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SYNTHESIS OF INSECT ATTRACTANTS (SEX ATTRACTANTS). VIII. STEREOSELECTIVE SYNTHESIS OF FOUR ISOMERS OF 5,7-DODECADIEN-1-OL AND THEIR ACETATES AND ALDEHYDES, COMPONENTS OF THE SEX PHEROMONES OF INSECTS OF THE Lasiocampidae (Lepidoptera) FAMILY

A new method is proposed for the stereoselective synthesis of four stereoisomers of 5,7-dodecadien-1-ol and their acetates and aldehydes on the basis of the Wittig reaction. 7-(2-Tetrahydropyranyloxy)-2-heptyn-1-ol was obtained by the alkylation of 2-propyn-1-ol with 2-(4-bromobutoxy)tetrahydropyran.By hydrogenation in the presence of colloidal nickel catalyst or by reduction with lithium aluminum hydride it was converted into the Z and E isomers respectively of 7-(2-tetrahydropyranyloxy)-2-hepten-1-ol.Oxidation of the alcohol group in the above-mentioned hydroxy acetals led to the corres ponding aldehydes, which then entered into the Wittig reaction with pentylidenetriphenylphosphorane under the conditions for the formation of a double bond with a specific configuration of the isomers (Z and E).Subsequent removal of the tetrahydropyranyl protection of the alkyl group in the Wittig reaction products gave 5,7-dodecadien-1-ols, which were converted into the corresponding acetates of the aldehydes by acetylation of oxidation.The products are components of the sex pheromones of insects of the Lasiocampidae family.

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Tetrahydropyran – Wikipedia,
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Reductive Opening of alpha-Methylspiroketals

Syntheses of 5-methyl-1,7-dioxaspiro<5.5>undecane 4 and its three congeners 5, 6, and 7 (alpha-methylspiroketals), and their reductive ring opening using aluminum hydride or silane – Lewis acid system have been investigated.Each spiroketal was synthesized through stereocontrolled acetalization with 42 – 96percent diastereomeric excess (de).The diisobutylaluminum hydride reduction of alpha-methylspiroketals proceeded via the tight oxocarbenium ion pair complex wherein the C-O bond which located at the opposite site against the C(alpha) – methyl bond was cleaved, affording a configuration-retentive product with 50 – 100percent de.The regioselectivity in the silane – Lewis acid reduction of the simplest monomethylspiroketal 4 was controlled by the equilibration of the two possible oxocarbenium ionic intermediates.On the other hand, dimethylspiroketal 5 and siloxyspiroketal 6 showed moderate to high regio- and stereoselectivity (10-100percent de), that originated from regioselective formation of the oxocarbenium ionic species and the subsequent stereoselective hydride attack.In these cases, the coordination site of the Lewis acid was controlled by the steric interaction of the methyl group on C(alpha) with the Lewis acid.To the resultant oxocarbenium ion, stereoelectronically-favored axial hydride attack occured with high stereoselection.The reduction of benzyloxyspiroketal 7 also exhibited good selectivity (62 – 100percent de) while the outcome was opposite to those of 5 and 6.Such a dramatic change could be attributed to the bidentate chelation of the Lewis acid to both the benzyl ether and the neighboring acetal oxygens.The whole procedure, the thermodynamic spiroketalization and the subsequent reductive ring opening, could be regarded as a remote stereochemical control using the spiroketal templates.

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Tetrahydropyran – Wikipedia,
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SYNTHESIS OF 10-METHYL-14,16-(5,3-ISOXAZOLO)PROSTANOIDS

A series of 10-methyl-substituted analogs of prostaglandin A2, containing an isoxazole ring in the omega-chain, were synthesized usind regio- and stereospecific alkylation of the enol ether of 2-methylcyclopentane-1,3-dione and the nitrile oxide method.

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Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics

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Milbemycin Synthesis: Asymmetric Synthesis of Spiroketals from Methyl alpha-D-Glucopyranoside

The 6-chloro-4,6-dideoxygalactoside 8 was prepared by selective dichlorination of methyl alpha-D-glucopyranoside 6 followed by hydrogenolysis, and was converted into the epoxyalkyldithioacetal 10 by treatment with propane-1,3-dithiol, protection, and formation of the epoxide.With nucleophiles, the epoxyalkyldithioacetal underwent opening of the epoxide, whereas with strongly basic reagents abstraction of the dithiane proton at C-2 followed by elimination gave the epoxy hydroxy ketone dithioacetal 34.This chemistry was used to prepare a series of anti-1,3-diols 36, 38 and 40 and should be useful for natural-product synthesis.Using the vinyllithium reagent derived from iodide 57, the diol 60 corresponding to the C(11)-C(21) fragment of milbemycin E 1 was prepared, and this was taken through to the spiroketal 64 as a model for a proposed synthesis of the C(11)-C(25) fragment of a milbemycin.The anti-diols 36 and 40 were taken through to the spiroketals 74 and 69, respectively, so providing an asymmetric synthesis of fully functionalised milbemycin spiroketals.

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Tetrahydropyran – Wikipedia,
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Facile synthesis of the fused 6-6-5 ring system containing chroman ring from 2-(1-hydroxy-5-alkenyl)phenol derivatives via intramolecular inverse- electron-demand diels-alder reaction

A simple and facile synthesis of the fused 6-6-5 ring system, i.e., 1,2,3,3a,4,9b-hexahydrocyclopenta[c][1]benzopyrans, was achieved through the intramolecular [4+2] cycloaddition of o-quinonemethides generated from 2-(1- hydroxy-5-alkenyl)phenol derivatives under acidic conditions. In general, cis-fused tricyclic compounds of 6-6-5 ring system were obtained as the major products. Reactivity and selectivity of the cycloaddition reaction depended on the substituents on the aromatic ring and in the dienophilic olefin moiety.

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Tetrahydropyran – Wikipedia,
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Synthesis of (6E,11Z)-6,11-Hexadecadien-1-yl Acetate

1-Bromo-non-4(Z)-ene (II) on reaction with the dianion of propargyl alcohol in liq.NH3 yields the acetylenic alcohol (III) which on LAH reduction gives (2E,7Z)-2,7-dodecadien-1-ol (IV).The bromide (V) obtained from IV when coupled with 1-bromo-4-tetrahydropyranyloxybutane in the presence of Li2CuCl4 affords VI which on hydrolysis gives VII.Acetylation of VII (Py/Ac2O) leads to the title compound (I).

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Asymmetric Bioreduction of Ethyl 3-Oxobutanoate by Immobilized Baker’s Yeast Entrapped in Calcium Alginate Beads. Application of the Immobilized Biocatalyst to the Synthesis of (5Z,13S)-5-Tetradecen-13-olide, Aggregation Pheromone of Cryptolestes Grain Beetle

Immobilized baker’s yeast entrapped in calcium alginate beads of 1-1.5 mm diameter was reusable more than 10 times and stereoselectively reduced ethyl 3-oxobutanoate to the corresponding (S)-hydroxy ester in high chemical and optical yields.The immobilized biocatalyst was also successfully used for an asymmetric synthesis of (5Z,13S)-5-tetradecen-13-olide, a synergist of the aggregation pheromone of the flat grain beetle.

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Tetrahydropyran – Wikipedia,
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Racemic prostaglandins of the 2-series and analogs thereof

This invention is racemic PGE2, racemic PGF2alpha, racemic PGF2 beta, racemic PGA2, racemic PGB2, analogs of those, and processes for making them. These compounds are useful for a variety of pharmacological purposes, including anti-ulcer, inhibition of platelet aggregation, increase of nasal patency, abortion, and wound healing.

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Synthesis, SARs, and pharmacological characterization of 2-Amino-3 or 6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid derivatives as potent, selective, and orally active group II metabotropic glutamate receptor agonists

(+)-2-Aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (4, LY354740), a highly selective and orally active group II metabotropic glutamate receptor (mGluR) agonist, has increased interest in the study of group II mGluRs. Our interest focused on a conformationally constrained form of compound 4, because it appeared that the rigid form resulted in not only selectivity for group II mGlur but was orally active. Therefore, we introduced a fluorine atom to compound 4, based on the molecular size (close resemblance to hydrogen atom) and electronegativity (effects on the electron distribution in the molecule) of this atom and carbon-fluorine bond energy. Compound (+)-7 (MGS0008), the best compound among 3-fluoro derivatives 7-10, retained the agonist activity of compound 4 for mGluR2 and mGluR3 ((+)-7: Ec50 = 29.4 ¡À 3.3 nM and 45.4 ¡À 8.4 nM for mGluR2 and mGluR3, respectively; 4: EC50 = 18.3 ¡À 1.6 nM and 62.8 ¡À 12 nM for mGluR2 and mGluR3, respectively) and increased the oral activity of compound 4 ((+)-7: ED50 = 5.1 mg/kg and 0.26 mg/kg for phencyclidine (PCP)-induced hyperactivy and PCP-induced head-weaving behavior, respectively; 4: ED50 = > 100 mg/kg and 3.0 mg/kg for PCP-induced hyperactivity and PCP-induced head-weaving behavior, respectively). In addition, a compound [3H]-(+)-7 binding study using mGluR2 or 3 expressed in CHO cells was successful ((+)-7: K(i) = 47.7 ¡À 17 nM and 65.9 ¡À 7.1 nM for mGluR2 and mGluR3, respectively; 4: K(i) = 23.4 ¡À 7.1 nM and 53.5 ¡À 13 nM for mGluR2 and mGluR3, respectively). On the basis of a successful result of compound 7, we focused on the introduction of a fluorine atom on the C6 position of compound 4. (1R,2S,5R,6R)-2-Amino-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid ((-)-11) exhibited a high degree of agonist activity for group II mGluRs equal to that of compound 4 or 7 ((-)-11: K(i) = 16.6 ¡À 5.6 and 80.9 ¡À 31 nM for mGluR2 and mGluR3, respectively). Our interest shifted to modification on CH2 at C4 position of compound 11, since replacement of the CH2 group with either an oxygen atom or sulfur atom yielded compound 5 or 6, resulting in increased agonist activity. We selected a carbonyl group instead of CH2 at the C4 position of compound 11. The carbonyl group might slightly change the relative conformation of three functional groups, the amino group and two carboxylic acids, which have important roles in mediating the interaction between group II mGluRs and their ligand, compared with the CH2 group of 4, oxygen atom of 5, and sulfur atom of 6. (1R,2S,5S,6S)-2-Amino-6-fluoro-4-oxobicyclo[3.1.0]hexane-2,6-dicarboxylic acid monohydrate ((+)-14, MGS0028) exhibited a remarkably high degree of agonist activity for mGluR2 (K(i) = 0.570 ¡À 0.10 nM) and mGluR3 (K(i) = 2.07 ¡À 0.40 nM) expressed in CHO cells but not mGluR4, 6, 7, 1a, or 5 expressed in CHO cells (K(i) = > 100 000 nM). Furthermore, compound (+)-14 strongly inhibited phencyclidine (PCP)-induced head-weaving behavior (ED50 = 0.090 mug/kg) and hyperactivity (ED50 = 0.30 mg/kg) in rats. Thus, (+)-7 and (+)-14 are potent, selective, and orally active group II mGluR agonists and might be useful not only for exploring the functions of mGluRs but in the treatment of schizophrenia.

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Tetrahydropyran – Wikipedia,
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Racemic prostaglandins of the 2-series and analogs thereof

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Tetrahydropyran – Wikipedia,
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