- Squaramide-Linked Chloramphenicol Base Hybrid Catalysts for the Asymmetric Michael Addition of 2,3-Dihydrobenzofuran-2-carboxylates to Nitroolefins
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An array of hybrid catalysts incorporating a chloramphenicol base moiety linked to another chiral scaffold through a squaramide linker were developed and successfully used in the Michael addition of 2,3-dihydrobenzofuran-2-carboxylates to nitroolefins. Control experiments suggested that the hybrid catalysts were more reactive than nonhybridized bifunctional catalysts, and matching of the chirality between the two scaffolds was crucial for high reactivity and stereoselectivity. These hybrid organocatalysts could be used with a variety of substrates. At a 0.5 mol-% catalyst loading, a range of 2,3-dihydrobenzofuran-2-carboxylates derivatives bearing quaternary and tertiary stereogenic centers were obtained in high yields (up to 98 %) with excellent enantioselectivities (up to 99 % ee) and moderate diastereoselectivities (up to 8:92 dr).
- Yan, Linjie,Huang, Guanxin,Wang, Haifeng,Xiong, Fangjun,Peng, Haihui,Chen, Fener
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supporting information
p. 99 - 103
(2018/01/17)
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- Double bond formation based on nitroaldol reaction and radical elimination: A prototype segment connection method for the total synthesis of nigricanoside A dimethyl ester
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During the course of our studies toward the total synthesis of nigricanoside A dimethyl ester, a prototype method for the connection of the left- and right-half segments at the C9′–C10′ double bond was developed using a model system. The method was based
- Tsunoda, Takayuki,Fujiwara, Kenshu,Okamoto, Satoshi,Kondo, Yoshihiko,Akiba, Uichi,Ishigaki, Yusuke,Katoono, Ryo,Suzuki, Takanori
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supporting information
p. 1846 - 1850
(2018/04/11)
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- Direct aziridination of nitroalkenes affording N-alkyl-C-nitroaziridines and the subsequent Lewis acid mediated isomerization to β-nitroenamines
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A mild and highly diastereoselective one-pot synthesis of trans-N-alkyl-C-nitroaziridines was achieved by treatment of nitroalkenes with aliphatic amines and N-chlorosuccinimide. Treatment of the obtained aziridines with a Lewis acid resulted in a facile ring opening reaction, accompanied by rearrangement and isomerization into functionalized (Z)-β-nitroenamines.
- Hao, Feiyue,Asahara, Haruyasu,Nishiwaki, Nagatoshi
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supporting information
p. 5442 - 5445
(2017/11/06)
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- Oxidative Amidation of Nitroalkanes with Amine Nucleophiles using Molecular Oxygen and Iodine
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The formation of amides and peptides often necessitates powerful yet mild reagent systems. The reagents used, however, are often expensive and highly elaborate. New atom-economical and practical methods that achieve such goals are highly desirable. Ideally, the methods should start with substrates that are readily available in both chiral and non-chiral forms and utilize cheap reagents that are compatible with a wide variety of functional groups, steric encumberance, and epimerizable stereocenters. A direct oxidative method was developed to form amide and peptide bonds between amines and primary nitroalkanes simply by using I2 and K2CO3 under O2. Contrary to expectations, a 1:1 halogen-bonded complex forms between the iodonium source and the amine, which reacts with nitronates to form α-iodo nitroalkanes as precursors to the amides.
- Li, Jing,Lear, Martin J.,Kawamoto, Yuya,Umemiya, Shigenobu,Wong, Alice R.,Kwon, Eunsang,Sato, Itaru,Hayashi, Yujiro
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supporting information
p. 12986 - 12990
(2015/11/02)
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- Asymmetric Hydroazidation of Nitroalkenes Promoted by a Secondary Amine-Thiourea Catalyst
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Chiral β-nitro azides are obtained by asymmetric addition of azides to nitroalkenes, with an enantioselectivity of up to 82% ee. The reaction, promoted by an easily accessible secondary amine-thiourea catalyst, is performed with azidotrimethylsilane in th
- Bellavista, Tiziana,Meninno, Sara,Lattanzi, Alessandra,Della Sala, Giorgio
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p. 3365 - 3373
(2015/11/03)
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- Structure-based design and synthesis of antiparasitic pyrrolopyrimidines targeting pteridine reductase 1
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The treatment of Human African trypanosomiasis remains a major unmet health need in sub-Saharan Africa. Approaches involving new molecular targets are important; pteridine reductase 1 (PTR1), an enzyme that reduces dihydrobiopterin in Trypanosoma spp., has been identified as a candidate target, and it has been shown previously that substituted pyrrolo[2,3-d]pyrimidines are inhibitors of PTR1 from Trypanosoma brucei (J. Med. Chem. 2010, 53, 221-229). In this study, 61 new pyrrolo[2,3-d]pyrimidines have been prepared, designed with input from new crystal structures of 23 of these compounds complexed with PTR1, and evaluated in screens for enzyme inhibitory activity against PTR1 and in vitro antitrypanosomal activity. Eight compounds were sufficiently active in both screens to take forward to in vivo evaluation. Thus, although evidence for trypanocidal activity in a stage I disease model in mice was obtained, the compounds were too toxic to mice for further development.
- Khalaf, Abedawn I.,Huggan, Judith K.,Suckling, Colin J.,Gibson, Colin L.,Stewart, Kirsten,Giordani, Federica,Barrett, Michael P.,Wong, Pui Ee,Barrack, Keri L.,Hunter, William N.
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supporting information
p. 6479 - 6494
(2014/10/16)
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- 1,4-addition of TMSCCl3 to nitroalkenes: Efficient reaction conditions and mechanistic understanding
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Improved synthetic conditions allow preparation of TMSCCl3 in good yield (70 %) and excellent purity. Compounds of the type NBu4X [X=Ph3SiF2 (TBAT), F (tetrabutylammonium fluoride, TBAF), OAc, Cl and Br] act as catalytic promoters for 1,4-additions to a range of cyclic and acyclic nitroalkenes, in THF at 0-25 °C, typically in moderate to excellent yields (37-95 %). TBAT is the most effective promoter and bromide the least effective. Multinuclear NMR studies (1H, 19F, 13C and 29Si) under anaerobic conditions indicate that addition of TMSCCl3 to TBAT (both 0.13 M) at -20 °C, in the absence of nitroalkene, leads immediately to mixtures of Me3SiF, Ph3SiF and NBu4CCl3. The latter is stable to at least 0 °C and does not add nitroalkene from -20 to 0 °C, even after extended periods. Nitroalkene, in the presence of TMSCCl3 (both 0.13 M at -20 °C), when treated with TBAT, leads to immediate formation of the 1,4-addition product, suggesting the reaction proceeds via a transient [Me 3Si(alkene)CCl3] species, in which (alkene) indicates an Si O coordinated nitroalkene. The anaerobic catalytic chain is propagated through the kinetic nitronate anion resulting from 1,4 CCl3 - addition to the nitroalkene. This is demonstrated by the fact that isolated NBu4[CH2=NO2] is an efficient promoter. Use of H2C=CH(CH2)2CH=CHNO 2 in air affords radical-derived bicyclic products arising from aerobic oxidation. Understanding TMSCCl3: The synthesis and reactivity of TMSCCl3 has been investigated. The mechanism of 1,4-CCl3 addition to nitroalkenes begins with nitroalkene coordination, followed by the attack of an external fluoride ion, and does not involve the formation of NBu4[Me3SiFCCl3] (see figure).
- Wu, Na,Wahl, Benoit,Woodward, Simon,Lewis, William
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p. 7718 - 7724
(2014/07/07)
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- Enantioselective nickel-catalyzed michael additions of 2-acetylazaarenes to nitroalkenes
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2-Acetylazaarenes undergo catalytic enantioselective Michael additions to nitroalkenes in the presence of a chiral Ni(II)-bis(oxazoline) complex. The process is tolerant of a range of azines or azoles in the pronucleophilic component, resulting in Michael products in moderate to high enantioselectivities.
- Simpson, Alain J.,Lam, Hon Wai
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supporting information
p. 2586 - 2589
(2013/07/26)
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- Efficient and stereoselective nitration of mono- and disubstituted olefins with AgNO2 and TEMPO
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Nitroolefin is a common and versatile reagent. Its synthesis from olefin is generally limited by the formation of mixture of cis and trans compounds. Here we report that silver nitrite (AgNO2) along with TEMPO can promote the regio- and stereoselective nitration of a broad range of olefins. This work discloses a new and efficient approach wherein starting from olefin, nitroalkane radical formation and subsequent transformations lead to the desired nitroolefin in a stereoselective manner.
- Maity, Soham,Manna, Srimanta,Rana, Sujoy,Naveen, Togati,Mallick, Arijit,Maiti, Debabrata
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supporting information
p. 3355 - 3358
(2013/04/10)
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- Structure-based design of pteridine reductase inhibitors targeting African sleeping sickness and the leishmaniases
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Pteridine reductase (PTR1) is a target for drug development against Trypanosoma and Leishmania species, parasites that cause serious tropical diseases and for which therapies are inadequate. We adopted a structure-based approach to the design of novel PTR1 inhibitors based on three molecular scaffolds. A series of compounds, most newly synthesized, were identified as inhibitors with PTR1-species specific properties explained by structural differences between the T. brucei and L. major enzymes. The most potent inhibitors target T. brucei PTR1, and two compounds displayed antiparasite activity against the bloodstreamformof the parasite. PTR1 contributes to antifolate drug resistance by providing amolecular bypass of dihydrofolate reductase(DHFR) inhibition.Therefore, combining PTR1 andDHFRinhibitors might improve therapeutic efficacy. We tested two new compounds with known DHFR inhibitors. A synergistic effect was observed for one particular combination highlighting the potential of such an approach for treatment of African sleeping sickness.
- Tulloch, Lindsay B.,Martini, Viviane P.,Iulek, Jorge,Huggan, Judith K.,Lee, Jeong Hwan,Gibson, Colin L.,Smith, Terry K.,Suckling, Colin J.,Hunter, William N.
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experimental part
p. 221 - 229
(2010/05/19)
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- Practical synthesis and evaluation of the biological activities of 1α,25-dihydroxyvitamin D3 antagonists, 1α,25- dihydroxyvitamin D3-26,23-lactams. Designed on the basis of the helix 12-folding inhibition hypothesis
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A practical synthetic route to novel vitamin D antagonists of DLAM (1α,25-dihydroxyvitamin D3-26,23-lactam) was developed from vitamin D2 via the 1,3-dipolar cycloaddition reaction as a key step. Six DLAM derivatives (24 compounds) w
- Nakano, Yusuke,Kato, Yuko,Imai, Keisuke,Ochiai, Eiji,Namekawa, Jun-Ichi,Ishizuka, Seiichi,Takenouchi, Kazuya,Tanatani, Aya,Hashimoto, Yuichi,Nagasawa, Kazuo
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p. 2398 - 2406
(2007/10/03)
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- Vitamin D3 lactam derivative
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Compounds expressed by the following formula (1) or pharmaceutically permissible solvate thereof which is effective for treating Paget's disease of bone, hypercalcemia or osteoporosis. In the formula, R1 is a C2-C10 alkyl
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Page/Page column 6
(2008/06/13)
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- A New and Efficient Synthesis of Pyrrolo[2,3-d]pyrimidine Anticancer Agents: Alimta (LY231514, MTA), Homo-Alimta, TNP-351, and Some Aryl 5-Substituted Pyrrolo[2,3-d]pyrimidines
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Alimta, as well as homo-Alimta, a nonbridged analogue of Alimta, and TNP-351 have been prepared by a new method that involves Michael addition of the appropriate 1-nitroalkene with 2,6-diamino-3H-pyrimidin-4-one or 2,4,6-triaminopyrimidine, followed by a Nef reaction of the resulting primary nitro Michael adduct. Spontaneous intramolecular cyclization of the resulting aldehyde with the pyrimidine 6-amino group yields the corresponding pyrrolo[2,3-d]pyrimidine. A series of previously unknown 5-arylpyrrolo[2,3-d]pyrimidines was prepared by the same methodology from the above pyrimidines and nitrostyrenes. It has been found that the intermediate primary nitro Michael adduct can be prepared in a single step by sonication of a mixture of an arylaldehyde, nitromethane, and the 6-aminopyrimidine in acetic acid containing ammonium acetate.
- Taylor, Edward C.,Liu, Bin
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p. 9938 - 9947
(2007/10/03)
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- Process for the preparation of pyrrolo[2,3-d]pyrimidines
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4(3H)-X-7H-Pyrrolo[2,3-d]pyrimidines in which X is =O or =NH are prepared by treating a 6-amino-4(3H)-X-pyrimidine with a unsubstituted or substituted 1-nitroalk-1-ene to yield a 6-amino-4(3H)-X-pyrimidine which is substituted in the 5-position by a 1-nitroalk-2-yl group; (ii) converting the 5-(1-nitroalk-2-yl)-6-amino-4(3H)-X-pyrimidine to the corresponding 5-(1-oxoalk-2-yl)-6-amino-4(3H)-X-pyr-imidine; and (iii) removing the elements of water from the 5-(1-oxoalk-2-yl)-6-amino-4(3H)-X-pyrimidine to effect cyclization. A typical embodiment involves treating 2,6-diamino-4(3H)-pyrimidone with 1-nitro-4-(4-ethoxycarbonylphenyl)-1-butene to yield 1 -nitro-2-(2,6-diamino-4(3H)-oxopyrimidin-5-yl)-4-(4-ethoxy-carbonylphenyl)butane which is then treated sequentially with base and acid, without isolation of the intermediate aldehyde, to form 4-[2-(2-amino-4(3H)-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoic acid, a valuable known chemical intermediate for the preparation of N-[4-{2-(2-hydroxy-4-amino-7H-pyrrolo[2,3-d]-pyrimidin-5-yl)ethyl}benzoyl]glutamic acid.
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- One-pot synthesis of nitroolefins using zeolite
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Nitroolefins, versatile intermediates in organic synthesis, are conveniently prepared in yields by nitration of olefins using nitric oxide and zeolite as described.
- Sreekumar,Padmakumar, Raghavakaimal,Rugmini
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p. 2695 - 2696
(2007/10/03)
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- Convenient and Simple Preparation of Nitroolefins Nitration of Olefins with Nitric Oxide
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Nitroolefins are conveniently prepared in high yields by nitration of olefins under an atmospheric pressure of nitric oxide at room temperature and subsequent treatment with acidic alumina.
- Mukaiyama, Teruaki,Hata, Eiichiro,Yamada, Tohru
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p. 505 - 506
(2007/10/03)
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- A Convenient Method for the Preparation of Nitro Olefins by Nitration of Olefins with Nitrogen Monoxide
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Olefins with a terminal double bond or conjugated with aromatic nucleus are successfully nitrated into nitro olefins in good-to-high yields on treatment with nitrogen monoxide (NO) in 1,2-dichloroethane.Nitro alcohols formed as by-products are dehydrated to yield nitro olefins by the subsequent treatment with acidic activated alumina.By GC analysis, it was confirmed that an equimolar amount of nitro gas was evolved during the present nitration.A possible reaction pathway including the formation of nitro nitroso compounds, key intermediates, is described.The key intermediates are transformed into nitro olefins by reaction with nitrogen monoxide.
- Hata, Eiichiro,Yamada, Tohru,Mukaiyama, Teruaki
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p. 3629 - 3636
(2007/10/03)
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- An Effective and Selective Conjugate Propargylation Reaction of Stannylallenes to α,β-Unsaturated Carbonyl Compounds and α-Nitro Olefins
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Stannylallenes (1) reacted with α,β-unsaturated carbonyl compounds and α-nitro olefins in the presence of TiCl4 to give the corresponding conjugate propargylation products.Thus, the reaction of 1 with cyclic and acyclic α,β-unsaturated carbonyl compounds (2) gave β-propargylic ketones (3) in high yields.With α-nitro olefins (4), two types of products, β-propargylic nitroalkanes (5) and α-propargylic ketones (6), were obtained selectively depending on the presence or absence of the α-substituent of 4.Transformation of the products (6) to cyclopentenone derivatives (10 and 12) are also described.
- Haruta, Jun-ichi,Nishi, Koichi,Matsuda, Satoshi,Akai, Shuji,Tamura, Yasumitsu,Kita, Yasuyuki
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p. 4853 - 4859
(2007/10/02)
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