficient and avoids the use of toxic heavy metals. 相似文献
12.
A formal total synthesis of the marine macrolide iriomoteolide 3a is described. Salient features of the synthesis include the elaboration of a β‐keto phosphonate derived from D ‐(?)‐tartaric acid and the extension of a chiral butyrolactone derived from L ‐glutamic acid. Ring‐closing metathesis is employed to construct the macrolactone core of the natural product. 相似文献
13.
Biology‐Oriented Synthesis of a Withanolide‐Inspired Compound Collection Reveals Novel Modulators of Hedgehog Signaling 下载免费PDF全文
Dr. Jakub Švenda Dipl.‐Biochem. Michael Sheremet M. Sc. Lea Kremer Lukáš Maier Dr. Jonathan O. Bauer Prof. Dr. Carsten Strohmann Dr. Slava Ziegler Dr. Kamal Kumar Prof. Dr. Herbert Waldmann 《Angewandte Chemie (International ed. in English)》2015,54(19):5596-5602
Biology‐oriented synthesis employs the structural information encoded in complex natural products to guide the synthesis of compound collections enriched in bioactivity. The trans‐hydrindane dehydro‐δ‐lactone motif defines the characteristic scaffold of the steroid‐like withanolides, a plant‐derived natural product class with a diverse pattern of bioactivity. A withanolide‐inspired compound collection was synthesized by making use of three key intermediates that contain this characteristic framework derivatized with different reactive functional groups. Biological evaluation of the compound collection in cell‐based assays that monitored biological signal‐transduction processes revealed a novel class of Hedgehog signaling inhibitors that target the protein Smoothened. 相似文献
14.
Kejie Zhu Sha Hu Minjie Liu Prof. Dr. Haihui Peng Prof. Dr. Fen‐Er Chen 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(29):10028-10032
A new protocol for the construction of a crucial bicyclic lactone of prostaglandins using a stereocontrolled organocatalytic Baeyer–Villiger (B‐V) oxidation was developed. The key B‐V oxidation of a racemic cyclobutanone derivative with aqueous hydrogen peroxide has enabled an early‐stage construction of a bicyclic lactone skeleton in high enantiomeric excess (up to 95 %). The generated bicyclic lactone is fully primed with two desired stereocenters and enabled the synthesis of the entire family of prostaglandins according to Corey′s route. Furthermore, the reactivity and enantioselectivity of B‐V oxidation of racemic bicyclic cyclobutanones were evaluated and 90–99 % ee was obtained, representing one of the most efficient routes to chiral lactones. This study further facilitates the synthesis of prostaglandins and chiral lactone‐containing natural products to promote drug discovery. 相似文献
15.
Steffi Rades Andreas Kornowski Prof. Dr. Horst Weller Prof. Dr. Barbara Albert 《Chemphyschem》2011,12(9):1756-1760
The reaction of lithium tetrahydridoborate and iron bromide in high boiling ether as reaction medium produces an ultrafine, pyrophoric and magnetic precipitate. X‐ray and electron diffraction proved the product to be amorphous. According to X‐ray absorption fine structure spectroscopy (XAFS) the precipitate has FeB structure up to nearly two coordination spheres around an iron absorber atom. Transmission electron microscopy (TEM) confirms the ultrafine powder to be nanoscale. Subsequent annealing at 450 °C causes the atoms to arrange in a more distinct FeB structure, and further thermal treatment to 1050 °C extends the local structure to the α‐modification of FeB. Between 1050 °C and 1500 °C α‐FeB is transformed into β‐FeB. 相似文献
16.
Tao Xie Chaoying Zheng Kuanwei Chen Haibing He Shuanhu Gao 《Angewandte Chemie (International ed. in English)》2020,59(11):4360-4364
A highly convergent approach was developed to achieve the first asymmetric and scalable total synthesis of FD‐594, a complex polycyclic xanthone natural product from Streptomyces sp. TA‐0256, in a longest linear sequence (LLS) of 20 steps. The trans‐9,10‐dihydrophenanthrene‐9,10‐diol fragment (B‐C‐D ring) was generated through a new strategy involving asymmetric dihydroxylation followed by Cu‐mediated oxidative cyclization. Late‐stage stereoselective glycosylation assembled the angular hexacyclic framework with a β‐linked 2,6‐dideoxy trisaccharide fragment. 相似文献
17.
A New Mechanism for β‐Lactamases: Class D Enzymes Degrade 1β‐Methyl Carbapenems through Lactone Formation 下载免费PDF全文
Dr. Christopher T. Lohans Emma van Groesen Kiran Kumar Catherine L. Tooke Dr. James Spencer Prof. Dr. Robert S. Paton Dr. Jürgen Brem Prof. Dr. Christopher J. Schofield 《Angewandte Chemie (International ed. in English)》2018,57(5):1282-1285
β‐Lactamases threaten the clinical use of carbapenems, which are considered antibiotics of last resort. The classical mechanism of serine carbapenemase catalysis proceeds through hydrolysis of an acyl‐enzyme intermediate. We show that class D β‐lactamases also degrade clinically used 1β‐methyl‐substituted carbapenems through the unprecedented formation of a carbapenem‐derived β‐lactone. β‐Lactone formation results from nucleophilic attack of the carbapenem hydroxyethyl side chain on the ester carbonyl of the acyl‐enzyme intermediate. The carbapenem‐derived lactone products inhibit both serine β‐lactamases (particularly class D) and metallo‐β‐lactamases. These results define a new mechanism for the class D carbapenemases, in which a hydrolytic water molecule is not required. 相似文献
18.
PMLABe Diol Synthesized by Ring‐Opening Polymerization of Racemic Benzyl β‐Malolactonate Initiated by Rare‐Earth Trisborohydride Complexes: An Experimental and DFT Study 下载免费PDF全文
Iker del Rosal Teddy Mevel Prof. Dr. Peter W. Roesky Prof. Dr. Laurent Maron Dr. Sophie M. Guillaume 《Chemistry (Weinheim an der Bergstrasse, Germany)》2014,20(44):14387-14402
Polymer diols are a class of polymeric building blocks of high interest for the synthesis of complex macromolecular edifices. Rare‐earth borohydride complexes are known as efficient initiators for the ring‐opening polymerization (ROP) of cyclic esters, directly affording α,ω‐dihydroxy‐telechelic polyesters. Here, were report the direct synthesis of poly(benzyl β‐malolactonate) (PMLABe) diols, from the ROP of racemic (benzyl β‐malolactonate) (rac‐MLABe), a valuable and renewable monomer, initiated by the homoleptic [Ln(BH4)3(thf)3] (Ln=La, Nd, and Sm) complexes. These initiators enabled the controlled ROP of this β‐lactone, affording well‐defined syndiotactic‐enriched (Pr≈0.83) PMLABes (Mn up to 21 300 g mol?1, ÐM≈1.5) as evidenced by size exclusion chromatography, 1H and 13C NMR spectroscopy, and MALDI‐ToF mass spectrometry analyses. The first and second insertions of rac‐MLABe, as assessed by DFT calculations, revealed more favorable stationary front‐side than migratory back‐side insertions, the thermodynamically and kinetically competitive ROP on two distinct arms with that on a one arm‐only, and the thermodynamically slightly favored formation of syndiotactic‐enriched PMLABes. 相似文献
19.
Tomonori Mori Dr. Shuhei Higashibayashi Dr. Taiji Goto Mitsunori Kohno Yukiko Satouchi Kazuyuki Shinko Kengo Suzuki Shunya Suzuki Hiraku Tohmiya Kimiko Hashimoto Prof. Dr. Masaya Nakata Prof. Dr. 《化学:亚洲杂志》2008,3(6):984-1012
The five practical segments for the total synthesis of siomycin A, that is, the dehydropiperidine segment A ( 5 ), the pentapeptide segment B ( 3 ), the dihydroquinoline segment C ( 6 ), and the β‐phenylselenoalanine dipeptide segments D ( 7 ) and E ( 4 ), were synthesized. Segment A ( 5 ) was constructed by the coupling of the azomethine ylide and the chiral sulfinimine, followed by the stereoselective reduction of the six‐membered imine function. Segment B ( 3 ) was synthesized by the phenylselenylation of the β‐lactone, stereoselective vinylzinc addition to the chiral sulfinimine, and oxazoline–thioamide conversion. Segment C ( 6 ) was prepared by the one‐pot olefination of the tetrahydroquinoline N‐oxide using triflic anhydride and triethylamine, stereoselective reduction of the methyl ketone function, and regioselective Yb(OTf)3‐catalyzed epoxide opening by the amino group. Segments D ( 7 ) and E ( 4 ) were synthesized by coupling of the properly protected β‐phenylselenoalanines. 相似文献
20.
Jiang MY Wang F Yang XL Fang LZ Dong ZJ Zhu HJ Liu JK 《Chemical & pharmaceutical bulletin》2008,56(9):1286-1288
Four new natural products possessing vibralactone skeleton, 1,5-secovibralactone (1), vibralactone B (2), vibralactone C (3) and acetylated vibralactone (4), together with known compound vibralactone (5), had been isolated from cultures of the basidiomycete Boreostereum vibrans. The structures of 1-4 were elucidated on the basis of spectroscopic methods. The absolute configuration of 1 was suggested to be S by computational methods. 相似文献