共查询到20条相似文献,搜索用时 15 毫秒
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Dr. Azusa Kondoh Dipl.‐Chem. Alexander Arlt Barbara Gabor Prof. Alois Fürstner 《Chemistry (Weinheim an der Bergstrasse, Germany)》2013,19(24):7731-7738
The lichen‐derived glycoconjugate gobienine A is structurally more complex than most glycolipids isolated from higher plants by virtue of the all‐cis substituted γ‐lactone substructure embedded into its macrocyclic frame. A concise entry into this very epimerization‐prone and hence challenging structural motif is presented, which relies on an enantioselective cyanohydrin formation, an intramolecular Blaise reaction, a palladium‐catalyzed alkoxycarbonylation, and a diastereoselective hydrogenation of the tetrasubstituted alkene in the resulting butenolide. This strategy, in combination with ring‐closing olefin metathesis for the formation of the macrocyclic perimeter, allowed the proposed structure of gobienine A ( 1 ) to be formed in high overall yield. The recorded spectral data show that the structure originally attributed to gobienine A is incorrect and that it is not the epimerization‐prone ester site on the butanolide ring that is the locus of misassignment; rather, the discrepancy must be more profound. 相似文献
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Felix Ungeheuer Prof. Alois Fürstner 《Chemistry (Weinheim an der Bergstrasse, Germany)》2015,21(32):11387-11392
An expeditious route to the potential immunosuppressive lead compound ivorenolide B ( 1 ) is described, which relies on the formation of the distinctive 1,3‐diyne subunit embedded into the 17‐membered framework of this target by ring‐closing alkyne metathesis (RCAM). This key transformation was accomplished with the aid of the molybdenum alkylidyne complex 7 , which turned out to be compatible with the acid sensitive propargylic alcohol substituents as well as the terminal alkyne unit present in the cyclization precursor. As the presence of such functionality had been detrimental for alkyne metathesis until very recently, this example illustrates the excellent application profile of this new catalyst as well as the rapidly increasing scope of the transformation. Its structural outreach can be further increased by subjecting cyclo‐1,3‐diynes to appropriate post‐metathetic transformations, most notably with the help of alkynophilic gold or palladium catalysts. This aspect is illustrated by the conversion of the model compound 4 into various cyclophane products. 相似文献
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《Chemistry (Weinheim an der Bergstrasse, Germany)》2009,15(24):5956-5968
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Prof. Dr. Masaki Kita Hirotaka Oka Akihiro Usui Tomoya Ishitsuka Dr. Yuzo Mogi Hidekazu Watanabe Masaki Tsunoda Prof. Dr. Hideo Kigoshi 《Angewandte Chemie (International ed. in English)》2015,54(47):14174-14178
An asymmetric total synthesis of the trisoxazole marine macrolides mycalolides A and B is described. This synthesis involves the convergent assembly of highly functionalized C1–C19 trisoxazole and C20–C35 side‐chain segments through the use of olefin metathesis and esterification as well as Julia–Kocienski olefination and enamide formation as key steps. 相似文献
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Dr. Shu Xu Daisuke Unabara Prof. Dr. Daisuke Uemura Prof. Dr. Hirokazu Arimoto 《化学:亚洲杂志》2014,9(1):367-375
The enantioselective total synthesis of the bioactive marine natural products pinnaic acid and halichlorine is reported in detail. Our total synthesis features the construction of the five‐membered ring and C9 and C13 stereogenic centers through a palladium‐catalyzed trimethylenemethane [3+2] cyclization; the installation of the nitrogen atom through a regioselective Beckmann rearrangement of a poorly reactive ketone; the stereoselective cyclization of the spiro ring through a four‐step, one‐pot hydrogenation–cyclization; and efficient connection of the sterically hindered lower chain through a reduced‐pressure cross olefin metathesis reaction. 相似文献
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Lian‐Dong Guo Xiong‐Zhi Huang Shi‐Peng Luo Wen‐Sen Cao Prof. Yuan‐Ping Ruan Dr. Jian‐Liang Ye Prof. Dr. Pei‐Qiang Huang 《Angewandte Chemie (International ed. in English)》2016,55(12):4064-4068
The first total synthesis of the alkaloid (?)‐haliclonin A is reported. The asymmetric synthesis relied on a novel organocatalytic asymmetric conjugate addition of nitromethane with 3‐alkenyl cyclohex‐2‐enone to set the stereochemistry of the all‐carbon quaternary stereogenic center. The synthesis also features a Pd‐promoted cyclization to form the 3‐azabicyclo[3,3,1]nonane core, a SmI2‐mediated intermolecular reductive coupling of enone with aldehyde to form the requisite secondary chiral alcohol, ring‐closing alkene and alkyne metathesis reactions to build the two aza‐macrocyclic ring systems, and an unprecedented direct transformation of enol into enone. 相似文献
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Keisuke Sakurai Prof. Dr. Makoto Sasaki Prof. Dr. Haruhiko Fuwa 《Angewandte Chemie (International ed. in English)》2018,57(18):5143-5146
Total synthesis of (?)‐enigmazole A, a marine macrolide natural product with cytotoxic activity, has been accomplished. The tetrahydropyran moiety was constructed by means of a domino olefin cross‐metathesis/intramolecular oxa‐Michael addition of a δ‐hydroxy olefin. After coupling of advanced intermediates, the macrocycle was formed through gold‐catalyzed rearrangement of a propargylic benzoate, followed by ring‐closing metathesis of the resultant α,β‐unsaturated ketone. 相似文献
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Total Synthesis,Stereochemical Revision,and Biological Reassessment of Mandelalide A: Chemical Mimicry of Intrafamily Relationships
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Dr. Jens Willwacher Dipl.‐Ing. Berit Heggen Conny Wirtz Prof. Walter Thiel Prof. Alois Fürstner 《Chemistry (Weinheim an der Bergstrasse, Germany)》2015,21(29):10416-10430
Mandelalide A and three congeners had recently been isolated as the supposedly highly cytotoxic principles of an ascidian collected off the South African coastline. Since these compounds are hardly available from the natural source, a concise synthesis route was developed, targeting structure 1 as the purported representation of mandelalide A. The sequence involves an iridium‐catalyzed two‐directional Krische allylation and a cobalt‐catalyzed carbonylative epoxide opening as entry points for the preparation of the major building blocks. The final stages feature the first implementation of terminal acetylene metathesis into natural product total synthesis, which is remarkable in that this class of substrates had been beyond the reach of alkyne metathesis for decades. Synthetic 1 , however, proved not to be identical with the natural product. In an attempt to clarify this issue, NMR spectra were simulated for 20 conceivable diastereomers by using DFT followed by DP4 analysis; however, this did not provide a reliable assignment either. The puzzle was ultimately solved by the preparation of three diastereomers, of which compound 6 proved identical with mandelalide A in all analytical and spectroscopic regards. As the entire “northern sector” about the tetrahydrofuran ring in 6 shows the opposite configuration of what had originally been assigned, it is highly likely that the stereostructures of the sister compounds mandelalides B–D must be corrected analogously; we propose that these natural products are accurately represented by structures 68 – 70 . In an attempt to prove this reassignment, an entry into mandelalides C and D was sought by subjecting an advanced intermediate of the synthesis of 6 to a largely unprecedented intramolecular Morita–Baylis–Hillman reaction, which furnished the γ‐lactone derivative 74 as a mixture of diastereomers. Whereas (24R)‐ 74 was amenable to a hydroxyl‐directed dihydroxylation by using OsO4/TMEDA as the reagent, the sister compound (24S)‐ 74 did not follow a directed path but simply obeyed Kishi’s rule; only this unexpected escape precluded the preparation of mandelalides C and D by this route. A combined spectroscopic and computational (DFT) study showed that the reasons for this strikingly different behavior of the two diastereomers of 74 are rooted in their conformational peculiarities. This aspect apart, our results show that the OsO4/TMEDA complex reacts preferentially with electron deficient double bonds even if other alkenes are present that are more electron rich and less encumbered. Finally, in a brief biological survey authentic mandelalide A ( 6 ) was found to exhibit appreciable cytotoxicity only against one out of three tested human cancer cell lines and all synthetic congeners were hardly active. No significant fungicidal properties were observed. 相似文献
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Enantioselective Total Synthesis of Terreumols A and C from the Mushroom Tricholoma terreum
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M. Sc. Alex Frichert Prof. Dr. Peter G. Jones Prof. Dr. Thomas Lindel 《Angewandte Chemie (International ed. in English)》2016,55(8):2916-2919
The cytotoxic meroterpenoids terreumol A and C from the grey knight mushroom Tricholoma terreum were synthesized for the first time. The key step of the enantioselective total synthesis of terreumol C is a ring‐closing metathesis to form a trisubstituted Z double bond embedded in the 10‐membered ring of the [8.4.0] bicycle. Interestingly, the presence of a free hydroxy group in the metathesis precursor prevents cyclization and favors cross metathesis. (?)‐Terreumol C was converted into (?)‐terreumol A by diastereoselective epoxidation. Starting from 2‐bromo‐3,5‐dimethoxybenzaldehyde, 14 steps with an overall yield of 23 % are needed for the synthesis of (?)‐terreumol A. X‐ray analysis of the benzoquinone analogue of terreumol A provides independent proof of the absolute configuration. 相似文献
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Haruaki Kurasaki Iwao Okamoto Dr. Nobuyoshi Morita Dr. Osamu Tamura Prof. Dr. 《Chemistry (Weinheim an der Bergstrasse, Germany)》2009,15(46):12754-12763
This article describes in detail the first total synthesis of grandisine alkaloids, grandisines B, D, and F, which show affinity for the human δ‐opioid receptor. The key steps in this synthesis are construction of the isoquinuclidinone moiety of 2 by intramolecular imine formation and the tetracyclic ring system of 4 by stereoselective ring closure of the enolate of amine 8 generated by 1,4‐addition of ammonia to 9 . Synthesis of key intermediate 9 featured a highly stereoselective Brønsted acid mediated Morita–Baylis–Hillman (MBH) reaction via the N‐acyl iminium ion. 相似文献
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Dipl.‐Chem. Jens Willwacher Prof. Alois Fürstner 《Angewandte Chemie (International ed. in English)》2014,53(16):4217-4221
A concise synthesis of the putative structure assigned to the highly cytotoxic marine macrolide mandelalide A ( 1 ) is disclosed. Specifically, an iridium‐catalyzed two‐directional Krische allylation and a cobalt‐catalyzed carbonylative epoxide opening served as convenient entry points for the preparation of the major building blocks. The final stages feature the first implementation of terminal‐acetylene metathesis into natural product synthesis, which is remarkable as this class of substrates was beyond reach until very recently; key to success was the use of the highly selective molybdenum alkylidyne complex 42 as the catalyst. Although the constitution and stereochemistry of the synthetic samples are unambiguous, the spectra of 1 as well as of 11‐epi‐ 1 deviate from those of the natural product, which implies a subtle but deep‐seated error in the original structure assignment. 相似文献
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Total synthesis of the polyhydroxy caprolactam amide natural product, bengamide E, is accomplished starting from tartaric acid. Key reactions in the synthesis include desymmetrization of the bis(dimethylamide) unit of tartaric acid, Zn(BH4)2‐mediated anti‐selective reduction, and a Horner–Wadsworth–Emmons olefination. 相似文献
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Prof. Dr. K. C. Nicolaou Dr. Lei Shi Dr. Min Lu Dr. Manas R. Pattanayak Dr. Akshay A. Shah Dr. Heraklidia A. Ioannidou Dr. Manjunath Lamani 《Angewandte Chemie (International ed. in English)》2014,53(41):10970-10974
The total synthesis of cytotoxic polyketides myceliothermophins E ( 1 ), C ( 2 ), and D ( 3 ) through a cascade‐based cyclization to form the trans‐fused decalin system is described. The convergent synthesis delivered all three natural products through late‐stage divergence and facilitated unambiguous C21 structural assignments for 2 and 3 through X‐ray crystallographic analysis, which revealed an interesting dimeric structure between its enantiomeric forms. 相似文献