Acyclic Portion Research Articles

Difficulties to Determine the Absolute Configuration of Guaiaretic Acid

An account of the difficulties to determine the absolute configuration (AC) of guaiaretic acid (1a), using contemporary methodology, is described in commemoration of the century of its structure elucidation. In fact, the herein studied molecule was the derived diacetate 1b, since the natural lignan slowly decomposes upon manipulation. Single crystal X-ray diffraction of 1b demonstrated the structure, but calculation of Flack and Hooft parameters to know the AC was unsuccessful since the crystals were triclinic, P-1, which is a centro-symmetric space group. In turn, manual band to band comparison of experimental and DFT B3LYP/DGDZVP calculated VCD spectra of 1b allowed ascertaining its AC, although automatic comparison using the Compare VOA software was not very successful. This behavior is associated to the fact that the studied molecule has a sole stereogenic center located on the acyclic portion of a carbon chain possessing two quite similar substituents. The behavior is discussed in relation to cases where the molecular flexibility also generates a very large number of conformers.

N-Heterocyclic Carbene-Copper-Catalyzed Group-, Site-, and Enantioselective Allylic Substitution with a Readily Accessible Propargyl(pinacolato)boron Reagent: Utility in Stereoselective Synthesis and Mechanistic Attributes.

The first instances of catalytic allylic substitution reactions involving a propargylic nucleophilic component are presented; reactions are facilitated by 5.0 mol % of a catalyst derived from a chiral N-heterocyclic carbene (NHC) and a copper chloride salt. A silyl-containing propargylic organoboron compound, easily prepared in multigram quantities, serves as the reagent. Aryl- and heteroaryl-substituted disubstituted alkenes within allylic phosphates and those with an alkyl or a silyl group can be used. Functional groups typically sensitive to hard nucleophilic reagents are tolerated, particularly in the additions to disubstituted alkenes. Reactions may be performed on the corresponding trisubstituted alkenes, affording quaternary carbon stereogenic centers. Incorporation of the propargylic group is generally favored (vs allenyl addition; 89:11 to >98:2 selectivity); 1,5-enynes can be isolated in 75-90% yield, 87:13 to >98:2 SN2'/SN2 (branched/linear) selectivity and 83:17-99:1 enantiomeric ratio. Utility is showcased by conversion of the alkynyl group to other useful functional units (e.g., homoallenyl and Z-homoalkenyl iodide), direct access to which by other enantioselective protocols would otherwise entail longer routes. Application to stereoselective synthesis of the acyclic portion of antifungal agent plakinic acid A, containing two remotely positioned stereogenic centers, by sequential use of two different NHC-Cu-catalyzed enantioselective allylic substitution (EAS) reactions further highlights utility. Mechanistic investigations (density functional theory calculations and deuterium labeling) point to a bridging function for an alkali metal cation connecting the sulfonate anion and a substrate's phosphate group to form the branched propargyl addition products as the dominant isomers via Cu(III) π-allyl intermediate complexes.

ChemInform Abstract: Isolation, Structural Elucidation, and Absolute Stereochemistry of Enigmazole A, a Cytotoxic Phosphomacrolide from the Papua New Guinea Marine Sponge Cinachyrella enigmatica.

Enigmazole A (1), a novel phosphate-containing macrolide, was isolated from a Papua New Guinea collection of the marine sponge Cinachyrella enigmatica. The structure of 1, including the absolute stereochemistry at all eight chiral centers, was determined by a combination of spectroscopic analyses and a series of microscale chemical derivatization studies. Compound 1 is comprised of an 18-membered phosphomacrolide that contains an embedded exomethylene-substituted tetrahydropyran ring and an acyclic portion that spans an embedded oxazole moiety. Two additional analogues, 15-O-methylenigmazole A and 13-hydroxy-15-O-methylenigmazole A, were also isolated and assigned. The enigmazoles are the first phosphomacrolides from a marine source and 1 exhibited significant cytotoxicity in the NCI 60-cell line antitumor screen, with a mean GI(50) of 1.7 microM.

Isolation, structural elucidation, and absolute stereochemistry of enigmazole A, a cytotoxic phosphomacrolide from the Papua New Guinea marine sponge Cinachyrella enigmatica.

Enigmazole A (1), a novel phosphate-containing macrolide, was isolated from a Papua New Guinea collection of the marine sponge Cinachyrella enigmatica. The structure of 1, including the absolute stereochemistry at all eight chiral centers, was determined by a combination of spectroscopic analyses and a series of microscale chemical derivatization studies. Compound 1 is comprised of an 18-membered phosphomacrolide that contains an embedded exomethylene-substituted tetrahydropyran ring and an acyclic portion that spans an embedded oxazole moiety. Two additional analogues, 15-O-methylenigmazole A and 13-hydroxy-15-O-methylenigmazole A, were also isolated and assigned. The enigmazoles are the first phosphomacrolides from a marine source and 1 exhibited significant cytotoxicity in the NCI 60-cell line antitumor screen, with a mean GI(50) of 1.7 microM.

ChemInform Abstract: Remarkably Chemoselective Indium‐Mediated Coupling en Route to the C21—C40 Acyclic Portion of the Azaspiracids.

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Remarkably chemoselective indium-mediated coupling en route to the C21–C40 acyclic portion of the azaspiracids

A densely functionalized acyclic intermediate representing the C21–C40 portion of the novel marine natural product azaspiracid was prepared via a chemoselective indium-mediated coupling between C21–C27 and C28–C40 intermediates. Although the coupling partners contained aldehyde, azide, ketone, enone, and lactone functionalities, the C21–C27 allylic species added selectively to the aldehyde of a C28–C40 intermediate under aqueous indium-mediated conditions. The C21–C27 and C35–C40 fragments were prepared in a divergent fashion from a common syn-1,3-dimethyl synthon 9 .

Fast-atom Bombardment Mass Spectrometry of Some Nucleoside Analogs

A new series of thymine derivative acyclic nucleosides, with mono- or polyfluorosubstitution on the acyclic portion of the molecules have been studied by fast-atom bombardment mass spectrometry, with the aid of metastable ion studies and deuterium labelling experiments. The protonated molecules show four main metastable-supported fragmentation processes, consisting of loss of CX

Degradation of neurohypophyseal hormones by brain extracts and purified brain enzymes.

Rat brain tissue inactivates oxytocin and arginine-vasopressin by the release of the C-terminal dipeptide and glycinamide. Most of the enzymic activities are present in the 100,000g supernatant fraction although some activity is bound to particulates. Extracts prepared in isotonic sucrose exhibit a higher ratio of dipeptide to glycinamide released than do comparable preparations in hypotonic medium. Inactivation of oxytocin is also demonstrated in homogenates of the median eminence region. Purified arylamidase from pig brain inactivates neurohypophyseal hormones negligibly and pig brain aminopeptidase inactivates not at all. It is suggested that enzymes present in brain inactivate neurohypophyseal hormones primarily by hydrolysis of peptide bonds in the acyclic portion, and to a minor degree by initial cleavage of the N-terminal half-cystine residue.