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A novel chiral silver(I) complex was successfully synthesized from the reaction of chiral (S)-4-isopropylthiazolidine-2-thione ligand (1) with AgOAc in dichloromethane in the presence of Et3N and DMAP at room temperature. Its unique crystal structure was unambiguously disclosed by X-ray analysis. The six silver atoms and six (S)-4-isopropylthiazolidine-2-thione ligands present in the complex are connected through the S and N atoms to form a cluster containing a silver octahedron with six faces of the octahedron capped by ligands. Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002.

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We report a combined experimental and computational study on the cycloadditions of bicyclic 1,3-thiazolium-4-olates, derived from thiazolidin-2-thiones, with asymmetrically-substituted acetylenes. These results provide further mechanistic insights into the above dipolar cycloadditions and enable an unequivocal characterization by NMR spectroscopy of regiochemical patterns as previous derivatives had substituents at both C-2 (in the dipole) and C-6 (in products). Accordingly, new dihydrothiazolopyrid-2-ones have been obtained from a thioisomuenchnone lacking substitution at C-2. With the aim of assessing the steric hindrance as well as the facial stereoselection induced by a bulky group on the Si face (relative to C-7a) of the mesoionic heterocycle, a chiral thioisomuenchnone has also been obtained along with the resulting optically active thiazolopyridones. A computational study of these particular cycloadditions, largely based on an NBO analysis, allowed us to evaluate the influence of substituents on intermolecular steric repulsions, charge transfers, as well as solvent effects.

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The Shocking Revelation of (S)-4-Isopropylthiazolidine-2-thione

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Highly enantioselective chiral aminolysis of cis-4-cyclohexen-1,2-ylenebis(carboxylic acid) anhydride has been performed by employing sodium salt of 4(R)-isopropyl-1,3-thiazolidine-2-thione in THF-DMSO.Other chiral aminolyses of prochiral ?-symmetric dicarboxylic anhydrides such as cis-cyclobutan-1,2-ylenebis(carboxylic acid) anhydride, meso-2,4-dimethylglutaric anhydride, and 3-<(t-butyldimethylsilyl)oxy>glutaric anhydride were similarly investigated.

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A total synthesis of the proposed structure of the natural macrolactone phomolide G (1) by a bidirectional strategy from L-tartaric acid is reported. The omega-terminus of the molecule was elaborated by nitrile extension, C3-alkylation and a substrate-controlled 1,3-ketone reduction. The alpha-terminus was extended by a C2aldehyde-to-alkenal homologation followed by an auxiliary controlled aldol reaction. Macrolactonization and deprotection yielded compound 1 (confirmed by X-ray analysis). This putative structure of phomolide G displayed discordant NMR spectroscopic data in comparison with those of the natural product. Detailed inspection of all NMR spectroscopic data available indicated phomolide G to be likely a diastereomer of 1. The synthetic strategy developed allows control of the absolute stereochemistry at all four chiral secondary alcohol groups. Further manipulation allowed for the preparation of diastereomer 33, the1H and13C NMR spectroscopic data of which are in full accord with that reported for the natural product.

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A diastereoselective synthesis of cycloSal-phosphotriesters (cycloSal=cycloSaligenyl) based on chiral auxiliaries has been developed that allows the synthesis of single diastereomers of the cycloSal-pronucleotides. In previously described synthesis routes, the cycloSal-compounds were always obtained as 1:1 diastereomeric mixtures that could be separated in only rare cases. However, it was shown that the diastereomers have different antiviral activity, toxicity, and hydrolysis stabilities. Here, first a chiral thiazoline derivative was used to prepare nonsubstituted and 5-methyl-cycloSal- phosphotriesters in 48 and ?95%a de (de=diastereomeric excess). However, this approach failed to give the important group of 3-substituted cycloSal-nucleotides. Therefore, two other chiral groups were discovered that allowed the synthesis of (RP)- and (SP)-3-methyl-cycloSal- phosphotriesters as well. The antiviral activity was found to be five- to 20-fold different between the two individual diastereomers, which proved the importance of this approach. Chiral chemical Trojan horses: cycloSal-nucleotides (cycloSal=cycloSaligenyl) of thymidine and cycloSal-pronucleotides of 3?-azido-3?-deoxythymidine (AZT) and 3?-deoxy-2?, 3?-didehydrothymidine (d4T) were prepared by a diastereoselective route for the first time by using a chiral auxiliary approach with up to ?95%a de (see scheme). The procedure is suitable to synthesize cycloSal-phosphotriesters with different substitution patterns in the aromatic residue.

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A convergent stereoselective synthesis of the potent anti-inflammatory, proresolving and neuroprotective lipid mediator protectin D1 (2) has been achieved in 15% yield over eight steps. The key features were a stereocontrolled Evans-aldol reaction with Nagao’s chiral auxiliary and a highly selective Lindlar reduction of internal alkyne 23, allowing the sensitive conjugated E,E,Z-triene to be introduced late in the preparation of 2. The UV and LC/MS-MS data of synthetic protectin D1 (2) matched those obtained from endogenously produced material.

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Titanium enolates from chiral N-propanoyl-1,3-thiazolidine-2-thiones containing bulky substituents at C4 turned out to be excellent platforms to get highly stereocontrolled cross-coupling reactions with acetals. Related oxazolidinethiones also afforded good results, but the corresponding oxazolidinones resulted completely unselective for such reactions, which proves that an exocyclic C{double bond, long}S bond is essential to attain a synthetically useful stereocontrol.

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Pateamine A derivatives and pharmaceutical compositions that include the derivatives. The pateamine A derivatives are alpha-amino pateamine A derivatives that lack the C5-methyl group of pateamine A.

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Starting from readily available (S)-styrene oxide an asymmetric synthesis is described of the naturally occurring anti-HIV spirolactone (-)-hyperolactone C, which possesses adjacent fully substituted stereocenters. The key step involves a stereocontrolled RhII-catalysed oxonium ylide formation-[2,3] sigmatropic rearrangement of an alpha-diazo-beta-ketoester bearing allylic ether functionality. From the resulting furanone, an acid-catalysed lactonisation and dehydrogenation gives the natural product.

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The stereochemical outcome of the Lewis acid-mediated glycolate addition of the titanium enolates from protected N-hydroxyacetyl-4-isopropyl-1,3- thiazolidine-2-thiones to dimethyl and dibenzyl acetals depends on the hydroxyl protecting group. Particularly, the pivaloyl protected glycolate derivative provides the reluctant anti adducts in high yields and diastereomeric ratios, which can be isolated and further converted in enantiomerically pure form to beta-methoxy or beta-benzyloxy alpha-pivaloyloxy carbonyl fragments in a straightforward manner.

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