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Computer-Guided total synthesis of natural products. Recent examples and future perspectives

Quantum chemical calculations of nuclear magnetic resonance (NMR) shifts and coupling constants have been extensively employed in recent years mainly to facilitate structural elucidation of organic molecules. When the results of such calculations are used to determine the most likely structure of a natural product in advance, guiding the subsequent synthetic work, the term ?computer-guided synthesis? could be coined. This review article describes the most relevant examples from recent literature, highlighting the scope and limitations of this merged computational/experimental approach as well.

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Quinuclidine – Wikipedia,
Quinuclidine | C7H724N | ChemSpider

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The reaction rate of a catalyzed reaction is faster than the reaction rate of the uncatalyzed reaction at the same temperature.Recommanded Product: (S)-4-Isopropylthiazolidine-2-thione, Name is (S)-4-Isopropylthiazolidine-2-thione, molecular formula is C6H11NS2, Recommanded Product: (S)-4-Isopropylthiazolidine-2-thione. In a Article, authors is Arbelo Roman, Cristina,once mentioned of Recommanded Product: (S)-4-Isopropylthiazolidine-2-thione

Diastereoselective synthesis of (aryloxy)phosphoramidate prodrugs

The first diastereoselective synthesis of aryloxyphosphoramidate prodrugs of 3?-deoxy-2?,3?-didehydrothymidinemonophosphate (d4TMP) was recently reported. The synthetic approach utilized the chiral auxiliary (S)-4-isopropylthiazolidine-2-thione (2). For this strategy, a stereochemically pure phosphorodiamidate intermediate was needed. The diastereoselective formation of this key compound was investigated by using different phenols and L-alanine methyl or benzyl ester. Generally, the reaction with 3- or 4-substituted phenols led to significantly better diastereoselectivities compared to their 2-substituted counterparts. Moreover, variation of the ester group in the amino acid residue resulted in no significant differences with regard to the obtained diastereoselectivity. From the reported results, a model for the transition state was elaborated. Finally, eight new (S P)-arylphosphoramidates were synthesized with very high diastereoselectivities (up to ? 95 % de) and tested for their anti-HIV potency, showing a tendency for higher antiviral activity from the (S P) diastereomers.

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Diastereoselective addition of chlorotitanium enolates of N-acyl thiazolidinethione to activated imines – A novel synthesis of beta-lactams

We report a novel methodology for preparing enantiomerically pure beta-lactams, starting from nitriles in diastereomeric ratios up to 10:1. The power of the methodology was demonstrated by the efficient synthesis of the cholesterol absorption inhibitor SCH 48462.

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Quinuclidine – Wikipedia,
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Assessing stereoelectronic effects in dipolar cycloadditions yielding fused thiazolopyridone rings

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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Quinuclidine – Wikipedia,
Quinuclidine | C7H723N | ChemSpider

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ALPHA-AMINO PATEAMINE A DERIVATIVES AND METHODS FOR TREATING CHRONIC LYMPHOCYTIC LEUKEMIA

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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Stereoselective and Catalytic Synthesis of anti-beta-Alkoxy-alpha-azido Carboxylic Derivatives

Direct addition of a chiral N-azidoacetyl thiazolidinethione to a variety of dialkyl acetals catalyzed by a commercially available and structurally simple nickel(II) complex gives access in good yields and a highly stereocontrolled manner to anti-beta-alkoxy-alpha-azido carboxylic derivatives which, in turn, can be easily converted into a wide array of enantiomerically pure compounds.

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Chelation-Controlled Chemo-, Regio- and Enantio-Selective Synthesis of Homoallylic Alcohols

Optically active allylic sulphides 10-13, bearing two different leaving groups, react with organocopper reagents by selective substitution of the heterocyclic moiety leading to optically active homoallylic pivalates with chemo-, regio- and enantio-control.This selectivity seems to be related to the coordination exerted by the heterocyclic nucleus towards the organometal.

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Quinuclidine – Wikipedia,
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Lagunamide C is a depsipeptide natural product with low nM cytotoxicity towards numerous cancer cell lines. Synthetically, it is disconnected to a pentapeptide backbone and polyketide unit that possesses four stereogenic centers, of which two of centers are in question (C38 & 40). Our model system highlights a high-selective aldol addition via a Crimmin’s auxiliary setting the C40 ester linkage, and a non-facially selective cyclopropanation with subsequent ring opening for the installation of the C38 methyl center.

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Quinuclidine – Wikipedia,
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Asymmetric Acylation of sec-Alcohols with Twisted Amides Possessing Axial Chirality Induced by the Adjacent Asymmetric Center

This paper reports that axially chiral twisted amides serve as asymmetric acylating agents for sec-alcohols under neutral conditions. Kinetic resolution of various racemic sec-alcohols and desymmetrization of 1,2-, 1,3-, and 1,4-meso-diols were performed by using the twisted amides. The utility of this desymmetrization method was shown by the preparation of the synthetic intermediate 28 for macrolide antibiotic nodusmicin and 18-deoxynargenicin. The stereoselectivity of the acylation reactions is significantly dependent on the bulkiness of both the acyl group and the C-4 substituent of the chiral auxiliary. When an amide possessing an imidazolyl group at C-4 was employed, the stereoselectivity was reversed to give R esters. A possible working model of the acylation reaction is also described on the basis of the structural studies of the twisted amides by IR and 1H and 13C NMR spectroscopies and AMI calculations. These studies suggested that rotamer II is thermodynamically more stable than the others. The rotamer II has an axial chirality about its C(O)-N linkage that is induced by the adjacent chiral center. This would enable discrimination of the two enantiomeric hydroxy groups of the racemic alcohols or meso-diols.

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Isolation, Structure Elucidation, Biosynthesis, and Synthesis of Antalid, a Secondary Metabolite from Polyangium species

The isolation, structure elucidation, and synthesis of antalid (1), a novel secondary metabolite from Polyangium sp., is described herein. The structure elucidation of 1 was performed with the aid of mass spectrometry, high field NMR experiments, and crystal structure analysis. The absolute configuration of antalid was confirmed through the Mosher ester method and ultimately by total synthesis. In addition, the biosynthetic origin of this hybrid PKS-NRPS natural product was unraveled by the in silico analysis of its biosynthetic gene cluster.

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Quinuclidine – Wikipedia,
Quinuclidine | C7H757N | ChemSpider