Glucosamine derived DISAL donors for stereoselective glycosylations under neutral conditions

DISAL (methyl 3,5-dinitrosalicylate) d-glucosyl, d-galactosyl, d-mannosyl, and l-quinovosyl donors have previously provided the efficient glycosylation of a range of substrates under either strictly neutral, mildly basic, or very mildly Lewis acidic (LiClO₄) conditions. Herein we report the synthesis of new glucosamine DISAL donors, carrying N-TCP, -Troc, or -TFAc protecting groups, and their use in β-(1,2-trans) selective glycosylations, primarily in NMP in the absence of any added Lewis acids, or in CH₃NO₂ with LiClO₄. Finally, precise microwave heating proved effective in promoting the difficult glycosylation of the 3-OH of a glucosamine derivative.     

Pre-activation based stereoselective glycosylations: Stereochemical control by additives and solvent

Stereochemical control is an important issue in carbohydrate synthesis.Glycosyl donors with participating acyl protective groups on 2-O have been shown to give 1,2-trans glycosides reliably under the pre-activation based reaction condition.In this work,the effects of additives and reaction solvents on stereoselectivity were examined using donors without participating protective groups on 2-O.While several triflate salt additives did not have major effects,the amount of AgOTf was found to significantly impac...     

A general,highly stereoselective synthesis of amines

The stereochemical course of cycloalkanone imine reductions by a variety of boron hydride reagents is described; very high stereoselectivity with substituted alkali metal borohydrides is reported.     

A double regio- and stereoselective glycosylation strategy for the synthesis of N-glycans

A building block approach for biantennary N-linked oligosaccharides from glycoproteins (N-glycans) has been developed. Starting from a core trisaccharide (beta-mannosyl chitobiose) containing a benzylidene-protected beta-mannoside, the attachment of the disaccharide building blocks for the antennae can be performed in a double regio- and stereoselective manner. A short synthesis of a GlcNPhtbeta1,2Man donor was developed. The benzylidene acetal moiety, as a minimal protection of the beta-mannoside, allows selective alpha-glycosylation at OH-3 of the 2,3-diol with GlcNbeta1,2Man trichloroacetimidate donors. Subsequent debenzylidenation leads to a 4,6-diol, which can be selectively extended at OH-6. Overreaction at OH-4 was generally low when phthalimido-protected donors were used. This general strategy represents a modular synthesis of N-glycans and their glycoconjugates.     

A general and stereoselective method for synthesis of tri- and tetrasubstituted alkenes

A convenient, general and stereoselective synthesis of trisubstituted alkenes and tetrasubstituted alkenes containing a cyanide function as well as trisubstituted episulphides have been elaborated. Methodology described for the preparation of these compounds is based on the corresponding readily available selenophosphates 1 and thiophosphates 2.     

A new strategy for the stereoselective synthesis of 2,2′-bipyrrolidines

A new strategy for the stereoselective synthesis of the 2,2′-bipyrrolidine scaffold is presented using a metathesis reaction followed by asymmetric dihydroxylation for the introduction of the stereogenic elements. This straightforward high-yielding process is suitable for application to the synthesis of additional heterocycles.     

A new strategy for the stereoselective synthesis of 2,3-dideoxy-3-fluoro-D-ribofuranose derivatives

The important intermediate for syntheses of various anti-HIV nucleoside analogues, methyl 2,3-dideoxy-3-fluoro-6-O-(p-methylbenzoyl)-a-D-ribofuranoside, was synthesized starting from 2-deoxy-D-ribose in 5 steps with an overall yield of 24%. This strategy can be also used for synthesizing other analogues with various substitutions at 3-C position.     

A general synthetic strategy for oxide-supported metal nanoparticle catalysts

Despite recent exciting progress in catalysis by supported gold nanoparticles, there remains the formidable challenge of preparing supported gold catalysts that collectively incorporate precise control over factors such as size and size-distribution of the gold nanoparticles, homogeneous dispersion of the particles on the support, and the ability to utilize a wide range of supports that profoundly affect catalytic performance. Here, we describe a synthetic methodology that achieves these goals. In this strategy, weak interface interactions evenly deposit presynthesized organic-capped metal nanoparticles on oxide supports. The homogeneous dispersion of nanoparticles on oxides is then locked in place, without aggregation, through careful calcination. The approach takes advantage of recent advances in the synthesis of metal and oxide nanomaterials and helps to bring together these two classes of materials for catalysis applications. An important feature is that the strategy allows metal nanoparticles to be well dispersed on a variety of oxides with few restrictions on their physical and chemical properties. Following this synthetic procedure, we have successfully developed efficient gold catalysts for green chemistry processes, such as the production of ethyl acetate from the selective oxidation of ethanol by oxygen at 100 degrees C.     

A general strategy for the synthesis of azapeptidomimetic lactams

A selection of azapeptidomimetics containing constraining lactam rings have been prepared by Mitsunobu cyclization of serine/homologated serine-azaalanine derivatives. These include sterically-congested β-lactams, as well as γ-butyrolactam and δ-valerolactam analogs. A novel azaamino acid acylation method was developed to prepare the sterically demanding α-benzyl-serine-azaalanine precursor. In all cases, the Mitsunobu conditions were highly efficient in forming the desired azapeptidomimetic lactams. The reported process represents a general strategy for the synthesis of peptidomimetic structures with a constraining lactam ring.     

New strategy for the stereoselective synthesis of fluorinated beta-amino acids

Racemic and chiral nonracemic alpha-substituted and alpha-unsubstituted beta-fluoroalkyl beta-amino acid derivatives 6 and 9 have been synthesized in two steps starting from fluorinated imidoyl chlorides 1 and ester enolates. This approach is based on the chemical reduction of previously obtained gamma-fluorinated beta-enamino esters 4 by using ZnI(2)/NaBH(4) in a nonchelated aprotic medium (dry CH(2)Cl(2)) as the reducing agent. A metal-chelated six-membered model has been suggested to explain the stereochemical outcome of the reduction reaction. The process takes place with high yields and with moderate to good diastereoselectivity. The best results related to diastereoselective reduction of chiral beta-enamino esters 4 were provided by the use of (-)-8-phenylmenthol as a chiral auxiliary.     

A general strategy for creating "inactive-conformation" abl inhibitors

Kinase inhibitors that bind to the ATP cleft can be broadly classified into two groups: those that bind exclusively to the ATP site with the kinase assuming a conformation otherwise conducive to phosphotransfer (type I), and those that exploit a hydrophobic site immediately adjacent to the ATP pocket made accessible by a conformational rearrangement of the activation loop (type II). To date, all type II inhibitors were discovered by using structure-activity-guided optimization strategies. Here, we describe a general pharmacophore model of type II inhibition that enables a rational "hybrid-design" approach whereby a 3-trifluoromethylbenzamide functionality is appended to four distinct type I scaffolds in order to convert them into their corresponding type II counterparts. We demonstrate that the designed compounds function as type II inhibitors by using biochemical and cellular kinase assays and by cocrystallography with Abl.     

A general thermolabile protecting group strategy for organocatalytic metal-organic frameworks

We present a general strategy for incorporating organocatalytic moieties into metal-organic frameworks (MOFs). The organocatalytic units are protected by a thermolabile protecting group during MOF synthesis and then unveiled by a simple postsynthetic heating step. The strategy is exemplified using a thermolabile tert-butoxycarbonyl (Boc) protecting group for a proline moiety, the removal of which endows the resulting cubic zinc(II) IRMOF with catalytic activity for asymmetric aldol reactions. The bulky Boc groups also prevent framework interpenetration, producing open MOFs that can admit relatively large substrates.     

A general precipitation strategy for large-scale synthesis of molybdate nanostructures

A general precipitation strategy has been developed for the large-scale synthesis of molybdate nanostructures, and a series of molybdate nanostructures such as Fe(2)(MoO(4))(3) nanoparticles, ZnMoO(4) nanoplates, MnMoO(4) nanorods and CoMoO(4) nanowires have been successfully prepared.     

A new strategy for the regio- and stereoselective hydroxylation of trans-2-aminocyclohexenecarboxylic acid

A simple and novel method for the introduction of an extra hydroxy group into an aminocyclohexanecarboxylic acid via stereoselective epoxidation and regioselective opening of the oxirane ring is presented. This method permits the preparation of the enantiomerically pure hydroxylated amino acid.     

A general stereoselective method for the synthesis of cyclopropanecarboxylates. A new version of the homologous Horner-Wadsworth-Emmons reaction

The synthesis of alpha-, beta- and gamma-substituted alpha-phosphono-gamma-lactones was accomplished using different ring closure and ring homologation strategies. It was found that the lactones could be selectively transformed into the corresponding ethyl cyclopropanecarboxylates by treatment with sodium ethoxide in boiling THF. The reported reaction provides an attractive alternative to the classical homologous Horner-Wadsworth-Emmons approach to the construction of cyclopropanes with electron-withdrawing functionalities.     

A general strategy for the rational design of size-selective mesoporous catalysts

A series of functionalized mesoporous silicas with cagelike pore topology has been synthesized and screened for size-selective catalytic transformations. The aluminum-catalyzed Meerwein-Ponndorf-Verley (MPV) reduction of differently sized aromatic aldehydes (benzaldehyde and 1-pyrenecarbox-aldehyde) has been investigated as a test reaction. The catalysts were synthesized in a two-step grafting sequence comprising pore-size engineering of mesoporous silicas (SBA-1, SBA-2, SBA-16) with long-chain alkyl dimethylaminosilanes and surface organoaluminum chemistry with triethylaluminum [{Al(CH(2)CH(3))3}2]. Size-selective reaction behavior was found for small pore SBA-1 materials, and the selectivity could be efficiently tuned by selecting a silylating reagent of appropriate size. The results are compared with the catalytic performance of a large-pore periodic mesoporous organosilica PMO[SBA-1] and the nonporous high-surface-area silicas Aerosil 300/380.     

Glycosyl sulfonium ions as storable intermediates for glycosylations

Glycosyl sulfonium ions, which serve as persistent glycosyl cation equivalents, were prepared by the addition of diorganosulfides to an electrochemically generated glycosyl triflate. Low-temperature and variable-temperature NMR studies were performed to reveal the structure, stability, and reactivity of glycosyl sulfonium ions. The glycosyl sulfonium ions could be used as storable intermediates for reactions with various glycosyl acceptors including thioglycosides to give the corresponding disaccharides.     

A stereoselective intramolecular Diels-Alder strategy for the tricyclo[9.3.1.0]pentadecane core of aromatic C-ring taxanes

A stereoselective Lewis acid-catalyzed and chelation controlled intramolecular Diels-Alder entry into the tricyclo[9.3.1.0^3,8]pentadecane core of aromatic C-ring taxanes is described. The approach affords an efficient, high yield, access to aromatic C-ring taxanes variably functionalized at the C2, C4, C5, and C9 positions.