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SYNTHESIS OF THE METHYL alpha-GLYCOSIDE OF THE INTRACATENARY DISACCHARIDE REPEATING UNIT OF THE O-POLYSACCHARIDE OF VIBRIO CHOLERAE O:1. A COMPARISON OF TWO ASSEMBLY STRATEGIES

The two strategies engaged in the construction of the title disaccharide 17 comprise: 1. assembly of a diamino disaccharide and its N-acylation using chiral reagents to introduce the 4-(3-deoxy-L-glycero-tetronyl) group, followed by deprotection, and 2. preparation of a glycosyl acceptor and a glycosyl donor both having the chiral 3-deoxy-L-glycero-tetronamido group already in place, their condensation to give a fully substituted disaccharide, and deprotection.Accordingly, the crystalline diamino disaccharide methyl 2-O-(4-amino-3-O-benzyl-4,6-dideoxy-alpha-D-mannopyranosyl)-4-amino-3-O-benzyl-4,6-dideoxy-alpha-D-mannopyranoside, (14), was prepared from the known diazido disaccharide 12, and treated with the lactone 30, or its acetylated or benzylated analogs 31 and 32, respectively, as the N-acylating reagents.Subsequent deprotection of the respective products applying standard chemistry gave 17.Alternatively, the methyl alpha-glycoside of the monomeric intracatenary repeating unit of Vibrio cholerae O:1 (2) was converted to the fully benzoylated glycosyl chloride 26, and the latter glycosyl donor was condensed with methyl 3-O-benzyl-4,6-dideoxy-4-(2,4-di-O-benzoyl-3-deoxy-L-glycero-tetronamido)-alpha-D-mannopyranoside (24), to give the corresponding, fully protected derivative 27.Deprotection then readily gave 17.It appears that the title disaccharide can be most efficiently synthesized using synthons 24 and 26.The lactones 30 and 32 appear to be promising acylating reagents for the introduction of the 3-deoxy-L-glycero-tetronamido group when higher oligosaccharides in this series will be synthesized via their (poly)amino precursors.

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Characterisation of inorganic elements and volatile organic compounds in the dried sea cucumber Stichopus japonicus

The sea cucumber Stichopus japonicus lives in a variety of marine habitats and is an important cultivated edible aquatic species in East Asia. In this study, S. japonicus, collected from the sea near Jeju Island of Korea, was lyophilised or vacuum-dried and then analysed by gas chromatography-mass spectrometry (GC-MS) or inductively coupled plasma mass spectrometry (ICP-MS). The GC-MS profiles of vacuum-dried and lyophilised samples differed. Based on direct injection and static headspace analysis, 37 volatile organic compounds (VOCs) were identified in vacuum-dried samples and 33 VOCs were identified in lyophilised samples. Therefore, the odour of vacuum-dried sea cucumber is thought to be due to the presence of various VOCs that are absent in lyophilised sea cucumber. According to ICP-MS analysis, the levels of 15 inorganic elements were slightly higher in lyophilised samples than in vacuum-dried samples. The results of the inorganic and organic chemical analyses provide information about the composition of dried sea cucumber.

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Stereoselective synthesis of 12,13-cyclopropyl-epothilone B and side-chain-modified variants

A general strategy has been devised for the stereoselective synthesis of 12,13-cyclopropyl-epothilone B and side-chain-modified variants thereof, which relies on late stage introduction of the heterocycle through Wittig olefination of ketone 14. Formation of the macrocycle was achieved through RCM-based ring closure and introduction of the cyclopropane moiety involved a highly selective Charette cyclopropanation of allylic alcohol 7.

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17beta-2-oxo-tetrahydrofuranyl)-carbothioic acid ester, -carboxylic acid ester and -carboxylic acid amide androstane derivatives

Compounds of the androstane series are described having general formula and solvates thereof, in which R1 represents O, S or NH; R2 individually represents OC(=O)C1-6 alkyl; R3 individually represents hydrogen, methyl (which may be in either the alpha or beta configuration) or methylene; or R2 and R3 together represent where R6 and R7 are the same or different and each represents hydrogen or C1-6 alkyl; R4 and R5 are the same or different and each represents hydrogen or halogen and represents a single or a double bond. These compounds and their solvates have use in medicine as anti-inflammatory or anti-allergic agents.

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Studies towards the total synthesis of (-)-caulerpenynol, a toxic sesquiterpenoid of the green seaweed caulerpa taxifolia

The first diastereoselective synthesis of the antimicrobial and cytotoxic agent (-)-caulerpenynol (2) was achieved in relatively few steps from, commercially available (S)-malic acid, Highlights of this synthesis include the nonracemization. of the sensitive a-hydroxy ketone moiety and the proper choice of the protecting groups for critical last deprotection step. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009.

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Kinetic resolution of racemic 2-hydroxy-gamma-butyrolactones by asymmetric esterification using diphenylacetic acid with pivalic anhydride and a chiral acyl-transfer catalyst

Various optically active 2-hydroxy-gamma-butyrolactone derivatives are produced via the kinetic resolution of racemic 2-hydroxy-gamma-butyrolactones with diphenylacetic acid using pivalic anhydride and (R)-benzotetramisole ((R)-BTM), a chiral acyl-transfer catalyst. Importantly, the substrate scope of this novel protocol is fairly broad (12 examples, s-value; up to over 1000). In addition, we succeeded in disclosing the reaction mechanism to afford high enantioselectivity using theoretical calculations and expounded on the substituent effects at the C-3 positions in 2-hydroxylactones.

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Multi-step application of immobilized reagents and scavengers: A total synthesis of epothilone C

The total synthesis of the cytotoxic antitumour natural product epothilone C has provided a stage for the exploitation and further development of immobilized reagent methods. A stereoselective convergent synthetic strategy was applied, incorporating polymer-supported reagents, catalysts, scavengers and catch-and-release techniques to avoid frequent aqueous work-up and chromatographic purification.

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Total synthesis of (+)-brasilenyne. Application of an intramolecular silicon-assisted cross-coupling reaction

The first enantioselective total synthesis of (+)-brasilenyne (1) has been achieved in 19 linear steps, with 5.1% overall yield from L-(S)-malic acid. The construction of the oxonin core containing a 1,3-cis, cis diene unit was accomplished with a tandem ring-closing metathesis/silicon-assisted intramolecular cross-coupling reaction. In addition, a key propargylic stereogenic center was created through a novel, highly diastereoselective ring opening of a 1,3-dioxolanone promoted by TiCl4. This reaction proceeded through an oxocarbenium ion intermediate and the asymmetric induction was fully controlled by L-malic acid residue. The C(8) stereogenic center was set by a reagent-controlled asymmetric allylboration.

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Flexible routes to the 5-hydroxy acid fragment of the cryptophycins

Two solutions to establishing the anti stereochemistry of the vicinal stereocenters in the 5-hydroxy acid subunit of cryptophycin, based on initial Evans syn aldol reactions between an N-(propionyl)oxazolidinone 4 and a C3 aldehyde, were developed. In the first route, the secondary hydroxy group was inverted by use of Mitsunobu reaction conditions, whereas the second route features an inversion of the methyl-bearing stereocenter, achieved by reductive removal of the chiral auxiliary, elimination to afford the terminal alkene, and anti-selective hydroboration. The aryl part can be attached either by Wittig-Horner olefination or by a modified Julia coupling. Both routes provide the hydroxy acid 16 in a very efficient manner. The substrate for the hydroboration, alkene 22, could also be obtained from (S)-malic acid. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.

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PROCESS FOR THE HYDROGENATION OF ESTERS OF ALPHA-SUBSTITUTED CARBOXYLIC ACIDS

There is provided a process for the hydrogenation of esters of alpha-substituted carboxylic acids which comprises reacting an ester of an alpha-substituted carboxylic acid with hydrogen in the presence of a catalyst under substantially homogeneous supercritical conditions. Preferably, the ester of an alpha-substituted carboxylic acids is an ester of formula (1): wherein: R1 and R2are each independently an optionally substituted hydrocarbyl group or an optionally substituted heterocyclic group; and Y is a heteroatom or an optionally substituted heteroatom group. More preferably, the ester of an alpha-substituted is carboxylic acids is an ester of formula (2): wherein: R3 is an optionally substituted hydrocarbyl group or an optionally substituted heterocyclic group; R4and R5 are each independently hydrogen, an optionally substituted hydrocarbyl group or an optionally substituted heterocyclic group; Y is a heteroatom or an optionally substituted heteroatom group; Q is a functional group; and n 1. Most preferably, the ester of an alpha-substituted carboxylic acids is an ester of formula (3): wherein: R3 and R6 are each independently an optionally substituted hydrocarbyl group or an optionally substituted heterocyclic group; R4 and R5 are each independently hydrogen, an optionally substituted hydrocarbyl group or an optionally substituted heterocyclic group; Y is a heteroatom or an optionally substituted heteroatom group; and n 1.

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