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Two strategies for the projected total synthesis of the phenomenally potent antitumour macrolides amphidinolide N (1) and caribenolide I (2) are described. The title compounds are introduced as challenging and unique targets for chemical synthesis, and their retrosynthetic analysis is presented. The synthesis of the four defined key building blocks (10, 39, 67 and 72), required for the construction of amphidinolide N (1), in their enantiomerically pure forms, is described, followed by the coupling of 10, 39 and 72 through hydrazone alkylation processes to generate the complete C6-C29 carbon framework of the target compound (1). Fusion of the remaining C1-C5 sector (72) onto the molecule by metathesis-based methods was unsuccessful, resulting in the adoption of a second-generation strategy which called for the employment of one of the array of palladium-catalysed cross-coupling reactions to generate the C5-C6 carbon-carbon bond. Vinyl bromide 125, representing the C6-C29 skeleton of caribenolide I (2), was prepared through the sequential alkylation of hydrazone 10 with bromide 116 and iodide 55, but failed to engage in the appropriate cross-coupling reaction with a variety of C1-C4 partners. Despite these setbacks, the information gleaned from these endeavours was to prove invaluable in laying the foundation for the eventual successful approach to the macrocyclic structures of amphidinolide N (1) and caribenolide I (2). The Royal Society of Chemistry 2006.

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A high energy conformation, in which the adenine moiety of adenosine 2′-phosphate occupies a C-1′-axial ribofuranosyl position, is stabilised through the chelation of a second (additional) Mg2+ ion by the 2′- and furanose ring O-atoms; with inositol 1-phosphate as the substrate, the 1- and 6-O-atoms chelate the second Mg2+ ion and for both substrates a different (buried) Mg2+ ion interacts directly with the phosphate moiety.

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Diastereoselectivity of 1,3-dipolar cycloaddition reactions of benzyl azide, diazomethane, a nitrile oxide and a nitrile imine to alpha-methylidene-gamma-lactone dipolarophile was effectively controlled by a bulky gamma-substituent, 4-methyl-2,6,7-trioxabicyclo[2.2.2]octan-1-yl in gamma-position of the dipolarophile. The dipoles added from the less hindered face of the double bond with an excellent selectivity. Enantiomerically pure dipolarophile was prepared from the easily available (S)-5-oxotetrahydrohydrofuran-2-carboxylic acid.

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A general strategy that permits the stereocontrolled construction of acyclic chains containing vicinal and/or alternating alkyl and hydroxy substituents is presented.Structural subunits of ionomycin were synthesized from a common chiral intermediate.

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According to the present invention an enantiopure chelating compound of general Formula 10A or 10B is provided: wherein each of R1 through R3 is independently selected hydrogen, substituted or unsubstituted C1-C20 alkyl, substituted or unsubstituted C2-C20 alkenyl, substituted or unsubstituted C2-C20 alkynyl, substituted or unsubstituted C3-C10 cycloalkyl, substituted or unsubstituted C6-C60 aryl, or -Si(R4)(R5)(R6), and each of R4 through R6 is independently selected a substituted or unsubstituted group consisting of C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C1-C20 alkoxy, C3-C10 cycloalkyl, C6-C60 aryl, and C6-C60 aryloxy. The present invention further refers to a corresponding preparation method of the chelating compound and chelator coupled pharmaceuticals including the same.

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Enantiomerically pure 4-methyl-tetrahydro-5-oxo-2-furancarboxylic acids and esters are prepared by enzymatic resolution of the chiral racemic esters. Their stereochemistry as well as their absolute configurations have been established by chemical correlation. The influence of the alkoxycarbonyl group at C-2 and that of the methyl group at C-4 on the sign of the Cotton effect in their CD spectra have been investigated. Formation of enantiomerically pure hydroxydiesters, precursors of the above-mentioned gamma- lactones, by baker’s yeast reduction of the corresponding ketodiesters was unsatisfactory. (C) 2000 Elsevier Science Ltd.

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Samples of (R)- and (S)-<2-2H>cadaverines 10 and 12 prepared from L and D-glutamic acid, respectively, were fed to Lupinus luteus plants and the labelling patterns in lupinine 1 determined by 2H NMR spectroscopy demonstrated that the quinolizidine ring system is formed by removal of the pro-S hydrogen and retention of the pro-R hydrogen at C-1 of lupinine.

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Starting from Boc-protected tryptamine and (S)-tetrahydro-5-oxo-2- furancarboxylic acid, facile enantioselective total synthesis of desbromoarborescidines A-C and the formal synthesis of (S)-deplancheine have been accomplished via a common intermediate (S)-indolo[2,3-a]quinolizine. Synthesis of enantiomerically pure (S)-acetoxyglutarimide, stereoselective reductive intramolecular cyclization, hydroxyl group-assisted in situ N-Boc-deprotection, selective deoxygenation of the xanthate ester, and lactam hydrolysis followed by an appropriate exchange of nitrogen regioselectivity in intramolecular cyclization were the decisive steps.

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The intense CD bands of marmelo lactones and the related gamma-lactones with unsaturation at the C-5 position were studied in terms of the possible interactions between the n->?* transition of the carbonyl and the ?->?* transition of the double bond at C-5, together with the preferred conformations about the C-4 – C-5 axis.The C-4 – C-5 axis of marmelo lactones takes a preferred conformation which is characteristic for the acyclic allylic alcohols and seems to be an important factor for the (4S)-gamma-lactones with a double bond at the C-5 position to give a negative coupling between the two chromophores.

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Various optically active delta-ketobutanolides were easily prepared in good yields, with an excellent enantiomeric purity, by acylation of organomanganese reagents with the butyrolactone acid chloride 3 prepared from natural (L)-glutamic acid. The reaction takes place in THF under mild conditions (-10C, 3h or 3% CuCl, -30C, 20 min.).

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Tetrahydrofuran – Wikipedia,
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