Lower Side Chain Research Articles

The effect of side-chain branch position on the thermal properties of poly(3-alkylthiophenes)

Branching closer to the backbone causes tighter packing in the side-chain direction and lower side chain and backbone dynamics.

Novel branched polymers and their structural effects on intercalation into Na-MMT and silica fume suspensions

Various branched polymers with different functionalities and side chains were synthesized as dispersant and their molecular structures were characterized by Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance, and thermogravimetric analysis (TGA) methods. It was found that the amount of side chain and kind of acidic or ionic functions had influences on the properties of the dispersants. The effect of side chain density of the dispersants on the intercalation of sodium montmorillonite (Na-MMT) was also investigated. The results of X-ray diffraction, and FTIR and TGA analyses showed that the branched polymers with a higher amount of side chains and acidic functions were suitable to provide efficient intercalation and adsorption. In addition, a weak intercalation of dispersant with a lower side chain density and neutral functions into the Na-MMT interlayer was observed. The role of side chain density and acidic/neutralize functionalities of dispersants on both the yield stress and viscosity of reactive silica fume suspensions was investigated. It was found that the dispersant with acidic functionalities and low amount of side chains increased the yield stress and viscosity. A lower viscosity was also recorded for the suspensions in the presence of Na-MMT. Moreover, the suspension prepared by the dispersant with a high side chain density exhibited higher fluidity and lower viscosity.

A Ring‐Closing Metathesis (RCM)‐Based Approach to Mycolactones A/B

The total synthesis of the mycobacterial toxins mycolactones A/B (1 a/b) has been accomplished based on a strategy built around the construction of the mycolactone core through ring-closing metathesis. By employing the Grubbs second-generation catalyst, the 12-membered core macrocycle of mycolactones, with a functionalized C2 handle attached to C11, was obtained in 60-80 % yield. The C-linked upper side chain (comprising C12-C20) was completed by a highly efficient modified Suzuki coupling between C13 and C14, while the attachment of the C5-O-linked polyunsaturated acyl side chain was achieved by Yamaguchi esterification. Surprisingly, a diene containing a simple isopropyl group attached to C11 could not be induced to undergo ring-closing metathesis. By employing fluorescence microscopy and flow cytometry techniques, the synthetic mycolactones A/B (1 a/b) were demonstrated to display similar apoptosis-inducing and cytopathic effects as mycolactones A/B extracted from Mycobacterium ulcerans. In contrast, a simplified analogue with truncated upper and lower side chains was found to be inactive.

ChemInform Abstract: Towards a Large Scale Preparation of Mexiprostil.

Abstract The enantioselective synthesis of mexiprostil (16R-16-methoxy-16-methyl PGE1 methyl ester) is described. The assembly of the prostaglandin framework has been accomplished by the three component coupling process, via consecutive linking of the ω and α-sidechain to unsubstituted (R)-4-hydroxy-2-cyclopentenone, and alternatively by a conjugate addition of the ω-side chain to a (R)-4-hydroxy-2-cyclopentenone in which the α-side chain is already incorporated. The required lower side chain building block is prepared enantioselectively from nerol utilising the Sharpless epoxidation reaction.

Synthesis of tetrahydrodicranenone B

The naturally occurring cyclopentenone, tetrahydrodicranenone B (1J), has been synthesized from the cyclopentenone (3), prepared by Birch reduction/alkylation of 6-methoxyindanone followed by ozonolysis of the dihydroindanone (2). The lower side chain was elongated by selective addition of a five-carbon Grignard reagent to the aldehyde (6), obtained from the ester (3), to give the alcohol (7). The alcohol (7) could also be prepared from the 7-methoxyindanone (14), in which all the carbons of the lower side chain are already present, by a similar reductive alkylation/ozonolysis sequence (Scheme 3). The alcohol (7) was converted into the natural product by radical deoxygenation, followed by functional group manipulation.

Synthesis and gastric antisecretory properties of allenic 16-phenoxy-omega-tetranor prostaglandin E analogs

In order to improve the modest oral activity of PGE 2 as an inhibitor of gastric acid secretion, analogs were prepared and tested orally in histamine-challenged rats. Insertion of a double bond at C-4, resulting in the 4,5-allene analog of PGE 1, gave a small increase in activity. Introduction of the ω-tetranor-16-phenoxy lower sidechain, a modification know to enhance activity in the PGF series, gave an eight-fold increase in activity. The analog having both modifications (enprostil, 2 ) showed a six hundred-fold increase in oral antisecretory activity over PGE 2, which may reflect a potentiation effect. Modification of enprostil at C-1 (various esters) and at C-11 (11-methyl, 11-deoxy) generally resulted in compounds of high activity while modifications at other sites generally resulted in significant reductions in activity.

Synthesis of tetrahydrodicranenone B

The naturally occurring cyclopentenone, tetrahydrodicranenone B (1), has been synthesised from 6-methoxyindanone by a route which involves reductive alkylation and ozonolysis to the key cyclopentenone (3), followed by elongation of the lower side chain to give the alcohol (7), and functional group manipulation.

Synthesis of [17,18- 3H] trans-13-azaprostanoic acid. A labeled probe for the PGH 2/TXA 2 receptor

Because of its highly unstable nature, TXA 2, produced by platelet metabolism of arachidonic acid, does not lend itself to use as a receptor probe for its own receptor. As such, the stable TXA 2/PGH 2 antagonist, trans-13-azaprostanoic acid ( trans-13-APA, 12b), was prepared as the [17,18 3H] derivative ([ 3H] trans-13-APA, 12c) to study this receptor and to better evaluate the mechanism of action of these azaprostanoids. Tritiated trans-13-APA, 12c, was prepared in nearly theoretical specific activity (57 Ci/mmole) from (17z)- trans-13-azaprost-17-enoic acid (11b) by catalytic tritiation. The unsaturated 11b was prepared by condensation of cis-7-amino-3-heptene (8) with 2-(6-carboxyhexyl) cyclopentanone (9), NaBH 4 reduction, chromatography, and hydrolysis of the trans isomer so isolated. The olefins 11a and b were also of biochemical interest because of the unsaturation in the lower side chain. The presence of similar unsaturation in PGH 3 (4) and TXA 3 (3) renders these prostaglandins inactive as proaggregatory agents. Evaluation of the antiaggregatory activity of 11a and b indicated it to be about the same potency in inhibiting human platelet aggregation as the parent cis and trans-13-APAs, suggesting that introduction of a double bond at the 17 position in platelet prostaglandin antagonists is unlikely to result in enhanced antiplatelet activity.