- First total synthesis of cryptosporiopsin A
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The first total synthesis of polyketide natural product cryptosporiopsin A (1) was described. It has been accomplished in 12 longest linear steps with 15.4% overall yield starting from enantiomerically pure epoxide 12 prepared by hydrolytic kinetic resolu
- Thirupathi, Barla,Mohapatra, Debendra K.
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- Rational design of resorcylic acid lactone analogues as covalent MNK1/2 kinase inhibitors by tuning the reactivity of an enamide Michael acceptor
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Recent biological and computational advances in drug design have led to renewed interest in targeted covalent inhibition as an efficient and practical approach for the development of new drugs. As part of our continuing efforts in the exploration of the t
- Xu, Jin,Chen, Anqi,Joy, Joma,Xavier, Vanessa Joanne,Ong, Esther H. Q.,Hill, Jeffrey,Chai, Christina L. L.
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- Antiproliferative and apoptotic activities of sequence-specific histone acetyltransferase inhibitors
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In parallel to monomeric epigenetic regulators, sequence-specific epigenetic regulators represent versatile synthetic dual-target ligands that achieve regulatory control over multi-gene networks. Development of DNA-binding domain (DBD)-HDAC inhibitors and DBD-HAT activators, which result in increased histone acetylation, has become one promising research field. However, there is no report regarding the gene regulatory pattern by sequence-specific epigenetic repressor. We report here for the first time, the synthesis of DBD-HAT inhibitors and demonstrate that these conjugates could retain their dual-target activity using predicted working model of thermal stability assay and in vitro HAT activity assay. Evaluation of antiproliferative activity in cancer cells showed that 2 (with a medium linker length of 13-atom) exhibited the highest antiproliferative activity in p53 wild-type cancer cell lines (IC50 of 1.8–2.6 μM in A549 and MV4-11 cells) and not in p53 mutant cancer cell lines. A mechanistic investigation using microarray analysis and an apoptotic assay showed that the antiproliferative effect of 2 occurred via the up-regulation of p53 target genes, and the subsequent initiation of p53-dependent apoptosis. Our research on sequence-specific dual-target epigenetic repressor offers us an alternative way to modulate HAT-governed therapeutically important genes and contributes to offer a fresh insight into antitumor therapeutics.
- Yu, Zutao,Taniguchi, Junichi,Wei, Yulei,Pandian, Ganesh N.,Hashiya, Kaori,Bando, Toshikazu,Sugiyama, Hiroshi
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- Lysilactones A-C, three 6H-dibenzo[b,d]pyran-6-one glycosides from Lysimachia clethroides, total synthesis of Lysilactone A
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Three 6H-dibenzo[b,d]pyran-6-one glycosides named lysilactones A-C (1-3) were isolated from the aerial parts of Lysimachia clethroides. Their structures were elucidated using spectroscopic analysis and chemical evidence. This is the first report of 6H-dib
- Liang, Dong,Luo, Huan,Liu, Yan-Fei,Hao, Zhi-You,Wang, Yan,Zhang, Chun-Lei,Zhang, Qing-Jian,Chen, Ruo-Yun,Yu, De-Quan
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- Organocatalytic Enantioselective Michael-Acetalization-Reduction-Nef Reaction for a One-Pot Entry to the Functionalized Aflatoxin System. Total Synthesis of (-)- Dihydroaflatoxin D2 and (-)- and (+)-Microminutinin
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An efficient method has been developed for the enantioselective synthesis of the aflatoxin system with multiple stereocenters via a sequence of organocatalytic Michael-acetalization-reduction-Nef reactions that proceed with high enantioselectivities (90-99% ee). The one-pot reaction sequence provides a facile entry to the aflatoxin system, including dihydroaflatoxin D2, which includes a formal total synthesis of aflatoxin B2. The first total synthesis of (-)- and (+)-microminutinin was also achieved via this protocol.
- Huang, Wei-Lun,Raja, Arun,Hong, Bor-Cherng,Lee, Gene-Hsiang
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- First Total Syntheses of Amorfrutin C and pseudo-Amorfrutin A
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Syntheses of amorfrutin C, a natural product with potent antitumor activity, as well as pseudo-amorfrutin A were accomplished. Protected 2,4-dihydroxybenzoic acid derivative 5 was used as a common synthetic intermediate. The introduction of a prenyl moiety to 5 was achieved through bromination followed by a CuCN-meditated alkylation reaction. Interestingly, N-bromosuccinimide promoted monobromination at the 6-position, leading to pseudo-amorfrutin A; 1,3-dibromo-5,5-dimethylhydantoin triggered bromination at both the 6- and 8-positions, leading to naturally occurring amorfrutin C.
- Miao, Qi,Li, Yunzhi,Xu, Jinyi,Lin, Aijun,Tanabe, Genzoh,Muraoka, Osamu,Wu, Xiaoming,Xie, Weijia
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- Synthesis and biological studies of a triazole analogue of resorcylic acid lactone LL-Z1640-2
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A highly convergent and concise synthesis of a triazole analogue of resorcylic acid lactone natural product LL-Z1640-2 has been achieved from easily accessible starting materials in six linear steps in 18% overall yield. Biological evaluationconfirmed the enone system of the natural product is crucial for its activity. The triazole analogue showed good activity (IC50 7.2 μM) against MNK2 kinase, which is an emerging target for cancer chemotherapy.
- Goh, Wendy Y. L.,Chai, Christina L. L.,Chen, Anqi
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- Structure elucidation and total synthesis of altenuic acid III and studies towards the total synthesis of altenuic acid II
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The structure of the Alternaria mycotoxin altenuic acid III was elucidated by NMR spectroscopic analysis of an authentic sample, and was confirmed by total synthesis. This compound is not a resorcylic acid lactone but a resorcylic acid substituted with a butenolide, and thus is the first member of a new class of alternaria toxins. For the total synthesis, a short and efficient access to halogenated butenolides bearing acetal-protected side-chains was carried out. Suzuki coupling of these butenolides with a highly functionalized boronate gave rise to a precursor of the natural product in high yield. The side-chain was completed by deprotection and subsequent oxidation. An unexpected cascade reaction leading to tricyclic butenolides was discovered during optimization of the deprotection protocol. Cleavage of the acetal protecting group gave altenuic acid III. Furthermore, a synthetic study towards altenuic acid II, a compound with a characteristic spirolactone structure, is described. It was planned to construct the spirocyclic lactone by using an intramolecular Michael-type addition of an aromatic carboxylate group to a butenolide moiety, but this approach was not successful. While testing the feasibility of this concept, a new and mild protocol for the well-known Pinner reaction in the presence of Lewis acids was discovered. Altenuic acid III, a major mycotoxin from Alternaria fungi, is the first member of a new class of alternaria toxins. Its structure was elucidated, and a total synthesis is given. Copyright
- Nemecek, Gregor,Thomas, Robert,Goesmann, Helmut,Feldmann, Claus,Podlech, Joachim
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- First Total Synthesis of Gaylussacin and Its Stilbene Derivatives
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Gaylussacin (1), a stilbene glucoside, has been isolated fromPentarhizidium orientaleand is used in Korean folk medicine. Although it was first isolated in 1972, the synthesis of gaylussacin has never been reported. Herein, we report the first total synth
- Song, Injae,Lim, Hyewon,Chun, Simin,Lee, Seok Beom,Huh, Jungmoo,Oh, Dong-Chan,Hong, Suckchang
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- A general modular approach for the solubility tagging of BODIPY dyes
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We describe a general and practical strategy for the direct one-step incorporation of a tunable solubility module at the boron atom of F-BODIPY dyes. The tethering reaction uses easy-to-handle reagents, has broad functional group compatibility and proceed
- Blázquez-Moraleja, Alberto,álvarez-Fernández, Delia,Prieto Montero, Ruth,García-Moreno, Inmaculada,Martínez-Martínez, Virginia,Ba?uelos, Jorge,Sáenz-de-Santa-María, Inés,Chiara, María D.,Chiara, Jose Luis
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- Total synthesis and structural revision of greensporone F and dechlorogreensporone F
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The first asymmetric total syntheses of the real isolation product (2S,5R,8R)-greensporone F and (2S,5R,8R)-dechlorogreensporone F, 14-membered resorcylic acid lactones with a cis-2,5-disubstituted tetrahydrofuran ring system, was accomplished. The synthesis features a late-stage Lewis acid-catalyzed stereoselective intramolecular oxa-Michael reaction, E-selective ring-closing metathesis, De Brabander's esterification, and Jacobsen's hydrolytic kinetic resolution as the key steps. Synthesis of both real isolation and erroneously proposed structure necessitated the revision of the absolute configuration of greensporone F and dechlorogreensporone F. The erroneous representation of (2S,5S,8S)-configuration in greensporone F and dechlorogreensporone F was assigned to be (2S,5R,8R) by comparison with the NMR data and specific rotation of the synthetic compounds with that of the reported data.
- Mohapatra, Debendra K.,Gaddam, Janardhan,Reddy, Aedula Vishnu V.,Sarma, Akella V.S.,Yadav, Jhillu S.
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- Synthetic cajaninstilbene acid derivatives eradicate methicillin-resistant Staphylococcus aureus persisters and biofilms
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The Staphylococcus aureus can switch to a transient genotype-invariant dormancy, known as a persister, to survive treatment with high doses of antibiotics. This transient persister is an important reason underlying its resistance. There is an urgent need to find new antibacterial agents capable of eradicating methicillin-resistant S. aureus (MRSA) persisters. In this study, 37 new derivatives of cajaninstilbene acid (CSA) were designed and synthesized, and their biological activity against MRSA persisters was evaluated. Most of the newly synthesized derivatives exhibit more potent antimicrobial properties against S. aureus and MRSA than CSA itself, and 23 of the 37 derivatives show a tendency to eradicate MRSA persisters. A representative compound (A6) was demonstrated to target bacterial cell membranes. It eradicated the adherent biofilm of MRSA in a concentration dependent manner, and showed a synergistic antibacterial effect with piperacilin. In a model mouse abscess caused by MRSA persisters, A6 effectively reduced the bacterial load in vivo. These results indicate that A6 is a potential candidate for treatment of MRSA persister infections.
- Yu, Jia-Hui,Xu, Xiao-Fang,Hou, Wen,Meng, Ying,Huang, Mei-Yan,Lin, Jing,Chen, Wei-Min
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- Novel Synthtic Method for gaylussacin derivatives
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The present invention relates to a novel synthetic method of genuine derivatives and the like. In particular, the synthesis procedure of the present invention can be applied to mass production through a simple synthesis procedure with simple synthesis steps, and is expected to be able to secure an amount necessary for the preclinical/clinical stage in a short time in a short time without chromatographic procedures.
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Paragraph 0172-0176
(2021/11/02)
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- Synthesis and evaluation of novel and potent protease activated receptor 4 (PAR4) antagonists based on a quinazolin-4(3H)-one scaffold
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Protease activated receptor 4 (PAR4) is an important target in antiplatelet therapy to reduce the risk of heart attack and thrombotic complications in stroke. PAR4 antagonists can prevent harmful and stable thrombus growth, while retaining initial thrombus formation, by acting on the late diffusion stage of platelet aggregation, and may provide a safer alternative to other antiplatelet agents. To date, only two PAR4 antagonists, BMS-986120 and BMS-986141 have entered clinical trials for thrombosis. Thus, the development of a potent and selective PAR4 antagonist with a novel chemotype is highly desirable. In this study, we explored the activity of quinazolin-4(3H)-one-based PAR4 antagonists, beginning with their IDT analogues. By repeated structural optimisation, we developed a series of highly selective PAR4 antagonists with nanomolar potency on human platelets. Of these, 13 and 30g, with an 8-benzo[d]thiazol-2-yl-substituted quinazolin-4(3H)-one structure, showed optimal activity (h. PAR4-AP PRP IC50 = 19.6 nM and 6.59 nM, respectively) on human platelets. Furthermore, 13 and 30g showed excellent selectivity for PAR4 versus PAR1 and other receptors (IC50s > 10 μM) on human platelets. And 13 and 30g were lack of cross-reactivity for PAR1 or PAR2 (PAR1 AP FLIPR IC50 > 3162 nM, PAR2 AP FLIPR IC50 > 1000 nM) in the calcium mobilization assays. Metabolic stability assays and cytotoxicity tests of 13 and 30g indicated that these compounds could sever as promising drug candidates for the development of novel PAR4 antagonists. In summary, the quinazolin-4(3H)-one-based analogues are the first reported chemotypes with excellent activity and selectivity against PAR4, and, in the current study, we expanded the structural diversity of PAR4 antagonists. The two compounds, 13 and 30g, found in our study could be promising starting points with great potential for further research in antiplatelet therapy.
- Kong, Yi,Li, Shanshan,Liu, Shangde,Xie, Roujie,Yuan, Duo,Zhu, Xiong
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supporting information
(2021/08/16)
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- Asymmetric total syntheses of naturally occurring α,β-enone-containing RALs, L-783290 and L-783277 through intramolecular base-mediated macrolactonization reaction
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Asymmetric total synthesis of two naturally occurring α,β-enone containing RALs, L-783290 and L-783277 is described in this article. An E-selective Horner-Wadsworth-Emmons (HWE) olefination was used as a key reaction to construct the C7′-C8′ olefinic unsaturation in L-783290. An enantiopure alkyne addition to the aldehyde followed by Z-selective partial reduction was employed to construct the C7′-C8′ olefinic unsaturation in L-783277. Biomimetic lactonization reaction was used to construct the macrolactone core in both the target molecules.
- Chakraborty, Joy,Ghosh, Ankan,Nanda, Samik
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p. 2331 - 2345
(2020/04/07)
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- Total Synthesis of (-)-Citreoisocoumarin, (-)-Citreoisocoumarinol, (-)-12-epi-Citreoisocoumarinol, and (-)-Mucorisocoumarins A and B Using a Gold(I)-Catalyzed Cyclization Strategy
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A unified and concise first asymmetric total synthesis of (-)-citreoisocoumarin (2), (-)-citreoisocoumarinol (3), 12-epi-citreoisocoumarinol (4), and (-)-mucorisocoumarins A (5) and B (6) have been accomplished from the common intermediate (-)-6-O-methyl-
- Mallampudi, N. Arjunreddy,Choudhury, Utkal Mani,Mohapatra, Debendra K.
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p. 4122 - 4129
(2020/04/10)
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- Total Synthesis and Structural Revision of Monocillin VII
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The first asymmetric total synthesis of macrolactone monocillin VII and its C-10′ epimer was achieved starting from a known chiral pure epoxide in 16 longest linear sequences. The present synthesis highlights the macrolactone formation involving an alkyne-dicobalt carbonyl complex under De Brabander's conditions followed by an unexpected regioselective hydration. The asymmetric total synthesis resulted in the revision of the configuration at C10′ and reassignment of the absolute configuration of the natural product.
- Mallampudi, N. Arjunreddy,Srinivas, Beduru,Reddy, Jithender G.,Mohapatra, Debendra K.
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supporting information
p. 5952 - 5956
(2019/08/26)
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- Asymmetric total synthesis of paecilomycin C through intramolecular nucleophilic ring opening of an epoxide
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The convergent total synthesis of naturally occurring paecilomycin C is described here for the first time. Asymmetric Brown allylation, E-selective cross metathesis, and a biomimetic carboxylate assisted intramolecular nucleophilic ring opening of an epoxide were employed to access the enantiopure γ-lactone framework of the natural product. Late stage E-selective Julia-Kocienski olefination was then employed to furnish the natural product in an efficient way.
- Chakraborty, Joy,Nanda, Samik
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supporting information
p. 7369 - 7379
(2019/08/15)
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- Total synthesis and stereochemical revision of relgro and 10′-oxorelgro
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The first asymmetric total synthesis and stereochemical assignments of 10-membered macrolactones relgro and 10′-oxorelgro are disclosed. To this end, palladium-catalyzed Stille coupling, the Mitsunobu reaction, ring-closing metathesis, EDCI promoted coupling and the Jacobsen hydrolytic kinetic resolution are used as key steps. The total synthesis followed by thorough evaluation of the optical rotation and CD spectral data led to the revision of the absolute configuration at C-6′ for both relgro and 10′-oxorelgro. Moreover, the 1H as well as 13C NMR data are reported for the first time for relgro.
- Gaddam, Janardhan,Reddy, G. Sudhakar,Marumudi, Kanakaraju,Kunwar, Ajit C.,Yadav, Jhillu S.,Mohapatra, Debendra K.
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p. 5601 - 5614
(2019/06/13)
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- Synthetic technology of natural product aAmorfrutin C with anti-cancer activity
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The invention belongs to the field of chemical synthesis, and particularly relates to a fully synthetic method of extracting a natural product 2-hydroxyl-4-methoxyl-3,5-di(3-methyl butyl-2-alkene-1-base)-6-bibenzylcarboxylic acid (Amorfrutin C) from a plant Glycyrrhiza foetida. The method comprises the step that 2,4,6-trihydroxybenzoic acid purchased commercially is subjected to multi-step reaction to synthesize the natural product 2-hydroxyl-4-methoxyl-3,5-di(3-methyl butyl-2-alkene-1-base)-6-bibenzylcarboxylic acid (Amorfrutin C) extracted from the plant Glycyrrhiza foetida.
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Paragraph 0011; 0012; 0013
(2018/10/19)
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- Electrochemical Intramolecular C—H/O—H Cross-Coupling of 2-Arylbenzoic Acids
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A synthetic protocol to lactones by electro-oxidative induced C—H activation of 2-arylbenzoic acids has been developed. By using Na2SO4 aqueous solution as a cheap and green supporting electrolyte, different 2-arylbenzoic acids could provide the corresponding lactones in 30%—90% yields. This reaction could be conducted on a gram scale with a good efficiency as well as a high utility for natural product synthesis.
- Shao, Ailong,Li, Na,Gao, Yong,Zhan, Jirui,Chiang, Chien-Wei,Lei, Aiwen
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supporting information
p. 619 - 624
(2018/05/30)
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- Synthetic process for natural product Amorfrutin C with anticancer activity
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The invention relates to the synthesis of natural products, especially to a synthetic process for the natural product Amorfrutin C with anticancer activity, belonging to the technical fields of chemical organic synthesis and pharmacy. According to the invention, the compound 2,4,6-trihydroxybenzoic acid is used as a starting material; a phenethyl side chain is introduced through a suzuki reaction;a diisopentenyl side chain is introduced through NaH-mediated [1,1]-rearrangement; altogether eight steps of reactions are carried out to complete the synthesis of Amorfrutin C, and gram-level scale-up can be realized; and a water-sensitive cyclization step in the prior art is avoiding, so a foundation is laid for the smooth realization of the full synthesis and industrial production of Amorfrutin C. A plurality of structural sites of the natural product Amorfrutin C with anticancer activity are modified in the invention; high yield is realized; and the synthetic process is suitable for pilotscale-up and subsequent industrialization, so mass chemical synthesis of the natural product and its derivatives can be realized.
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Paragraph 0020; 0034-0036
(2019/01/07)
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- Gold(I)-Catalyzed Cyclization for the Synthesis of 8-Hydroxy-3- substituted Isocoumarins: Total Synthesis of Exserolide F
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A highly regioselective gold(I)-catalyzed 6-endo-dig cyclization of 2,2-dimethyl-5-(alkynyl)-4H-benzo[d][1,3]dioxin-4-ones for the synthesis of 8-hydroxy-3-substituted isocoumarins is described. Key features of the reaction include the broad substrate scope, scalability, and tolerance for protecting groups. The synthetic utility of this novel method is demonstrated by the first total synthesis of exserolide F, an isocoumarin-containing polyol natural product.
- Mallampudi, N. Arjunreddy,Reddy, G. Sudhakar,Maity, Saurabh,Mohapatra, Debendra K.
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supporting information
p. 2074 - 2077
(2017/04/28)
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- A Short and Efficient Approach for the Total Synthesis of (S)-Zearalenone and (R)-De-O-methyllasiodiplodin by Using Stille and RCM Protocols
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A concise, flexible, and linear approach has been devised for the total synthesis of the resorcinylic acid lactones (S)-zearalenone (2) and (R)-de-O-methyllasiodiplodin (4) by using a Stille cross-coupling strategy. The other key steps of the synthesis include a ring-closing metathesis (RCM), a chemoselective reduction of an α,β-unsaturated ketone, and a transesterification reaction.
- Kumar Dey, Sujit,Ataur Rahman, Mohammad,Alkhazim Alghamdi, Ahmad,Reddy, Basi V. Subba,Yadav, Jhillu S.
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p. 1684 - 1692
(2016/04/05)
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- Stereoselective synthesis of (3R,6S)-6-hydroxylasiodiplodin
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The first stereoselective synthesis of polyketide natural product (3R,6S)-6-hydroxylasiodiplodin (1) has been described starting from commonly available starting materials d-mannitol and 2,4,6-trihydroxybenzoic acid. The key reactions involved are Keck asymmetric allylation, Stille coupling, De Brabander's esterification, and ring-closing metathesis (RCM) reaction. The total synthesis was achieved in 19.3% overall yield making the route significant.
- Bujaranipalli, Sheshurao,Das, Saibal
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supporting information
p. 1653 - 1655
(2016/04/04)
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- First stereoselective total synthesis of paecilomycin G
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The stereoselective total synthesis of resorcylic acid lactone, paecilomycin G (1) has been accomplished. The key steps involved are the Corey-Fuchs reaction, Sharpless asymmetric dihydroxylation, Jacobsen hydrolytic kinetic resolution, Stille coupling, Mitsunobu reaction, and Ring-closing metathesis (RCM) reaction.
- Bujaranipalli, Sheshurao,Das, Saibal
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supporting information
p. 2800 - 2802
(2016/06/09)
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- Carbohydrate-Based Studies Toward the Synthesis of Hamigeromycin E: A Stereoselective Total Synthesis of an Isomer of Zeaenol
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A stereoselective synthesis of 14-membered macrolide hamigeromycin E (6) has been studied by employing ortho-lithiated formylation, Barbier allylation, Julia–Kocienski olefination, Mitsunobu esterification, and ring-closing metathesis (RCM) reactions. The
- Saidachary, Gannerla,China Raju, Bhimapaka
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p. 425 - 435
(2016/07/06)
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- Modular Total Syntheses of the Marine-Derived Resorcylic Acid Lactones Cochliomycins A and B Using a Late-Stage Nozaki-Hiyama-Kishi Macrocyclization Reaction
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The natural products cochliomycin A (1) and cochliomycin B (2), two resorcylic acid lactones obtained from marine sources, have been prepared in a concise and stereocontrolled manner from the readily accessible building blocks 4-6. Olefin cross-metathesis
- Bolte, Benoit,Basutto, Jose A.,Bryan, Christopher S.,Garson, Mary J.,Banwell, Martin G.,Ward, Jas S.
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p. 460 - 470
(2015/08/11)
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- A Carbohydrate Approach for the First Total Synthesis of Cochliomycin C: Stereoselective Total Synthesis of Paecilomycin E, Paecilomycin F and 6′-epi-Cochliomycin C
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The first total synthesis of the chlorinated resorcylic acid lactone cochliomycin C is achieved starting from the readily available sugar D-lyxose. The strategy has also lead to the total synthesis of natural resorcylic acid lactones paecilomycin E, paecilomycin F and a synthetic analogue 6-epi-cochliomycin C. The key reactions include Ohira-Bestmann alkynylation, ring closing metathesis and regioselective methylation under Mitsunobu conditions. The first total synthesis of the chlorinated resorcylic acid lactone cochliomycin C is achieved starting from the readily available sugar D-lyxose. The strategy has also lead to the total synthesis of paecilomycin E, paecilomycin F and 6′-epi-cochliomycin C. The key reactions include Ohira-Bestmann alkynylation, ring closing metathesis and regioselective methylation under Mitsunobu conditions.
- Mahankali, Bakkolla,Srihari, Pabbaraja
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p. 3983 - 3993
(2015/06/30)
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- RESORCYLIC ACID LACTONE COMPOUNDS
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Disclosed are a novel resorcyclic acid lactone compound with inhibitory activity against protein kinases, a pharmaceutically acceptable salt thereof, a method for the synthesis thereof, and a pharmaceutical composition for the treatment and prevention of
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Paragraph 0075; 0076; 0077
(2014/06/23)
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- Stereoselective total synthesis of paecilomycin e
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First total synthesis of recently isolated resorcylic acid lactone paecilomycin E has been accomplished. The key reactions include olefin metathesis, Mitsunobu reaction, Stille coupling and regioselective allylation.
- Srihari,Mahankali,Rajendraprasad
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supporting information; experimental part
p. 56 - 58
(2012/01/06)
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- First total synthesis of prasinic acid and its anticancer activity
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The first total synthesis of prasinic acid is being reported along with its biological evaluation. The ten step synthesis involved readily available and cheap starting materials and can easily be transposed to large scale manufacturing. The crucial steps of the synthesis included the formation of two different aromatic units (7 and 9) and their coupling reaction. The synthetic prasinic acid exhibited moderate antitumor activity (IC50 4.3-9.1 μM) in different lines of cancer cells.
- Chakor, Narayan,Patil, Ganesh,Writer, Diana,Periyasamy, Giridharan,Sharma, Rajiv,Roychowdhury, Abhijit,Mishra, Prabhu Dutt
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supporting information
p. 6608 - 6610
(2013/01/14)
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- Revision of the structure and total synthesis of altenuisol
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A total synthesis of the reported structure of altenuisol is described. Comparison of the 1H NMR spectra of the synthesized compound and of the natural product revealed that the originally proposed structure was not correct. Consequently, two constitutional isomers were synthesized. The spectra of one of these compounds - a structure originally proposed as the structure of altertenuol - matched perfectly with the spectra of the natural product. The total synthesis of altenuisol was thus achieved starting with phloroglucinic acid and protocatechuic aldehyde in 10 steps and in 23% yield, where the longest linear sequence consisted of 6 steps. The key step was a Suzuki coupling with concomitant formation of the lactone ring. Whether altertenuol is identical with altenuisol could not be decided. Total synthesis of altenuisol, a minor toxin in ubiquitous Alternaria spp. revealed that the originally proposed structure was not correct. Altenuisol was proved to have an isomeric structure by total synthesis. Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
- Nemecek, Gregor,Cudaj, Judith,Podlech, Joachim
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scheme or table
p. 3863 - 3870
(2012/09/25)
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- Synthesis of the purported ent -pochonin J structure featuring a stereoselective oxocarbenium allylation
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The synthesis of the alleged natural product pochonin J is presented. Key steps of this convergent synthesis include a chemoselective Wacker oxidation, and an Evans anti-reduction of the resulting ketone. Upon ozonolysis, this intermediate undergoes a 6-e
- Martinez-Solorio, Dionicio,Belmore, Kenneth A.,Jennings, Michael P.
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scheme or table
p. 3898 - 3908
(2011/07/08)
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- First total syntheses of (3 R,5 R)-sonnerlactone and (3 r,5 s)-sonnerlactone
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First total syntheses of the macrocyclic natural products (3R,5R)-sonnerlactone and (3R,5S)-sonnerlactone, two new metabolites isolated from the endophytic fungus strain Zh6-B1, have been accomplished in eleven steps with 22% overall yield starting from enantiomerically pure (R)-propylene oxide prepared by hydrolytic kinetic resolution. Other key steps are Sharpless epoxidation, reductive elimination of iodo epoxide, and ring-closing-metathesis reaction for the construction of the macrolactone. Georg Thieme Verlag Stuttgart · New York.
- Thirupathi, Barla,Gundapaneni, Raghava R.,Mohapatra, Debendra K.
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scheme or table
p. 2667 - 2670
(2011/12/04)
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- Stereoselective total synthesis of (3 R,5 R)-5-hydroxy-de- O -methyllasiodiplodin via the prins cyclization
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A practical stereoselective total synthesis of (3R,5R)-5-hydroxy-de-O- methyllasiodiplodin has been accomplished via Prins cyclization. It exhibits potato microtuber inducing activity. The synthetic sequence involves Prins cyclization, reductive opening o
- Yadav, Jhillu S.,Thrimurtulu,Rahman, Md. Ataur,Reddy, J. Satyanarayana,Prasad,Reddy, B. V. Subba
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scheme or table
p. 3657 - 3662
(2010/12/19)
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- An efficient and enantioselective total synthesis of naturally occurring L-783277
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Naturally occurring L-783277 which belongs to 14-membered resorcylic acid lactones (RALs) turned out to be a potent kinase inhibitor against MEK (MAP kinase kinase). We successfully accomplished efficient and enantioselective total synthesis of L-783277 based on convergent assembly of one aromatic unit and two chiral building blocks with efficient orthogonal protection-deprotection strategy. Three key steps composed of olefin cross metathesis, addition of acetylene derivative to aldehyde, and Yamaguchi macrolactonization were subsequently employed to construct the framework of L-783277. The optical rotation value of L-783277 is for the first time presented in this Letter.
- Choi, Hwan Geun,Son, Jung Beom,Park, Dong-Sik,Ham, Young Jin,Hah, Jung-Mi,Sim, Taebo
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scheme or table
p. 4942 - 4946
(2011/01/04)
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- Total synthesis of graphislactone G
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We present a total synthesis of the fungal natural product graphislactone G, a chlorinated resorcylic lactone. The key step is a Suzuki coupling used for the construction of the central biaryl bond. Graphislactone G was prepared in 13 steps with 22% yield
- Cudaj, Judith,Podlech, Joachim
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supporting information; experimental part
p. 3092 - 3094
(2010/07/18)
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- Synthesis of a Resorcylic Acid Lactone (RAL) library using fluorous-mixture synthesis and profile of its selectivity against a panel of kinases
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A library of resorcylic acid lactones (RAL) containing a cis-enone moiety targeting kinases bearing a cysteine residue within the ATP-binding pocket was prepared using a fluorous-mixture synthesis and evaluated against a panel of 19 kinases thus providing important structure-activity trends. Two new analogues were then profiled for their selectivity against a panel of 402 kinases providing the broadest evaluation of this pharmacophores' selectivity.
- Jogireddy, Rajamalleswaramma,Dakas, Pierre-Yves,Valot, Gaelle,Barluenga, Sofia,Winssinger, Nicolas
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supporting information; experimental part
p. 11498 - 11506
(2010/05/02)
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- Total synthesis of graphislactones A, C, D, and H, of ulocladol, and of the originally proposed and revised structures of graphislactones e and F
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Graphislactones A-H and the structurally related ulocladol are highly oxygenated resorcylic lactones produced by lichens and fungi. We present total syntheses of graphislactones A, C-F, H and of ulocladol. Graphislactones E, F, and H were synthesized for the first time. The spectra of graphislactones E and F synthesized as the originally proposed structures were not in agreement with published data. Consequently, revised structures for these compounds are proposed, whose correctness is unambiguously proven by total synthesis and comparison of the spectroscopic data. Key steps in all syntheses are Suzuki couplings for the construction of the central biaryl bond and Dakin reactions to supply further hydroxy groups required in these highly oxygenated substrates. Graphislactones A, C, and H, acylated graphislac- tone D and ulocladol were prepared in 8-11 steps with 7-20% yield starting with purchasable compounds, where the longest linear sequence consists of 5-9 steps. The syntheses are thus significantly shorter than the previously published syntheses of graphislactones A-D and of ulocladol. Graphis- lactones E and F were synthesized in 8 steps, where the longest linear sequences consist of 6 and 5 steps, respectively. They were isolated as the respective acetylated compounds with 25 and 10% yield.
- Altemoeller, Martina,Gehring, Timo,Cudaj, Judith,Podlech, Joachim,Goesmann, Helmut,Feldmann, Claus,Rothenberger, Alexander
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supporting information; experimental part
p. 2130 - 2140
(2009/09/29)
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- MULTIKINASE INHIBITORS FOR USE IN THE TREATMENT OF CANCER
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The present invention provides compounds, pharmaceutical compositions and methods for the treatment of specific cancers. Such compositions may generally comprise a compound of formula (I):...................................................................
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Page/Page column 67
(2009/03/07)
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- ZEARALENONE MACROLIDE DERIVATIVES AND USES OF THE SAME
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The present invention provides compounds, pharmaceutical compositions and methods for the treatment of specific cancers. Such compositions may generally comprise a compound of formula (I) wherein R3-R6, R8-R10,
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Page/Page column 37
(2009/03/07)
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- First chemical synthesis of three natural depsides involved in flavonol catabolism and related to quercetinase catalysis
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We report here the first chemical synthesis of three depsides related to quercetinase-catalyzed degradation of kaempferol, quercetin, and myricetin. The three depsides were constructed through the coupling of suitably protected phloroglucinol carboxylic acid and hydroxy-perbenzylated, derivatives of gallic, protocatechuic, and 4-hydroxy benzoic acids. The three synthesized target compounds proved to be identical to their natural counterparts, arising from quercetinase action on corresponding flavonols. Copyright Taylor & Francis Group, LLC.
- Tranchimand, Sylvain,Tron, Thierry,Gaudin, Christian,Iacazio, Gilles
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p. 587 - 597
(2007/10/03)
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- Synthesis of resorcinylic macrocycles related to radicicol via ring-closing metathesis
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Novel resorcinylic macrolides, for example, 17, 24, were prepared via ring-closing metathesis as analogues of the HSP90 inhibitor radicicol.
- Cooper, Tracey S.,Atrash, Butrus,Sheldrake, Peter,Workman, Paul,McDonald, Edward
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p. 2241 - 2243
(2007/10/03)
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- Total synthesis of dehydroaltenusin
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The first total synthesis of dehydroaltenusin, a natural enzyme inhibitor, is described. The key step involves Suzuki-coupling reaction of an aryl triflate prepared from 2,4,6-trihydroxybenzoic acid with a catechol-derived boronic acid or boronic ester. T
- Kamisuki, Shinji,Takahashi, Shunya,Mizushina, Yoshiyuki,Hanashima, Shinya,Kuramochi, Kouji,Kobayashi, Susumu,Sakaguchi, Kengo,Nakata, Tadashi,Sugawara, Fumio
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p. 5695 - 5700
(2007/10/03)
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- Synthesis of inhibitors of calmodulin-mediated enzymes including KS-501, KS-502 and their enantiomers
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The total synthesis of a group of compounds with inhibitory effects on calmodulin-mediated enzyme activities has been accomplished. Among these synthesized compounds are KS-501 and KS-502. Other compounds that have been synthesized by the described scheme are ent-KS-501 and ent-KS-502 which are enantiomers of KS-501 and KS-502 and which also have inhibitory effects on calmodulin-mediated enzyme activities.
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