- Synthesis of Aminomethylene- gem-bisphosphonates Containing an Aziridine Motif: Studies of the Reaction Scope and Insight into the Mechanism
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A broad range of N-carbamoylaziridines were obtained and then treated by the diethyl phosphonate anion to afford α-methylene-gem-bisphosphonate aziridines. Study of the reaction's scope and additional experiments indicates that the transformation proceeds via a new mechanism involving the chelation of lithium ion. This last step is crucial for the reaction to occur and disfavors the aziridine ring-opening. A phosphonate-phosphate rearrangement from a α-hydroxybisphosphonate aziridine intermediate is also proposed for the first time. This reaction provides a simple and convenient method for the synthesis of a highly functionalized phosphonylated aziridine motif.
- Cheviet, Thomas,Peyrottes, Suzanne
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supporting information
p. 3107 - 3119
(2021/02/05)
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- N-[4-phenyl-3-(benzoylamino)-1,1,1-trifluoro-butyl-2-yl]-phenylalaninol derivative as well as preparation method and application thereof
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The present invention discloses an N-[4-phenyl-3-(benzoylamino)-1,1,1-trifluoro-butyl-2-yl]-phenylalaninol derivative, which is a compound represented by a general formula I and a pharmaceutically acceptable salt or hydrate thereof, and wherein R1 and R3
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Paragraph 0051-0052; 0093-0096
(2020/11/23)
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- Staudinger/aza-Wittig reaction to access Nβ-protected amino alkyl isothiocyanates
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A unified approach to access Nβ-protected amino alkyl isothiocyanates using Nβ-protected amino alkyl azides through a general strategy of Staudinger/aza-Wittig reaction is described. The type of protocol used to access isothiocyanates depends on the availability of precursors and also, especially in the amino acid chemistry, on the behavior of other labile groups towards the reagents used in the protocols; fortunately, we were not concerned about both these factors as precursor-azides were prepared easily by standard protocols, and the present protocol can pave the way for accessing title compounds without affecting Boc, Cbz and Fmoc protecting groups, and benzyl and tertiary butyl groups in the side chains. The present strategy eliminates the need for the use of amines to obtain title compounds and thus, this method is step-economical; additional advantages include retention of chirality, convenient handling and easy purification. A few hitherto unreported compounds were also prepared, and all final compounds were completely characterized by IR, mass, optical rotation, and 1H and 13C NMR studies.
- Santhosh,Durgamma,Shekharappa,Sureshbabu, Vommina V.
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p. 4874 - 4880
(2018/07/15)
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- Asymmetric solution-phase mixture aldol reaction using oligomeric ethylene glycol tagged chiral oxazolidinones
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Sorting tags are oligomeric structures that can be used as protecting groups or chiral auxiliaries enabling solution-phase mixture syntheses of multiple tagged compounds in one pot and allowing for facile and predictable chromatographic separation of products at the end of synthetic sequences. Perfluorinated hydrocarbon and oligomeric ethylene glycol (OEG) derivatives are known classes of sorting tags. Herein we describe the preparation of OEGylated chiral oxazolidinones and their use in asymmetric solution-phase mixture aldol reactions. Through the use of such oxazolidinones based on tyrosine four different individually tagged aldol adducts were obtained as a mixture, chromatographically demixed, detagged, and it was shown that these processes gave the desired aldol products in good yield and enantioselectivity.
- Turkyilmaz, Serhan,Wilcox, Craig S.
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p. 2031 - 2033
(2017/05/04)
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- Chiral ethylene-bridged flavinium salts: the stereoselectivity of flavin-10a-hydroperoxide formation and the effect of substitution on the photochemical properties
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A series of chiral non-racemic N1,N10-ethylene bridged flavinium salts 4 was prepared using enantiomerically pure 2-substituted 2-aminoethanols (R = isopropyl, phenyl, benzyl, 4-methoxybenzyl, 4-benzyloxybenzyl) derived from amino acids as the sole source of chirality. The flavinium salts were shown to form 10a-hydroperoxy- and 10a-methoxy-adducts with moderate to high diastereoselectivity depending on the ethylene bridge substituent originating from the starting amino acid. High diastereoselectivities (dr values from 80:20 to >95:5) were observed for flavinium salts bearing benzyl substituents attached to the ethylene bridge. The benzyl group preferred the face-to-face (syn) orientation relative to the flavinium unit; thereby effectively preventing nucleophilic attack from one side. This conformation was found to be the most stable according to the DFT calculations. Consequently, the presence of benzyl groups causes intermolecular fluorescence quenching resulting in a significant decrease in the fluorescence quantum yield from 11% for 4a bearing an isopropyl substituent to 0.3% for 4c containing a benzyl group and to a value lower than 0.1% for the benzyloxybenzyl derivative 4e.
- ?urek, Ji?í,Svobodová, Eva,?turala, Ji?í,Dvo?áková, Hana,Svoboda, Ji?í,Cibulka, Radek
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p. 1780 - 1791
(2017/11/17)
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- Rhodium-catalyzed borylation of aryl 2-pyridyl ethers through cleavage of the carbon-oxygen bond: Borylative removal of the directing group
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The rhodium-catalyzed reaction of aryl 2-pyridyl ethers with a diboron reagent results in the formation of arylboronic acid derivatives via activation of the C(aryl)-O bonds. The straightforward synthesis of 1,2-disubstituted arenes was enabled through catalytic ortho C-H bond functionalization directed by the 2-pyridyloxy group followed by substitution of this group with a boryl group. Several control experiments revealed that the presence of a sp2 nitrogen atom at the 2-position of the substrate and the use of a boron-based reagent were crucial for the activation of the relatively inert C(aryl)-O bond of aryl 2-pyridyl ethers.
- Kinuta, Hirotaka,Tobisu, Mamoru,Chatani, Naoto
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supporting information
p. 1593 - 1600
(2015/03/05)
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- Rigid spiroethers targeting the decoding center of the bacterial ribosome
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Continuing our efforts towards understanding the principles governing ribosomal recognition and function, we have synthesized and evaluated a series of diversely functionalized 5,6-, 6,6- and 7,6-spiroethers. These compounds successfully mimic natural aminoglycosides regarding their binding to the decoding center of the bacterial ribosome. Their potential to inhibit prokaryotic protein production in vitro along with their antibacterial potencies have also been examined.
- Mavridis, Ioannis,Kythreoti, Georgia,Koltsida, Konstantina,Vourloumis, Dionisios
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p. 1329 - 1341
(2014/03/21)
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- New practical synthesis of non-cross-linked polystyrene supported 2-phenylimino-2-oxazolidine
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A new practical method for the synthesis of a non-cross-linked polystyrene supported 2-phenylimino-2-oxazolidine chiral auxiliary is reported. This method started from the same material as in a previous synthesis, N-Boc-L-tyrosine ethyl ester, but the overall yield was 42.5%, which was higher than the copolymerisation method.
- Lu, Cuifen,Hu, Fuqiang,Chen, Zuxing,Yang, Guichun
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p. 276 - 277
(2012/09/22)
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- Synthesis of a new chiral auxiliary-Non-cross-linked polystyrene-supported oxazolidine-2-selone
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A new chiral auxiliary, non-cross-linked polystyrene-supported oxazolidine-2-selone was synthesized using N-Boc-l-tyrosine ethyl ester as starting material. The structure of the target product was detected by IR, NMR, elemental analysis, and the spectrum
- He, Xiping,Li, Jia,Lu, Cuifen,Chen, Zuxin,Yang, Guichun
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- α- and β-Substituted phosphonate analogs of LPA as autotaxin inhibitors
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Autotaxin (ATX) is an attractive pharmacological target due to its lysophospholipase D activity which leads to the production of lysophosphatidic acid (LPA). Blockage of ATX produced LPA by small molecules could be a potential anticancer chemotherapy. In our previous study, we have identified the two β-hydroxy phosphonate analogs of LPA (compounds f17 and f18) as ATX inhibitors. With this work, we investigated α- and β-substituted phosphonate analogs of LPA and evaluated them for ATX inhibitory activity. The stereochemistry of β-hydroxy phosphonates was also studied.
- Cui, Peng,McCalmont, William F.,Tomsig, Jose L.,Lynch, Kevin R.,Macdonald, Timothy L.
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p. 2212 - 2225
(2008/09/21)
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- Scope and mechanism of direct indole and pyrrole couplings adjacent to carbonyl compounds: Total synthesis of acremoauxin A and oxazinin 3
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Full details are provided for a recently invented method to couple indoles and pyrroles to carbonyl compounds. The reaction is ideally suited for structurally complex substrates and exhibits high levels of chemoselectivity (functional group tolerability), regioselectivity (coupling occurs exclusively at C-3 of indole or C-2 of pyrrole), stereoselectivity (substrate control), and practicality (amenable to scaleup). In addition, quaternary stereocenters are easily and predictably generated. The reaction has been applied to a number of synthetic problems including total syntheses of members of the hapalindole family of natural products, ketorolac, acremoauxin A, and oxazinin 3. Mechanistically, this coupling protocol appears to operate by a single electron-transfer process requiring generation of an electron-deficient radical adjacent to a carbonyl which is then intercepted by an indole or pyrrole anion.
- Richter, Jeremy M.,Whitefield, Brandon W.,Maimone, Thomas J.,Lin, David W.,Castroviejo, M. Pilar,Baran, Phil S.
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p. 12857 - 12869
(2008/09/16)
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- Arylaminoethyl amides as noncovalent inhibitors of cathepsin S. Part 2: Optimization of P1 and N-aryl
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A systematic study of anilines led to the discovery of a metabolically robust fluoroindoline replacement for the alkoxy aniline toxicophore in 1. Investigations of the P1 pocket resulted in the discovery of a wide tolerance of functionality leading to the discovery of 11 as a potent and selective inhibitor of cathepsin S.
- Alper, Phillip B.,Liu, Hong,Chatterjee, Arnab K.,Nguyen, Khanhlinh T.,Tully, David C.,Tumanut, Christine,Li, Jun,Harris, Jennifer L.,Tuntland, Tove,Chang, Jonathan,Gordon, Perry,Hollenbeck, Thomas,Karanewsky, Donald S.
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p. 1486 - 1490
(2007/10/03)
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- Ligand creation via linking - A rapid and convenient method for construction of novel supported PyOX-ligands
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A novel supported amino alcohol linker was synthesized and utilized for attachment of picolinic acid derivatives onto different supports. When the resin bound molecule was further activated, the PyOX-moiety could be constructed reliably in enantiopure form. Furthermore, an efficient Pd-catalyzed modification of a picolinic acid derivative is presented.
- Oila, Markku J.,Tois, Jan E.,Koskinen, Ari M.P.
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p. 10748 - 10756
(2007/10/03)
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- Syntheses of amino alcohols and chiral C2-symmetric bisoxazolines derived from O-alkylated R-4-hydroxyphenylglycine and S-tyrosine
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Chiral C2-symmetric bisoxazolines 1b-f and 2b,c, derived from 4′-O-alkylated R-4-hydroxyphenylglycine or S-tyrosine, were prepared. As intermediates, a series of chiral amino alcohols possessing substituted phenolic groups was prepared and fully characterized.
- Caplar, Vesna,Raza, Zlata,Katalenic, Darinka,Zinic, Mladen
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- A practical synthesis of enantiopure (S)-4-(4-hydroxybenzyl)-oxazolidin-2-one
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A high yielding four-step synthesis of enantiopure 4-(4-hydroxybenzyl)-oxazolidin-2-one (S)-1 from N-Boc-L-tyrosine is described. (S)-1 is a key intermediate for the preparation of a number of polymer supported Evans' oxazolidin-2-ones that have been employed previously for solid supported asymmetric synthesis.
- Green, Rachel,Taylor, Piers J. M.,Bull, Steven D.,James, Tony D.,Mahon, Mary F.,Merritt, Andy T.
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p. 2619 - 2623
(2007/10/03)
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- 5-amino-4-hydroxyhexanoic acid derivatives
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Compounds of formula I STR1 or their hydroxy-protected derivatives, and compounds of formula I' STR2 wherein T is an acyl radical of formula Z STR3 wherein Rz is unsubstituted or substituted hydrocarbyl wherein at least one carbon atom has been replaced by a hetero atom with the proviso that a hetero atom is not bonded directly to the carbonyl to which the radical Rz is bonded, alkyl having two or more carbon atoms, lower alkenyl, lower alkynyl, aryl or unsubstituted or substituted amino, and wherein the radicals R1, B1, R2, R3, A1, A2 and NR4 R5 are as defined in the description, and precursors thereof, are described. The compounds have pharmaceutical activity, for example in the treatment of retroviral diseases, such as AIDS.
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- Resin type can have important effects on solid phase asymmetric alkylation reactions
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A new N-propionylated oxazolidinone 1 is prepared; asymmetric alkylations of this auxiliary proceed with varying yields and enantioselectivities when supported on Merrifield, Wang and TentaGel R PHB resins.
- Burgess, Kevin,Lim, Dongyeol
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p. 785 - 786
(2007/10/03)
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- TIGHT-BINDING INHIBITORS OF LEUKOTRIENE A4 HYDROLASE
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Inhibitors of leukotriene A 4 hydrolase are disclosed, corresponding to Formula I, below: STR1 wherein the depicted--NH 2 group is in the (S) configuration;--W is--CH 2 SH,--CH 2 NH. sub.2 or C(=Z)--Y, wherein =Z is =O, or--H and--OH; and--Y is selected from the group consisting of (a) phenyl, (b) trifluoromethylphenyl, (c) carboxyphenyl, (d) benzyl, (e) C 1-C 6 alkylenecarboxyl, (f) C. sub.1-C 6 alkyl, (g) C 2-C 6 alkenyl, (h) C 1-C 6 alkylenephenyl and (i)--C(=O)--X--R. sup.1 wherein X is O or NH and, R 1 is selected from the group consisting of C 1-C 6 alkyl, C 1-C 6 alkylenecarboxyl, and benzyl; R 2 is hydrogen, benzyloxy or 2-naphthylmethyloxy, and a pharmaceutically acceptable acid addition salt thereof. Inhibitors wherein--W is--CH 2 SH,--CH 2 NH 2 or C(=Z)--Y wherein =Z is =O and--Y is--C(=O)--X--R. sup.1 are particularly preferred, as are those compounds wherein =Z is = O and--Y is selected from the group consisting of (a) phenyl, (b) trifluoromethylphenyl, (c) carboxyphenyl, (d) benzyl, (e) C 1-C 6 alkylenecarboxyl, (f) C 1-C 6 alkyl, (g) C 2-C 6 alkenyl, (h) C 1-C 6 alkylenephenyl. An inhibitor where--W is--CH 2 SH,--CH 2 NH 2 or C(=Z)--Y wherein =Z is =O and--Y is--C(=O)--X--R 1 is particularly preferred, as are those inhibitor compounds where =Z is =O and--Y is (a)--(h) .
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- Synthesis of Chiral N-Protected β-Amino Alcohols by the Use of UNCAs
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A facile synthesis of a wide variety of N-protected β-amino alcohol derivatives under mild conditions is described.N-urethane protected amino acid N-carboxyanhydrides (UNCAs) were used as starting material and reduced into the corresponding alcohols with
- Fehrentz, Jean-Alain,Califano, Jean-Christophe,Amblard, Muriel,Loffet, Albert,Martinez, Jean
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p. 569 - 572
(2007/10/02)
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- The Influence of Protecting Group Character on the Diastereoselectivity of Thiazolidine Ring Formation from Amino Aldehydes and Cysteine
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A series of 2-(1'-aminoalkyl)-thiazolidine-4-carboxylic acid derivatives was synthesized by condensation of (R)- or (S)-Cys with the amino aldehydes obtained from N-Boc-protected (S)-Ile, (S)-Leu, O-Bzl-(S)-Tyr, (S)- and (R)-Phe, and N-Z-(S)-Phe, N-Pht-(S)-Phe and N-(Pht)-(R)-Phe. All compounds were studied by 1H NMR and CD. The 2D NOESY experiments were carried out to determine the configuration of the newly formed stereogenic centre in position 2 of the thiazolidine ring. It was found that the configuration on the thiazolidine C2 atom is R or S when N-Boc- and N-Z-(S)-amino aldehydes or N-Boc- and N-Z-(R)-amino aldehydes are used in the reaction, respectively. The situation is opposite in the case of N-Pht-Phe derived amino aldehydes. The relation between the C2 atom configuration and the shape of CD spectra is discussed. Key words: 2-(1'-aminoalkyl)-thiazolidine-4-carboxylic acids, amino aldehydes, cysteine, stereoselectivity, absolute configuration, NMR, CD.
- Wyslouch, Aleksandra,Lisowski, Marek,Siemion, Ignacy Z.
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p. 117 - 130
(2007/10/02)
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- A facile synthesis of chiral N-protected β-amino alcohols
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Chiral N-protected β-amino alcohols are easily obtained by NaBH4 reduction of mixed anhydrides of N-protected α-amino acids in an organic/aqueous medium. The alcohols obtained from side chain or main chain reduction of N-protected aspartic acid are converted in good yields into lactones.
- Rodriguez,Llinares,Doulut,Heitz,Martinez
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p. 923 - 926
(2007/10/02)
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- A synthesis of (-)-bursatellin
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A synthesis of (-)-bursatellin has been accomplished by an application of a new procedure for oxidation at a benzylic position with K2S2O8 to 1-acetoxy-2(S)-N-Boc-amino-3-(4-benzyloxyphenyl) propane as a key step.
- Kawamine,Takeuchi,Miyashita,Irie,Shimamoto,Ohfune
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p. 3170 - 3171
(2007/10/02)
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- New Approaches to the Synthesis of trans-Alkene Isosteres of Dipeptides
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Two new syntheses of protected dipeptide analogues bearing a trans carbon-carbon double bond in place of the amide linkage are reported.One route is a linear synthesis employing the rearrangement of an allylic selenide to a protected allylic amine.The second route is convergent and uses the Julia olefin synthesis in a key step.The latter route is fully stereocontrolled and has been used to prepare protected trans-alkene isosteres of the dipeptides TyrAla, PhePhe, LeuPhe, and LeuLeu.
- Spaltenstein, Andreas,Carpino, Philip A.,Miyake, Fumio,Hopkins, Paul B.
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p. 3759 - 3766
(2007/10/02)
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- A STEREOCONTROLLED SYNTHESIS OF TRANS-ALKENE ISOSTERES OF DIPEPTIDES
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A general synthetic route to trans-alkene isosteres of protected dipeptides is reported.This sequence permits the fully stereocontrolled preparation of these isosteres in optically active form and in quantities sufficient for further biological study.Prep
- Spaltenstein, Andreas,Carpino, Philip A.,Miyake, Fumio,Hopkins, Paul B.
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p. 2095 - 2098
(2007/10/02)
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