62777-72-4Relevant academic research and scientific papers
Sharpless epoxidation by in situ generation of furylhydroperoxides
Antonioletti,Bonadies,Lattanzi,Monteagudo,Scettri
, p. 5433 - 5436 (1992)
The compatibility of the generation of furylhydroperoxides by a radical chain process with the presence of oxygen acceptors and transition metal catalysts allows the achievement of a modified Sharpless procedure for the epoxidation of allylic alcohols and oxidation of sulphides to sulphoxides.
Total Synthesis of Kadcoccinic Acid A Trimethyl Ester
Gholami, Hadi,Trost, Barry M.,Zell, Daniel,Zhang, Guoting
supporting information, p. 12286 - 12293 (2021/08/20)
The first total synthesis of the trimethyl ester of kadcoccinic acid A is described. The central structural element of our synthesis is a cyclopentenone motif that allows the assembly of the natural product skeleton. A gold(I)-catalyzed cyclization of an enynyl acetate led to efficient construction of the cyclopentenone scaffold. In this step, optimization studies revealed that the stereochemistry of the enynyl acetate dictates regioisomeric cyclopentenone formation. The synthesis further highlights an efficient copper-mediated conjugate addition, merged with a gold(I)-catalyzed Conia-ene reaction to connect the two fragments, thereby forging the D-ring of the natural product. The synthetic strategy reported herein can provide a general platform to access the skeleton of other members of this family of natural products.
Bridgehead Modifications of Englerin A Reduce TRPC4 Activity and Intravenous Toxicity but not Cell Growth Inhibition
Wu, Zhenhua,Suppo, Jean-Simon,Tumova, Sarka,Strope, Jonathan,Bravo, Fernando,Moy, Melody,Weinstein, Ethan S.,Peer, Cody J.,Figg, William D.,Chain, William J.,Echavarren, Antonio M.,Beech, David J.,Beutler, John A.
supporting information, p. 1711 - 1716 (2020/10/19)
Modifications at the bridgehead position of englerin A were made to explore the effects of variation at this site on the molecule for biological activity, as judged by the NCI 60 screen, in which englerin A is highly potent and selective for renal cancer cells. Replacement of the isopropyl group by other, larger substituents yielded compounds which displayed excellent selectivity and potency comparable to the natural product. Selected compounds were also evaluated for their effect on the ion channel TRPC4 as well as for intravenous toxicity in mice, and these had lower potency in both assays compared to englerin A.
Enantiocomplementary Epoxidation Reactions Catalyzed by an Engineered Cofactor-Independent Non-natural Peroxygenase
Crotti, Michele,Kataja, Kim M.,Poelarends, Gerrit J.,Saravanan, Thangavelu,Xu, Guangcai
supporting information, p. 10374 - 10378 (2020/04/23)
Peroxygenases are heme-dependent enzymes that use peroxide-borne oxygen to catalyze a wide range of oxyfunctionalization reactions. Herein, we report the engineering of an unusual cofactor-independent peroxygenase based on a promiscuous tautomerase that accepts different hydroperoxides (t-BuOOH and H2O2) to accomplish enantiocomplementary epoxidations of various α,β-unsaturated aldehydes (citral and substituted cinnamaldehydes), providing access to both enantiomers of the corresponding α,β-epoxy-aldehydes. High conversions (up to 98 %), high enantioselectivity (up to 98 % ee), and good product yields (50–80 %) were achieved. The reactions likely proceed via a reactive enzyme-bound iminium ion intermediate, allowing tweaking of the enzyme's activity and selectivity by protein engineering. Our results underscore the potential of catalytic promiscuity for the engineering of new cofactor-independent oxidative enzymes.
Enantioselective Total Synthesis of Cotylenin A
Nagatani, Kotaro,Nakada, Masahisa,Osada, Ryunosuke,Sugiyama, Ryoji,Uwamori, Masahiro
supporting information, p. 5556 - 5561 (2020/04/10)
A convergent enantioselective total synthesis of cotylenin A is described. The A-ring fragment, prepared via the catalytic asymmetric intramolecular cyclopropanation developed in our laboratory, and the C-ring fragment, prepared from a known chiral compound via a modified acyl radical cyclization, were successfully assembled by the Utimoto coupling reaction. The formidable carbocyclic eight-membered ring of cotylenin A was efficiently constructed by a palladium-mediated cyclization. All the hydroxy groups in the scaffold were stereoselectively introduced, and a modified reducing reagent, Me4NBH(O2CiPr)3, has been developed. The sugar moiety fragment was prepared via three consecutive carbon-oxygen bond-forming reactions, and the glycosylation was accomplished using Wan's protocol.
Total Syntheses and Determination of Absolute Configurations of Cep-212 and Cep-210, Predicted Biosynthetic Intermediates of Tetrodotoxin Isolated from Toxic Newt
Adachi, Masaatsu,Miyasaka, Tadachika,Kudo, Yuta,Sugimoto, Keita,Yotsu-Yamashita, Mari,Nishikawa, Toshio
supporting information, p. 780 - 784 (2019/01/21)
Total syntheses of Cep-212 and Cep-210, predicted biosynthetic intermediates of tetrodotoxin isolated from the Japanese toxic newt, have been accomplished from geraniol by an intramolecular hetero Diels-Alder reaction as a key step in a highly stereoselective manner. The success of these syntheses enabled us to determine their absolute configurations by using a chiral normal-phase HPLC/MS analysis of the bis-dinitrobenzene derivative of natural Cep-212 and reference derivatives prepared from chemically synthesized enantiomers.
ENGLERIN DERIVATIVES FOR TREATMENT OF CANCER
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Paragraph 0095-0097, (2019/01/21)
Disclosed is a compound of formula (I) in which a, R1- R5 and X1 are as described herein. Also disclosed are a pharmaceutical composition containing the compound and a method of using the compound for treating cancer, such as renal cancer.
Stereochemical Determination of Tuscolid/Tuscorons and Total Synthesis of Tuscoron D and E: Insights into the Tuscolid/Tuscoron Rearrangement
G?ricke, Bj?rn,Bieber, Michelle Fernandez,Mohr, Kathrin E.,Menche, Dirk
supporting information, p. 13019 - 13023 (2019/08/30)
The stereochemistry of the structurally unique myxobacterial polyketides tuscolid/tuscorons was determined by a combination of high-field NMR studies, molecular modeling, and chemical derivatization and confirmed by a modular total synthesis of tuscorons D and E. Together with the discovery of three novel tuscorons, this study provides detailed insight into the chemically unprecedented tuscolid/tuscoron rearrangement cascade.
Borinic Acid/Halide Co-catalyzed Semipinacol Rearrangements of 2,3-Epoxy Alcohols
Tanveer, Kashif,Kim, Seung-Joon,Taylor, Mark S.
supporting information, p. 5327 - 5331 (2018/09/13)
A new mode of catalysis of the semipinacol rearrangement of 2,3-epoxy alcohols is described. In combination with a halide salt additive, diarylborinic acids promote a Type II rearrangement that occurs with net retention of configuration. This unusual stereochemical outcome is consistent with a mechanism involving regioselective ring opening of the epoxy alcohol by halide, followed by rearrangement of the resulting halohydrin-derived borinic ester. The protocol is applicable to a range of substrates, enabling ring contractions and expansions as well as stereospecific syntheses of acyclic β-hydroxycarbonyl compounds.
Total synthesis of lycopene-5,6-diol and γ-carotene-5′,6′-diol stereoisomers and their HPLC separation
Yamano, Yumiko,Nishiyama, Yuya,Aoki, Atsushi,Maoka, Takashi,Wada, Akimori
, p. 2043 - 2052 (2017/03/17)
Lycopene-5,6-diol stereoisomers (1a,b) and (2a,b) and γ-carotene-5′,6′-diol stereoisomers (3a,b) and (4a,b) were synthesized by a stepwise C15?+?C10?+?C15 double Wittig reaction strategy. The key compounds erythro(anti)-C15-dihydroxy aldehydes 17a,b and their threo(syn)-stereoisomers 23a,b were prepared via Sharpless asymmetric epoxidation of geraniol and nerol followed by acidic hydrolysis of the epoxides in a stereospecific manner. The enantiomerically enriched anti-isomers were obtained by way of recrystallization of 2,3-epoxygeranyl 3,5-dinitrobenzoates 9a,b, whereas syn-isomers were obtained as enantiomerically pure forms via recrystallization of dihydroxyneryl 3,5-dinitrobenzoates 21a,b. In order to determine the absolute stereochemistry of natural products, HPLC separation methods for each enantiomers 1a,b–4a,b were established by using a column carrying a chiral stationary phase.
