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A one-pot, convenient and practical method for N-acylation of 2- oxazolidinone chiral auxiliaries directly with acids in the presence of pivaloyl chloride and triethylamine is described.

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Reference:
Oxazolidine – Wikipedia,
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Acetylhypobromite and tert-butylhypochlorite are the reagents of choice to synthesize new chiral N-bromo and N-chloro carbamates, amides, imides and oxazolidinones.

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The thermal reaction of 3-[(1S)-2-alkoxy-1-apocamphanecarbonyl]-2-oxazolones with dialkyl azodicarboxylates results in exclusive formation of [4 + 2] type cycloadducts with moderate levels of diastereofacial selection, which serve as versatile chiral synthons for a wide variety of 4-alkyl and 4-alkyl-2-oxazolidinones as well as alpha-amino acids.

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The invention further relates to the use of the compound or a 2,3 – pharmaceutically acceptable (IDO) salt of the compound or a, pharmaceutically acceptable salt of the compound or a pharmaceutically. acceptable salt, thereof in the preparation of a (I) pharmaceutical composition containing the compound or a pharmaceutically acceptable, salt of the compound or a pharmaceutically acceptable salt of the compound, or a pharmaceutically acceptable salt thereof/IDO, IDO, (I). (by machine translation)

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In response to a recent literature report by Decicco and Leathers, the work of Hale, Delisser, and Manaviazar (1992) on the asymmetric synthesis of (3R)- and (3S)-piperazic acids has been reinvestigated, and the originally claimed product yields fully substantiated. The claims made in reference 13 about the proportions of cyclised product 6 and starting bromide 20 isolated from the low temperature electrophilic hydrazination-nucleophilic cyclisation of 20 with di-t-butylazodicarboxylate (DBAD) and DMPU as an additive are inaccurate. The retro-hydrazination reaction that they claim is problematic when DMPU is added to the hydrazinated reaction mixture has been demonstrated not to have a seriously detrimental effect on cyclisation product yield and to be unimportant. The other main ion of reference 13, that the electrophilic hydrazination and nucleophilic cyclisation of 20 gives 6 in 91% isolated yield when n-Bu4NI is employed as an additive (instead of DMPU) has also been shown to be in error. We have carefully repeated a scaled-down version of the n-Bu4NI catalysed procedure and have found that 6 is generally isolated in yields of 50-56% after flash chromatography. We have concluded that n-Bu4NI does not significantly increase the yields of cyclisation products 6 or 17 when it is employed as a cyclisation additive. Herein, we report details of our two preferred ‘crude’ experimental procedures for preparing the enantiomers of piperazic acid in high optical purity, neither of which requires chromatographic purification of the reaction intermediates en route. Both these preferred ‘crude’ methods for preparing 11 and 19 have been consistently reproduced many times in these laboratories over the past few years. In our view, they remain the most expedient and highest yielding methods currently available for obtaining 11 and 19 in high optical purity.

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Methanethiosulfonate reagents may be used to introduce virtually unlimited structural modifications in enzymes via reaction with the thiol group of cysteine. The covalent coupling of enantiomerically pure (R) and (S) chiral auxiliary methanethiosulfonate ligands to cysteine mutants of subtilisin Bacillus lentus induces spectacular changes in catalytic activity between diastereomeric enzymes. Amidase and esterase kinetic assays using a low substrate approximation were used to establish k(cat)/K(M) values for the chemically modified mutants, and up to 3-fold differences in activity were found between diastereomeric enzymes. Changing the length of the carbon chain linking the phenyl or benzyl oxazolidinone ligand to the mutant N62C by a methylene unit reverses which diastereomeric enzyme is more active. Similarly, changing from a phenyl to benzyl oxazolidinone ligand at S166C reverses which diastereomeric enzyme is more active. Chiral modifications at S166C and L217C give CMMs having both high esterase k(cat)/K(M)’s and high esterase to amidase ratios with large differences between diastereomeric enzymes. Copyright (C) 2000 Elsevier Science Ltd.

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Disclosed are compounds having the formula (I): wherein R1, R2 and R3 are as defined herein, and methods of making and using the same, including use as inhibitors of BMP1, TLL1 and/or TLL2 and in treatment of diseases associated with BMP1, TLL1 and/or TLL2 activity.

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An enantioselective route for oxazoline 4, a key fragment toward the asymmetric synthesis of leiodelide A, is described. We synthesized northern subunit 6 through a Julia-Lythgoe olefination and subsequent Sharpless asymmetric dihydroxylation. Moreover, a highly diastereoselective method using well-established Evans’ asymmetric aldol condensation was developed for preparation of southern fragment 5. The additional feature of this synthetic route is the formation of oxazoline 4 through DAST-promoted cyclization of the amidation product from subunits 5 and 6.

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(Matrix Presented) A general amination strategy for the N-alkynylation of carbamates, sulfonamides, and chiral oxazolidinones and imidazolidinones is described. A variety of substituted ynamides are available by deprotonation of amides with KHMDS followed by reaction with CuI and an alkynyl bromide.

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O-Methyloscillatoxin D and its analogues were concisely synthesized by a bioinspired intramolecular Mukaiyama aldol reaction as a key step, which involves the construction of a novel spiro-ether moiety.

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