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The Synthesis and Configurational Stability of Differentially Protected beta-Hydroxy-beta-amino Aldehydes

Syntheses of 1,1-dimethylethyl (S)-4-formyl-2,2-dimethyl-3-oxazolidinecarboxylate (5) and 1,1-dimethylethyl (4S-trans)-4-formyl-2,2,5-trimethyl-3-oxazolidinecarboxylate (6) from commercially available serine and threonine derivatives are described.The method involves selective reduction of the corresponding oxazolidine esters 3 and 4 using diisobutylaluminum hydride at low temperature.These differentially protected beta-hydroxy-alpha-amino aldehydes are also shown to be produced in 93-95 percent enantiomeric excess (via NMR and HPLC analysis of the Mosher esterderivatives 8 and epi-8)-thus making them useful as chiral, nonracemic synthons for asymmetric synthesis.

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Chiral non-racemic bicyclic lactams. Auxiliary-based asymmetric reactions

The chiral non-racemic bicyclic lactam has proven to be an exceptionally versatile chiral template for the asymmetric construction of a variety of optically pure compounds. Those lactams derived from keto acids have been applied to the synthesis of a host of natural products and pharmacologically interesting heterocycles and carbocycles. A variety of mechanistic questions regarding facial stereo-control have been investigated using the chiral template as the key probe. However, further elucidation of the subtle mechanistic principles involved await further study.

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ORALLY AVAILABLE SPHINGOSINE 1-PHOSPHATE RECEPTOR AGONISTS AND ANTAGONISTS

The present invention relates to S1P analogs that have activity as S1Preceptor modulating agents and the use of such compounds to treat diseases associated with inappropriate S1P receptor activity. The compounds have the general structure (I) wherein R11 is C5-C18 alkyl or C5-C18 alkenyl; Q is selected from the group consisting of C3-C6 optionally substituted cycloalkyl, C3-C6 optionally substituted heterocyclic, C3-C6 optionally substituted aryl C3-C6 optionally substituted heteroaryl and; R2 is selected from the group consisting of H, C1-C4 alkyl, (C1-C4 alkyl)OH and (C1-C4 alkyl)NH2; R23is H or C1-C4 alkyl, and R15 is a phosphonate ester or a phosphate ester or a pharmaceutically acceptable salt or tautomer thereof.

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Steric and electronic requirements of amide and ester groups in benzylidenemalonates

Stereoisomeric benzylidinemalonates have been synthesised. In the case of N-(2-ethoxycarbonyl-3-phenylpropenoyl)-2-oxazolidinone, both E- and Z-isomers could be obtained, but the Z-isomer isomerised (> 95%) to the E-isomer in the presence of catalytic amounts of Rh(I) complex catalysts. For ethyl tert-butylamidobenzalmalonate, the Z-isomer initially predominates under Knoevenagel conditions, but is very readily converted into the more stable E-isomer, which is here isolated stereoisomerically pure and is the only product of other synthetic routes. The configuration of benzylidinemalonates was established in two cases by X-ray crystallography, and the relative stability of the isomeric forms correctly simulated by MM2 calculations. In both the amide and oxazolidinone series, asymmetric hydrogenation catalysed by cationic Rh complexes gave a configurationally stable product cleanly but in low e.e..

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Synthesis of D-erythro-sphingosine and D-erythro sphinganine via 3- ketosphinganine

D-erythro- sphingosine and D-erythro-sphinganine can be produced in protected form from serine by a synthetic approach in which the normal biological intermediate 3-ketosphinganine in protectyed form, is a key synthetic intermediate. The sequence is short and convergent, proceeds in good overall yields (? 30% for 6 steps) and with excellent stereocontrol (>91% de, >95% ee).

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Urethane-protected amino acid-N-carboxyanhydrides

Urethane-protected NCAs and MTAs are prepared by reacting an NCA or NTA with a haloformate in an inert diluent, under anhydrous conditions and in the presence of a tertiary nitrogen-containing base having an atom or functional group sufficiently electron rich and positioned relative to the nitrogen of said base so as to render said atom or group capable of complexing with the H–N< group of said N-carboxyanhydride or N-thiocarboxyanhydride but able to generate N-carboxyanhydride or N-thiocarboxyanhydride anionic complexes capable of reacting with the haloformate. We¡¯ll also look at important developments in the pharmaceutical industry because understanding organic chemistry is important in understanding health, medicine, the role of 3190-70-3, and how the biochemistry of the body works.Formula: C7H11NO3

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Oxazolidine – Wikipedia,
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Solution and solid state studies of hydrogen bonding in substituted oxazolidinones by spectroscopic and quantum chemical methods

Structure and hydrogen bonding interactions of bioactive oxazolidinones have been studied by means of NMR and vibrational spectroscopies and quantum chemical calculations. We have demonstrated that oxazolidinone derivatives form hydrogen bonds in solution and solid state. Conformational space search has revealed predominant conformations in solution. In low polarity solvents, such as chloroform, dimers are formed presumably by intermolecular hydrogen bonds between two oxazolidinone molecules forming the most stable complexes, which has also been found in the solid state by IR spectroscopy and crystallography. In solvents of higher polarities, like methanol and dimethylsulfoxide, intermolecular interactions with solvent molecules and in dimers are present. As expected, raising the temperature broke hydrogen bonds, which was reflected in down-field chemical shifts of corresponding resonances. On the other hand, raising the solution concentration considerably affected oxazolidinone resonances only in chloroform, corroborating the formation of oxazolidinone dimers. These results may help in better understanding oxazolidinone structure, properties and interactions when designing new bioactive compounds and pharmaceutical products.

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Conversion of Ester Moieties to 4-Bromophenyl Groups via Electrocyclic Reaction of Dibromocyclopropanes

(Chemical Equation Presented) Conversion of ester moieties into 4-bromophenyl groups was effected by means of a four-step protocol: a Grignard reaction of the ester with allylmagnesium halides, a ring-closing metathesis, dibromocyclopropanation, and an electrocyclic reaction of the dibromocyclopropanes.

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Short communication: Silica sulfuric acid: A versatile and reusable heterogeneous catalyst for the synthesis of N-ACYL carbamates and oxazolidinones under solvent-free conditions

Silica sulfuric acid catalyzes efficiently the reaction of carbamates and oxazolidinones with anhydrides under solvent-free conditions. All the reactions were done at room temperature and the N-acyl carbamates and oxazolidinones were obtained with high yields and purity via an easy work-up procedure. This method is attractive and is in a close agreement with green chemistry.

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A METHOD FOR THE PREPARATION OF ZOLMITRIPTAN

In the preparation of zolmitriptan of formula III the reduction of the diazonium salt to (5)-4-(4- hydrazinobenzyl)-l,3-oxazolidin-2-one of formula IV is performed in a more concentrated mixture and by the effect on an alkali metal disulphite, preferably sodium disulphite. A zolmitriptan toluene solvate, characterized by a toluene content of 9 to 14 % by weight according to the gas chromatography determination and by a maximum of the corresponding mass loss at temperatures of about 111C in the gravimetric analysis record. A zolmitriptan toluene solvate, showing strong Raman bands at the wave numbers of 1443 and 1354 cm-1, characteristic for the crystal lattice of zolmitriptan with built-in toluene, and further marked bands at 1004 and 786 cm-1, characteristic for toluene.

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