- Elucidating the Origin of diastereoselectivity in a self-replicating system: Selfishness versus altruism
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We have investigated a diastereoselective self-replicating system based on a cycloaddition of a fulvene derivative and a maleimide using a two-pronged approach of combining NMR spectroscopy with computational modelling. Two diastereomers are formed with identical rates in the absence of replication. When replication is enabled, one diastereomer takes over the resources as a "selfish" autocatalyst, while exploiting the competitor as a weak "altruist", resulting in a diastereoselectivity of 16:1. We applied 1D and 2D NMR spectroscopic techniques supported by ab initio chemical shifts as well as ab initio molecular dynamics simulations to study the structure and dynamics of the underlying network. This powerful combination allowed us to decipher the energetic and structural rationale behind the observed behaviour, while static computational methods currently used in the field did not.
- Dieckmann, Arne,Beniken, Sabrina,Lorenz, Christian D.,Doltsinis, Nikos L.,Von Kiedrowski, Guenter
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- Trifluoromethyl-substituted analogues of 1-aminocyclobutane-1-carboxylic acid
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Trifluoromethyl-substituted analogues of the 1-amino-cyclobutane-1- carboxylic acid - 1-amino-3-(trifluoromethyl) cyclobutanecarboxylic and 1-amino-3,3-bis(trifluoromethyl)cyclobutane-carboxylic acids - have been synthesized from 1,3-dibromoacetone dimethyl ketal. The key step of the syntheses is a transformation of the acid moiety into the trifluoromethyl group using SF4 and HF. Georg Thieme Verlag Stuttgart.
- Radchenko, Dmytro S.,Mykhailiuk, Pavel K.,Bezdudny, Andrii V.,Komarova, Igor V.
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- Preparation method 3 - oxocyclobutane-based carboxylic acid
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The invention discloses a preparation method of 3 -oxocyclobutane-based carboxylic acid, and belongs to the technical field of synthesis of medical intermediates. The ketone is protected from 1, 3 -dihydroxyacetone by condensation with trimethyl orthoformate to give 2, 2 -dimethoxy -1, 3 -propanediol, followed by reaction with malonate to give 3, 3 -dimethylcyclobutyl -1, 1 -dicarboxylic acid diester, followed by hydrolysis under acidic conditions. Decarboxylation and deprotection to yield 3 -oxocyclobutane-based carboxylic acids. The method has the advantages of high yield, common and easily available raw materials, simple flow and industrial amplification prospect.
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Paragraph 0027-0029
(2021/10/27)
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- Preparation method of intermediate for synthesizing 3 -oxo -1 -cyclobutane carboxylic acid
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The invention discloses a preparation method for synthesizing 3 -oxo -1 -cyclobutane carboxylic acid intermediate 1, 1 - bis (prop -2 -) 3, 3 -dimethoxycyclobutane -1 and 1 - dicarboxylic acid ester (compound I): using potassium isopropoxide as a base, 1 1 -1 as a solvent, and plays an important role in the yield and purity method of 3 the 3 - final product, DMAc which is prepared 1 - or -2 - I
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Paragraph 0031-0032; 0035-0037; 0040-0043
(2021/09/29)
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- Preparation method of 3-(benzyloxy)-1-cyclobutanone
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The invention relates to the technical field of organic synthesis, and specifically relates to synthesis of a medical intermediate 3-(benzyloxy)-1-cyclobutanone, according to the invention, 3-dibromo-2,3-dibromo-2,3,3-tetramethylpiperidine and diisopropyl malonate are used as initial raw materials; firstly, cyclobutane (I) is obtained through a nucleophilic substitution reaction; deprotection andhydrolysis are carried out on a compound (I) under the action of an acid to obtain 3-oxocyclobutanecarboxylic acid (II), the compound (II) is converted into a carboxylic acid silver salt, a Hunsdiecker reaction is carried out on the carboxylic acid silver salt and elemental bromine to obtain alkyl bromide (III), and a nucleophilic substitution reaction is performed on the compound (III) and benzylalcohol to obtain 3-(benzyloxy)-1-cyclobutanone (IV). The method provides a simple industrial production route for 3-(benzyloxy)-1-cyclobutanone, and has the advantages of simple reaction operation,mild reaction conditions and low cost.
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Paragraph 0043-0045
(2020/07/12)
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- Intramolecular functional group differentiation as a strategy for the synthesis of bridged bicyclic β-amino acids
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Differentiation of identical electrophilic functional groups (carboxylates) by a strategically placed internal nucleophile (an amino group) in cyclic precursors was used as a key general approach to functionalized azabicyclic scaffolds. The utility of the method was demonstrated by the synthesis of three bicyclic β-amino acids (analogues of nipecotic acid), which were prepared in good yields and on a relatively large scale.
- Tymtsunik, Andriy V.,Kokhan, Serhii O.,Ivon, Yevhen M.,Komarov, Igor V.,Grygorenko, Oleksandr O.
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p. 22737 - 22748
(2016/03/26)
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- SPIROCYCLIC HAT INHIBITORS AND METHODS FOR THEIR USE
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Compounds having a structure of Formula (IX) or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof, wherein R1, R2a, R2b, R3a, R3b, R4a, R4b, Q1----Q2, R6, R7, A, B, W, x, and y are as defined herein and are provided. Pharmaceutical compositions comprising such compounds and methods for treating various HAT-related conditions or diseases, including cancer, by administration of such compounds are also provided.
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Page/Page column 752
(2016/04/10)
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- Gram-scale synthesis of 3,5-methanonipecotic acid, a nonchiral bicyclic β-amino acid
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A scalable synthesis was developed of 3,5-methanoni?pecotic acid (3-azabicyclo[3.1.1]heptane-1-carboxylic acid), a rare example of a conformationally constrained nonchiral β-amino acid, potentially useful in peptide engineering and peptidomimetic drug design. A retrosynthetic strategy based on disconnections exclusively within the symmetry planes of the target and the intermediate molecules was found to be useful and might deliver expedite syntheses in other similar cases. Georg Thieme Verlag Stuttgart New York.
- Tymtsunik, Andriy V.,Bilenko, Vitaliy A.,Grygorenko, Oleksandr O.,Komarov, Igor V.
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p. 355 - 358
(2014/03/21)
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- ANTIBACTERIAL AGENTS
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Antibacterial compounds of formula (I) are provided, as well as stereoisomers and pharmaceutically acceptable salts and esters thereof; pharmaceutical compositions comprising such compounds; methods of treating bacterial infections by the administration of such compounds; and processes for the preparation of such compounds.
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Page/Page column 104; 105
(2014/10/18)
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- Synthesis of 2-azaspiro[3.3]heptane-derived amino acids: Ornitine and GABA analogues
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Synthesis of 6-amino-2-azaspiro[3.3]heptane-6-carboxylic acid and 2-azaspiro[3.3]heptane-6-carboxylic acid was performed. Both four-membered rings in the spirocyclic scaffold were constructed by subsequent ring closure of corresponding 1,3-bis-electrophil
- Radchenko, Dmytro S.,Grygorenko, Oleksandr O.,Komarov, Igor V.
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scheme or table
p. 515 - 521
(2010/11/04)
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- AZETIDINE AND CYCLOBUTANE DERIVATIVES AS JAK INHIBITORS
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The present invention relates to azetidine and cyclobutane derivatives, as well as their compositions, methods of use, and processes for preparation, which are JAK inhibitors useful in the treatment of JAK-associated diseases including, for example, inflammatory and autoimmune disorders, as well as cancer.
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Page/Page column 46
(2009/09/28)
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- AZETIDINES AND CYCLOBUTANES AS HISTAMINE H3 RECEPTOR ANTAGONISTS
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The invention relates to compounds of formula (I) wherein R, R0, R1, m, n and X1 to X4 have the meaning as cited in the description and the claims. Said compounds are useful as Histamine H3 receptor antagonists. The invention also relates to pharmaceutical compositions, the preparation of such compounds as well as the production and use as medicament.
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Page/Page column 131-132
(2010/01/29)
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- AMINO ACID COMPOUNDS
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[Problem] To provide novel compounds that are S1P1 receptor agonists and exhibit an immunosuppressive activities by inducing lymphocyte sequestration in secondary lymphoid tissues. In addition, to provide a pharmaceutical agent which comprises the compounds as an effective component, in particular to provide a therapeutic and/or prophylactic agent for an autoimmune disease and the like. [Solving Means] Amino acid compounds that are represented by the following Formula (1) are provided
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Page/Page column 44
(2009/12/23)
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- Synthesis of conformationally restricted glutamic acid analogs based on the spiro[3.3]heptane scaffold
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A library of isomeric glutamic acid analogs based on the spiro[3.3]heptane skeleton is designed. Two members of the library, (R)- and (S)-2-amino-spiro[3.3]heptane-2,6-dicarboxylic acid hydrochlorides, were synthesized. The stereochemistry of the synthesi
- Radchenko, Dmytro S.,Grygorenko, Oleksandr O.,Komarov, Igor V.
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scheme or table
p. 2924 - 2930
(2009/07/04)
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- 1-(1-CYCLOBUTYL-4-PIPERIDINYL)-1,3-DIHYDRO-2H-BENZIMIDAZOL-2-ONE DERIVATIVES WHICH HAVE ACTIVITY ON THE ML RECEPTOR AND THEIR USE IN MEDICINE
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Compounds of formula I or a salt thereof are provided wherein R4, R5, R6, Q, L and R are as defined in the description. Uses of the compounds as medicaments and in the manufacture of medicaments for treating psychotic disorders and cognitive impairments are disclosed. The invention further discloses pharmaceutical compositions comprising the compounds.
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Page/Page column 45-46
(2008/12/04)
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- 6,6-BICYCLIC RING SUBSTITUTED HETEROBICYCLIC PROTEIN KINASE INHIBITORS
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Compounds of the formula (I) and pharmaceutically acceptable salts thereof, wherein XI, X2, X3, X4, X5, X6, X7, R1, and Q1 are defined herein, inhibit the IGF-1R enzyme and are useful for the treatment and/or prevention of hyperproliferative diseases such as cancer, inflammation, psoriasis, allergy/asthma, disease and conditions of the immune system, disease and conditions of the central nervous system.
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Page/Page column 339
(2008/06/13)
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- AMINO CYCLOBUTYLAMIDE MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY
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The present invention is directed to compounds of the formulas I and II : wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R15, R16, R17, R18, R19, R25, R26, Y, Z, l, m, n and the broken lines are as defined herein which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptor CCR-2.
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