Hydroxy Moiety Research Articles

Pumiliotoxin alkaloids: relationship of cardiotonic activity to sodium channel activity and phosphatidylinositol turnover

The cardiotonic activity of pumiliotoxin B (PTX-B, 6-(6',7'-dihydroxy-2',5'-dimethyl-(E)-4'-octenylidene)-8-hydroxy-8 -methyl-1- azabicyclo[4.3.0]nonane) as assessed in guinea pig atrial preparations is markedly dependent on the nature of the 6-alkylidene side chain. Pumiliotoxin A (PTX-A), which differs from PTX-B only in lacking the 7'-hydroxy moiety, is much less active than PTX-B. Alteration in the configuration of the 6'- and/or 7'-hydroxy side chain moieties in synthetic isomers of PTX-B reduces activity, while the lack of such moieties or replacement with methoxy or ketone moieties in PTX-B or PTX-A analogues yields cardiodepressant compounds. PTX-B markedly stimulates phosphoinositide turnover in atrial and brain preparations and sodium influx in brain preparations, while analogues that are cardiac depressant or have low cardiotonic activity have no or minimal effects on such parameters. It is suggested that activation of sodium channels and resultant stimulation of phosphoinositide breakdown play a role in the cardiotonic activity of pumiliotoxin alkaloids.

A Protection-Deprotection Method for the Synthesis of Substituted Benzoyloxybenzoates

Abstract Common syntheses of phenyl benzoyloxybenzoates generally produce products in low yields. A variety of synthetic pathways were employed in an attempt to increase the overall yield of the final product. It was found that catalytic agents such as boron trifluoride-etherate (BF3 Et2O), 1,3-dicyclohexylcarbodiimide (DCC), and 4-N, N-di-methylaminopyridine (DMAP) were relatively ineffective in these processes. However. protection of the hydroxy moiety of an appropriately substituted benzoic acid with methyl chloroformate, followed by esterification under normal conditions, and deprotection with ammonia in ethanol produces the hydroxy-benzoyloxybenzoate intermediate. This material can be used in further esterifications to produce phenyl benzoyloxybenzoate compounds in good yield. Materials such as the triply reentrant compound 4-n-nonyloxyphenyl 4-nitrobenzoyloxybenzoate (DB9ONO2) can be prepared by this method.

Synthesis of Polyisoprenepolyols Having Multiple Tertiary Hydroxy MoietiesViaHydromagnesation

Abstract Synthesis of polyisoprenepolyols possessing multiple tertiary hydroxy moieties has been achieved efficiently by using hydromagnesation.

Pumiliotoxins: magnetic resonance spectral assignments and structural definition of pumiliotoxins A and B and related allopumiliotoxins

Magnetic resonance spectral assignments for carbon-13 and protons of pumiliotoxin A, B and 251D and of related allopumiliotoxins (7-hydroxy congeners) are presented. Pumiliotoxin A and its 7-hydroxy congener allopumiliotoxin 323B can occur as pairs of 15-hydroxy epimers in dendrobatid frogs. Allopumiliotoxin 323B' and 323B'' and allopumiliotoxin 267A (the 7-hydroxy congener of 251D ) have 7-axial hydroxy moieties. Allopumiliotoxin 339A and 339B are, respectively, the 7- axial-hydroxy and 7-equatorial-hydroxy congeners of pumiliotoxin B. Formation of ring phenyl boronides occurs only with allopumiliotoxin 339B which has the 7-equatorial hydroxy cis to the 8-axial hydroxy of the indolizidine ring.

Determination of steroid profiles in healthy and diseased states: identification and quantitation of a block of 17α-hydroxylase

The steroid metabolic profile on a patient with a suspected block in steroid biosynthesis was analyzed by gas chromatography and gas chromatography-mass spectrometry. The results of this work led to an interpretation of a block at the 17α-hydroxylase step. Although the steroid metabolic profile was complex, we could not detect any steroids with a hydroxy moiety at position C-17. The use of gas chromatography-mass spectrometry, in this case, was the method of choice for a final diagnosis because of the confusion that resulted from other, more classical, forms of analysis. Data from our patient's sample are reported and compared to normals and to other cases where a block in 17α-hydroxylase have been reported.

Evidence for genetically independent allosteric regulatory domains of the protein M1 subunit of mouse ribonucleotide reductase.

Ribonucleotide reductase is responsible for the reduction of the 2'-hydroxy moiety of all four ribonucleoside diphosphates to the corresponding deoxyribonucleotides. The overall activity of the enzyme is regulated by the allosteric effectors ATP (activator) and dATP (inhibitor), and the enzyme's substrate specificity is also controlled by nucleotide effectors. For instance, wild type ribonucleotide reductase from mouse T-lymphoma (S49) cells requires dGTP as a positive effector for ADP reduction. This effect of dGTP causes a reciprocal inhibition of CDP reduction. The dGuo-L mutant cell line, resistant to growth inhibition by exogenous deoxyguanosine, contains a nucleotide-binding subunit, protein M1, that conveys to its CDP reductase an insensitivity to dGTP (and dTTP) inhibition. The dGuo-L protein M1 also shows a decreased capacity to use ADP as a substrate, and therefore, the regulation of the substrate specificity is altered in the mutant protein M1. Another mutant cell line, dGuo-200-1, is resistant to deoxyadenosine and its ribonucleotide reductase is abnormally resistant to inhibition by dATP. The isolated mutant protein M1 from dGuo-200-1 cells has a CDP reductase activity which is stimulated by dATP, unlike the wild type enzyme which is inhibited by dATP. It appears that this mutant enzyme has lost the capacity to distinguish between dATP and ATP, but is still sensitive to regulation by dGTP and dTTP. Thus, the site of protein M1 regulating overall activity is altered in the dGuo-200-1 mutant, while the site regulating substrate specificity is normal. These characteristics of the mutants provide genetic evidence for two independent allosteric domains of protein M1, each responsible for a different aspect of nucleotide sensitivity of ribonucleotide reductase.

Biopolyester Membranes of Plants: Cutin and Suberin

Cutin, a biopolyester composed of hydroxy and epoxy fatty acids, is the barrier between the aerial parts of higher plants and their environment. Suberin a polymer containing aromatics and polyesters, functions as a barrier in underground parts, wound surfaces, and a variety of internal organs. The composition and probable structure of these polymers are discussed. The biosynthesis of the hydroxy, epoxy, and dicarboxylic acids of the polyesters from the common cellular fatty acids is elucidated. An extracellular enzyme transfers the hydroxy and epoxyacyl moieties from their coenzyme A derivatives to the growing polyester. The enzymes acting in the biodegradation of the polyesters have been isolated from fungi, pollen, and mammals and characterized. The function and possible practical implications of these polyester barriers are briefly discussed.

Thin-layer chromatography-mass spectrometry for the identification of sapogenins from Digitalis species.

A method is described for the identification of the sapogenins of several Digitalis species. The steroids are separated by repeated development thin-layer chromatography and identified by means of high resolution mass spectrometry. The spectra of tigogenin, gitogenin, digalogenin and digitogenin are recorded. These spectra are of particular use in establishing the position of extra hydroxy moieties in the steroid nuclei. Several species of Digitalis were screened for their sapogenin content. D. purpurea, D. mertonensis and D. lutea were found to contain tigogenin and digitogenin in small amounts, the principal steroid being gitogenin, whilst D. ambigua and D. lanata contained all four steroids.

Synthesis of poly[4(5)‐vinylimidazole‐co‐γ‐vinyl‐γ‐butyro‐lactone] and its catalytic activity in ester hydrolysis

AbstractCopolymerizations of 4(5)‐vinylimidazole (1) and γ‐vinyl‐γ‐butyrolactone (2) initiated by 2,2′‐azoisobutyronitrile or benzoyl peroxide were carried out. The initiators did not affect the radical reactivity ratio (r). In addition, the reactivity ratio was not influenced by methanol as solvent. The following ratios were obtained r1 = 20,0 ± 0,8 and r2 = 0,030 ± 0,002.The catalytic activity of the copolymers in the hydrolyses of p‐nitrophenyl acetate (4) and 3‐acetoxy‐N,N,N‐trimethylanilinium iodide (5) at pH = 8,0 was found to be more than twice as high as that of a random terpolymer containing imidazole, carboxylic acid, and hydroxy moieties.