Showing papers on "Oxazolidine published in 2007"

Isolation and structure elucidation of thiazomycin- a potent thiazolyl peptide antibiotic from Amycolatopsis fastidiosa.

Abstract: Thiazolyl peptides are a class of rigid macrocyclic compounds richly populated with thiazole rings. They are highly potent antibiotics but none have been advanced to clinic due to poor aqueous solubility. Recent progress in this field prompted a reinvestigation leading to the isolation of a new thiazolyl peptide, thiazomycin, a congener of nocathiacins. Thiazomycin possesses an oxazolidine ring as part of the amino-sugar moiety in contrast to the dimethyl amino group present in nocathiacin I. The presence of the oxazolidine ring provides additional opportunities for chemical modifications that are not possible with other nocathiacins. Thiazomycin is extremely potent against Gram-positive bacteria both in vitro and in vivo. The titer of thiazomycin in the fermentation broth was very low compared to the nocathiacins I and III. The lower titer together with its sandwiched order of elution presented significant challenges in large scale purification of thiazomycin. This problem was resolved by the development of an innovative preferential protonation based one- and/or two-step chromatographic method, which was used for pilot plant scale purifications of thiazomycin. The isolation and structure elucidation of thiazomycin is herein described.

Efficient Oxidative Conversion of Aldehydes to 2-Substituted Oxazolines and Oxazines Using (Diacetoxyiodo)benzene

Abstract: An efficient synthesis of 2-substituted oxazolines from aldehydes and 2-amino alcohol using (diacetoxyiodo)benzene as an oxidant, is reported. (Diacetoxyiodo)benzene acts as a mild dehydrogenating agent to convert the initially formed oxazolidine from aldehyde and 2-amino alcohol to furnish 2-substituted oxazoline. Similarly, 3-aminopropanol and aldehydes gives the corresponding 2-substituted oxazines.

Synthesis of oxazolidines using DMSO/P4O10 as a formaldehyde equivalent

Abstract: Compounds containing a substituted oxazolidine ring were prepared in excellent yields in two steps from cis or trans 3-phenylglycidate. When an electron donating amine was used in the nucleophilic opening of an epoxide, treatment of the resulting β-amino-α-hydroxy ester with DMSO/P 4 O 10 led to the formation of cis or trans oxazolidines. This simple and practical procedure was readily adapted to the synthesis of enantiopure oxazolidines, using DMSO/P 4 O 10 because of the availability of the enantiopure halohydrins from enzymatic reduction of the β-chloro-α-ketoester.

Intramolecular chiral relay at stereogenic nitrogen: oxazolidine catalysts derived from Ephedra alkaloids

Abstract: A series of oxazolidines have been prepared by reaction of either (1 R ,2 S )-ephedrine or (1 S ,2 S )-pseudoephedrine with salicylaldehyde derivatives. The resultant oxazolidines were used as catalytic ligands in the addition of diethylzinc to a variety of aromatic and aliphatic aldehydes. It was determined that the (1 R ,2 S )-ephedrine based oxazolidine derivative 9 gave the highest enantioselectivities.

Conformational preferences of pseudoproline residues.

Abstract: The conformational study on N-acetyl-N‘-methylamides of oxazolidine and thiazolidine residues (Ac-Oxa-NHMe and Ac-Thz-NHMe) is carried out using ab initio HF and density functional B3LYP methods wi...

Chemistry of polyhalogenated nitrobutadienes, 4: reactions of mono-, bis-, and tris(4-tolylthio) derivatives of 2 nitroperchloro-1,3-butadiene with α,β-bifunctional nucleophiles

Abstract: The reaction of 1-(4-tolylthio)-, 1,1-bis(4-tolylthio)-, or 1,1,3-tris(4-tolylthio)perchloro-2-nitro- 1,3-butadiene with α,β-bifunctionalized ethanes such as N,N-, N,O,-, N,S-, O,S-, S,S-, or O,O- bisnucleophiles leads to both, highly functionalized 2-(1-nitroallylidene) derivatives of imidazolidine, oxazolidine, thiazolidine, (1,3)oxathiolane, or (1,3)dithiolane, respectively, and to the open chain, next higher thiolated buta-1,3-diene. The product distribution is highly sensitive to modifications of the reaction conditions: apart from changes of molar ratios of substrates and reagents the reaction temperature plays an important role. Thus, increase of the reaction temperature favours formation of the 1,3-heterocyclic ring. In all cases, extensive spectroscopic investigations have been performed and, in the case of the (1,3)oxathiolane also an X-ray analysis.

Anthracycline-formaldehyde conjugates and their targeted prodrugs.

Abstract: The sequence of research leading to a proposal for anthracycline cross-linking of DNA is presented.The clinical anthracycline antitumor drugs are anthraquinones, and as such are redox active. Their redoxchemistry leads to induction of oxidative stress and drug metabolites. An intermediate in reductive glycosidiccleavage is a quinone methide, once proposed as an alkylating agent of DNA. Subsequent research nowimplicates formaldehyde as a mediator of anthracycline-DNA cross-linking. The cross-link at 5′-GC-3′sites consists of a covalent linkage from the amino group of the anthracycline to the 2-amino groupof the G-base through a methylene from formaldehyde, hydrogen bonding from the 9-OH to the G-base onthe opposing strand, and hydrophobic interactions through intercalation of the anthraquinone. The combinationof these interactions has been described as a virtual cross-linkof DNA. The origin of the formaldehyde in vivo remains a mystery. In vitro, doxorubicin reacts withformaldehyde to give firstly a monomeric oxazolidine, doxazolidine, and secondly a dimeric oxazolidine,doxoform. Doxorubicin reacts with formaldehyde in the presence of salicylamide to give the N-Mannich baseconjugate, doxsaliform. Doxsaliform is several fold more active in tumor cell growth inhibition than doxorubicin,but doxazolidine and doxoform are orders of magnitude more active than doxorubicin. Exploratory researchon the potential for doxsaliform and doxazolidine as targeted cytotoxins is presented. A promisinglead design is pentyl PABC-Doxaz, targeted to a carboxylesterase enzyme overexpressed in liver cancercells and/or colon cancer cells.

Oxazolidinium compounds and use as hydrate inhibitors

Abstract: Oxazolidinium compounds are formed by the reaction of a halohydrin or an epoxide with a secondary amine and an aldehyde or a ketone. The oxazolidinium compounds are formed directly and do not require the reaction of a pre-formed oxazolidine with an alkylating agent. The compounds are useful as gas hydrate inhibitors in oil and gas production and transportation.

Kinetic and thermodynamic control of axial chirality in biaryl-derived fused oxazolidine lactams exploiting a centre-axis relay of unit efficiency

Abstract: The condensation of a 2-substituted-2-aminoethanol with methyl 2′-formylbiphenyl-2-carboxylate produces only two of the four possible axially chiral 6,7-dihydrodibenz[c,e]oxazolo[3,2-a]azepin-9(4bH)-ones (fused oxazolidine lactams), with kinetically controlled diastereoisomer ratios of up to 96 : 4. Within each lactam product the central chirality of the oxazolidine-fused benzylic position C(4b) is relayed to the biaryl axis with unit efficiency, the mis-matching of these stereogenic elements being prohibited due to strain, as predicted by molecular mechanics calculations. Diastereoisomeric lactam pairs can be equilibrated by heating with acid, and under these thermodynamic conditions reversed diastereoisomer ratios of up to 26 : 74 are observed.

Novel combination tanning using diphenols and oxazolidine for high stability leather

Abstract: Leather tanning reactions between collagen and dihydroxynaphthalenes (DHNs) or diphenols and oxazolidine have been investigated using hide powder and sheepskin pickled pelt This investigation showed that some DHNs have a tanning effect on collagen The measurement of combined and cross-linked DHNs on collagen showed that 30-40% 1,6- and 2,6-DHNs were fixed through covalent bonding Shrinkage temperature of the leather changed little after the non combined DHNs had been removed from the leather, indicating that the high stability of the combination tanned leather comes from the covalent bonding formed between DHNs and collagen through oxazolidine

A Novel Oxazolidine Linker for the Synthesis of Peptide Aldehydes

Abstract: A reliable method for solid-phase synthesis of peptide aldehydes by using a new oxazolidine linker is described. Based on a comparative study using the usual cleavage protocol as is used for the Fmoc-based peptide synthesis, we found that this new linker is more appropriate for the synthesis of peptide aldehydes compared with the precedent acetal, semicarbazone or threonine linker. Whereas N-Acylated oxazolidines might be partially deprotected to non-N-acylated intermediates in the TFA cocktail containing several soft nucleophiles which cause significant side reactions, the new oxazolidine linker could produce the desired peptide aldehydes by simple Et2O washing and subsequent aqueous workup in high chemical yields and purity. We demonstrate the new method is useful especially for the preparation of highly functionalized long-chain peptide aldehydes which require several scavenger chemicals in the final deprotection step.

A Novel Oxazolidine Linker for the Synthesis of Peptide Aldehydes

Abstract: A reliable method for solid-phase synthesis of peptide aldehydes by using a new oxazolidine linker is described. Based on a comparative study using the usual cleavage protocol as is used for the Fmoc-based peptide synthesis, we found that this new linker is more appropriate for the synthesis of peptide aldehydes compared with the precedent acetal, semicarbazone or threonine linker. Whereas N-Acylated oxazolidines might be partially deprotected to non-N-acylated intermediates in the TFA cocktail containing several soft nucleophiles which cause significant side reactions, the new oxazolidine linker could produce the desired peptide aldehydes by simple Et2O washing and subsequent aqueous workup in high chemical yields and purity. We demonstrate the new method is useful especially for the preparation of highly functionalized long-chain peptide aldehydes which require several scavenger chemicals in the final deprotection step.

Synthesis and thermal crosslinking of oxazolidine-functionalized polyurethanes

Abstract: A new oxazolidine derivative was obtained from phenol, 2-amino-2-methylpropane-1,3-diol and paraformaldehyde. The reaction of this novel oxazolidine diol with phenylisocyanate lead to a urethane model compound which can be polymerized thermally by oxazolidine ring opening to give a Mannich bridge structure. Linear segmented polyurethanes were prepared by reaction of different ratios of oxazolidine diol and commercial polyethylenglycol (M w ∼ 400) with 4,4'-methylenbis (cyclohexylisocyanate) (HMDI, 90% isomers mixture). The polyurethanes were thermally characterized and crosslinked by oxazolidine ring opening to obtain materials which showed improved thermal stability.

Synthesis of 2 -phenyl -3 -hydroxyethanyl -1,3 -oxazolidine and its application as latent curing agents

Abstract: A kind of new compound of 2-phenyl-3-hydroxyethanyl-1,3-oxazolidine was successfully synthesized by addition–condensation reaction of phenyl aldehyde and β-hydroxylethanolamine and purified by vacuum distillation. Its purity was examined by gas chromatographic analysis. Its structure was confirmed by 13C NMR and FTIR. When this compound was added as a latent curing agent in single-component moisture-curable polyurethane system (SPU), bubbles of SPU formed during curing was obviously restrained, and the elongation at break of the cured SPU contained a certain content of 2-phenyl-3-hydroxyethanyl-1,3-oxazolidine was increased to 16 times when compared with that uncontained this oxazolidine derivative. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007

Method of preparation of anticancer taxanes using 3-[(substituted-2-trialkylsilyl)ethoxy-carbonyl]-5-oxazolidine carboxylic acids

Abstract: This invention relates to a process for preparation of taxanes comprising subjecting 7,10-diprotected intermediates 7-O-(2-haloacyl)baccatin III 6c or 7,10-O-di-(2-haloacyl)-10-deacetylbaccatin III 6b to a step of coupling with (4S,5R)-3-[(2-alkyl/aryl-2-trialkylsilyl)ethoxy-carbonyl]-4-aryl-2-substituted-1,3-oxazolidine-5-carboxylic acid 1 in the presence of a condensation agent, an activating agent and an aromatic hydrocarbon to obtain 7-O-[2-(haloacyl)]-13-[(4S,5R)-4-aryl-2-substituted-3(2-unsubstituted/substituted-2-trialkylsilyl)-ethoxycarbonyl-1,3-oxazolidinyl-5-carbonyl]baccatin III 7a or 7,10-di-O [2-(haloacyl)]-13-[(4S,5R)-4-aryl-2-substituted-3-(2-unsubstituted/substituted-2-trialkylsilyl)ethoxy-carbonyl-1, 3-oxazolidinyl-5-carbonyl]-10-deacetylbaccatin III 7b; treating the coupled products 7-O-[2-(haloacyl)]-13-[(4S,5R)-4-aryl-2-substituted-3-(2-substituted-2-trialkylsilyl)ethoxy-carbonyl-1, 3-oxazolidinyl-5-carbonyl]baccatin III 7a or 7,10-di-O-[2[(haloacyl)]-13-[(4S,5R)-4-aryl-2-substituted-3-(2-substituted-2-trialkylsilyl)ethoxycarbonyl-1, 3-oxazolidinyl-5-carbonyl-10-deacetylbaccatin III 7b with tetraalkylammonium halide in a haloalkane to obtain free amine of structure 8; treating free amine 8 with acid chloride or acid anhydride in the presence of a base in a heterogeneous phase to obtain the intermediates of structure 9; subjecting the intermediates of compound 9 to the deprotection of 2-haloacyl group under mild alkaline condition at −20 to +40° C. for 6-24 h in the presence of ammonia or aliphatic amines or aromatic amines or their combination to obtain paclitaxel or docetaxel.

Cyclization of vinyl ethers derived from amino alcohols

Abstract: Cyclization of vinyl ethers derived from linear and cyclic α- and β-amino alcohols, catalyzed by mercury(II) acetate gave 2-methyloxazolidines and 2-methylperhydro-1,3-oxazines in 37–94% yield.

tert‐Butyl 2,2‐dimethyl‐4‐(3‐phenyl‐2,5‐dihydro­furan‐2‐yl)oxazolidine‐3‐carboxyl­ate

Abstract: The title compound, C20H27NO4, is a synthetic intermediate towards the preparation of novel furanomycin derivatives. Its structure is consistent with the assumed anti selectivity of the allenylation step. Comment The title compound, (I), is a synthetic intermediate in the construction of novel furanomycin derivatives using the gold- catalysed cyclization of � -hydroxyallenes (Hoffmann-Roder & Krause, 2001). The allene precursor is obtained by diastereoselective allenylation of Garner's Aldehyde (Garner & Park, 1987) with � -phenylpropargyl bromide mediated by indium (Erdsack & Krause, 2007). A crystal structure deter- mination of (I) has now been carried out to establish the relative configurations of the stereogenic centers at the dihydrofuranyl ring to prove the anti selectivity of the alle- nylation step. Fig. 1 shows that the relative configuration of C10 and C11 is as expected. The torsion angle C7—C10— C11—N1 is � 178.30 (14) � . The configurations of the chiral C atoms in (I) (C10 R and C11 S) were assigned based on those of the equivalent atoms in the known starting materals.

Oxazolidine compound for synthesizing taxone pharmaceutical side-chain and preparation method thereof

Abstract: This invention relates to a method for preparing oxazolidine side chain ester of taxanes kind medicines with chiral mellow such as natural menthol and synthesized chiral mellows, which first of all esterifies natural or synthesized chiral mellows with acyl chloride and then shrink with benzaldehyde under a certain condition to get a chiral epoxy compound, which is synthesized in several times to get the product of oxazolidine side chain ester for preparing taxanes kind medicines.

Efficient Oxidative Conversion of Aldehydes to 2‐Substituted Oxazolines and Oxazines Using (Diacetoxyiodo)benzene.

Abstract: An efficient synthesis of 2-substituted oxazolines from aldehydes and 2-amino alcohol using (diacetoxyiodo)benzene as an oxidant, is reported. (Diacetoxyiodo)benzene acts as a mild dehydrogenating agent to convert the initially formed oxazolidine from aldehyde and 2-amino alcohol to furnish 2-substituted oxazoline. Similarly, 3-aminopropanol and aldehydes gives the corresponding 2-substituted oxazines.

The 3-[3α(2α-Hydroxy)pinane]-4,5-(pinan)-1,3-oxazolidine Synthesis, Structure and Properties

Abstract: The new pinane derivative containing unique multifused ring system was synthesized. The crystal, molecularand electronic structure of the title compound has been determined. Both pinane ring systems have the sameconformation. The five-membered oxazolidine ring exists in twisted chair conformation. The structure isexpanded through O-H O hydrogen bond to semiinfinite hydrogen-bonded chain. The bond lengths andangles in the optimised structure are si milar to the experimental ones. The CH

(E)‐N‐(1,3‐Oxazolidin‐2‐ylidene)benzamide

Abstract: The aryl and oxazolidine rings in the title compound, C10H10N2O2, are essentially coplanar [dihedral angle = 3.8 (6)°]. The crystal structure involves intra- and intermolecular N—H⋯O hydrogen bonds.

Method for producing imine compound or oxazolidine compound

Abstract: PROBLEM TO BE SOLVED: To provide a method for producing an imine compound or oxazolidine compound in high purity SOLUTION: The method for producing the imine compound or oxazolidine compound comprises the step of carrying out a reaction between an amine compound (a) and a carbonyl compound (b) in the presence of (B) a compound liquid at 23°C and reactive to water but inert to the amine compound (a), wherein the compound B may contain at least one element selected from silicon, titanium, zirconium, tin, zinc and aluminum, and preferably contains a hydrocarbon-oxy group COPYRIGHT: (C)2007,JPO&INPIT

Oxazolidine derivates, preparation and application thereof

Abstract: The invention discloses an oxazolidine derivative shown as A, B or C and a salt, a solvate, an optical isomer or a polymorphic substance and a medical composite which are acceptable in pharmacology, wherein R0 represents H or alkyl of C1 to C4; R1 represents H, halogen, alkyl of C1 to C4, alkoxy of C1 to C4 or morpholinyl; R2 represents H or halogen; R3 represents H or alkyl of C1 to C4; and X represents CH or N. The invention also discloses a preparation method thereof and an application of the oxazolidine derivative to the preparation of medicines for treating bacterial infectious diseases. The compound has the antibiosis function superior to the prior medicine of LBM-415 and has higher application value in the medical field.

Intramolecular Chiral Relay at Stereogenic Nitrogen: Oxazolidine Catalysts Derived from Ephedra Alkaloids.

Abstract: A series of oxazolidines have been prepared by reaction of either (1 R ,2 S )-ephedrine or (1 S ,2 S )-pseudoephedrine with salicylaldehyde derivatives. The resultant oxazolidines were used as catalytic ligands in the addition of diethylzinc to a variety of aromatic and aliphatic aldehydes. It was determined that the (1 R ,2 S )-ephedrine based oxazolidine derivative 9 gave the highest enantioselectivities.