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Stereoselective synthesis of maresin 1

Maresin 1 is a potent anti-inflammatory and pro-resolving lipid mediator derived from docosahexaenoic acid. The total synthesis of maresin 1 is achieved in 10 steps and in 7% overall yield. The Evans-Nagao aldol reaction between (2E,4E)-5-bromopenta-2,4-dienal and different chiral auxiliaries is investigated. The reported synthesis is efficient and highly stereoselective, affording multi-milligram quantities of this biologically interesting lipid mediator.

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New C4-chiral 1,3-Thiazolidine-2-thiones: Excellent Chiral Auxiliaries for Highly Diastereocontrolled Aldol-Type Reactions of Acetic Acid and alpha,beta-Unsaturated Aldehydes

Diastereocontrolled aldol-type reactions between tin(II) enolates of 3-acetyl-4(S)-ETT (6a) and 3-acetyl-4(S)-IPTT (6b) and alpha,beta-unsaturated aldehydes 7a-c were successfully carried out to give, with highly diastereoselectivity, compounds 9a-e (major products) and 10a-e (minor products).The reaction conditions were also investigated in detail.

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Synthetic studies towards lagunamide C: Polyketide assembly investigations

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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Diastereoselective and Catalytic alpha-Alkylation of Chiral N-Acyl Thiazolidinethiones with Stable Carbocationic Salts

Direct nickel-catalyzed alkylation of chiral N-acyl-4-isopropyl-1,3-thiazolidine-2-thiones using a commercially available nickel(II) complex, (Me3P)2NiCl2, has been developed for tropylium and trityl tetrafluoroborate salts. The reaction provides a single diastereomer of the corresponding adducts in good to high yields, which, in turn, can be easily converted into a wide array of enantiomerically pure compounds that are difficult to obtain by other asymmetric procedures.

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Total synthesis of the lipid mediator PD1n-3 DPA: Configurational assignments and anti-inflammatory and pro-resolving actions

The polyunsaturated lipid mediator PD1n-3 DPA (5) was recently isolated from self-resolving inflammatory exudates of 5 and human macrophages. Herein, the first total synthesis of PD1n-3 DPA (5) is reported in 10 steps and 9% overall yield. These efforts, together with NMR data of its methyl ester 6, confirmed the structure of 5 to be (7Z,10R,11E,13E,15Z,17S,19Z)-10,17- dihydroxydocosa-7,11,13,15,19-pentaenoic acid. The proposed biosynthetic pathway, with the involvement of an epoxide intermediate, was supported by results from trapping experiments. In addition, LC-MS/MS data of the free acid 5, obtained from hydrolysis of the synthetic methyl ester 6, matched data for the endogenously produced biological material. The natural product PD1 n-3 DPA (5) demonstrated potent anti-inflammatory properties together with pro-resolving actions stimulating human macrophage phagocytosis and efferocytosis. These results contribute new knowledge on the n-3 DPA structure-function of the growing numbers of specialized pro-resolving lipid mediators and pathways.

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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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Synthesis of dysideaproline e using organocatalysis

(S)-4,4-Dichloro-3-methylbutanoic acid was prepared in 51% overall yield from commercially available starting materials using an organocatalytic transfer hydrogenation to 4,4-dichloro-3-methylbut-2-enal in the key step. The (S)-dichloro acid was used as an intermediate in the first total synthesis of dysideaproline E and a diastereomer confirming the structure of the natural product.

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Stereoselective Alkylation of (S)-N-Acyl-4-isopropyl-1,3-thiazolidine-2-thiones Catalyzed by (Me3P)2NiCl2

The structurally simple (Me3P)2NiCl2 complex catalyzes SN1-type alkylations of chiral N-acyl thiazolidinethiones with diarylmethyl methyl ethers and other stable carbenium cations. The former can contain a variety of functional groups and heteroatoms at the alpha-position. The resultant adducts are isolated as single diastereomers in high yields and can be converted into enantiomerically pure derivatives in a straightforward manner.

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Highly Enantioselective Claisen-Type Acylation and Dieckmann Annulation

Enantioselective Claisen condensation reactions between various esters 1a-f and 3-acyl-4(S)-IPTT 2a,b employing lithium isopropylcyclohexylamide and HMPA gave acylated products 3a-j in 29-77percent yield and in 22-97percent ee.Asymmetric Dieckmann-type annulation of 4a with KH in DMF followed by methanolysis afforded bicyclic beta-keto methyl ester 6a in 69percent overall yield and in 96percent ee.

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Methods for the synthesis of carbon-13 labelled acids and esters

Syntheses of isotopically labelled putative biosynthetic intermediates to the natural products monocerin 1, hectochlorin 2 and strobilurin A 3 are described. For the preparation of [9,10-13C2] dihydroisocoumarin 10, a stereoselective aldol condensation of 13C2-acetylated chiral auxiliary 5 was used to assemble the labelled C9-C14 fragment. The preferred approaches to the syntheses of [1,2-13C2]5,5-dichlorohexanoic acid 15 and the N-acetylcysteamine derivative of [1,2-13C2]cinnamic acid 19 involved a Horner-Wadsworth-Emmons chain extension and Knoevenagel reaction, respectively. Copyright

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