Synthesis of an Acyloxymethyl Prodrug of the Inositol Phosphate α-Trinositol

ABSTRACT

Acyloxymethylation of an acylated silver salt of α-trinositol gives, after deprotection, membrane permeable 1D-myo-inositol 1,2,6-tris(ethoxycarbonyloxymethyl sodium phosphate). The acyl groups, 3-(4,5-methylenedioxy-2-nitrophenyl)propanoyl, are cleaved by hydrogenolysis.     

Synthesis of Sucrose 4′-(L-Arabinose-2-YL Phosphate) (Agrocinopihe A) Using an Arabinose 2-H-Phosphonate Intermediate

Abstract

The first completed chemical synthesis of Agrocinopine A (5) is presented. The key step in the synthesis was the pivaloyl chloride promoted condensation of a blocked arabinose 2-H-phosphonate derivative 3 with a protected sucrose derivative 1 having a free hydroxyl at 4′-OH. The resulting H-phosphonic acid diester was oxidised in situ with iodine to produce the corresponding phosphodiester 4, which was subsequently deblocked to give Agrocinopine A.     

An improved palladium(II)-catalyzed method for the synthesis of aryl ketones from aryl carboxylic acids and organonitriles

A palladium(II)-catalyzed decarboxylative protocol for the synthesis of aryl ketones has been developed. The addition of TFA was shown to improve the reaction yield and employing THF as solvent enabled the use of solid nitriles and in only a small excess. Using this method, five different benzoic acids reacted with a wide range of nitriles to produce 29 diverse (hetero)aryl ketone derivatives in up to 94% yield.     

N-Aryl Isoleucine Derivatives as Angiotensin?II AT2 Receptor Ligands

A novel series of ligands for the recombinant human AT₂ receptor has been synthesized utilizing a fast and efficient palladium-catalyzed procedure for aminocarbonylation as the key reaction. Molybdenum hexacarbonyl [Mo(CO)₆] was employed as the carbon monoxide source, and controlled microwave heating was applied. The prepared N-aryl isoleucine derivatives, encompassing a variety of amide groups attached to the aromatic system, exhibit binding affinities at best with K_i values in the low micromolar range versus the recombinant human AT₂ receptor. Some of the new nonpeptidic isoleucine derivatives may serve as starting points for further structural optimization. The presented data emphasize the importance of using human receptors in drug discovery programs.     

Effects of feedback from collimating, focusing, and spot-array generating outcoupler gratings in surface-emitting semiconductor lasers

We experimentally demonstrate that a grating outcoupler used for complex beam shaping (spot-array generation) can produce unintentional optical feedback that severely disturbs the integrated in-plane laser that illuminates the coupler. Simulations show that these outcouplers, in contrast to conventional collimating or focusing outcouplers, tend to produce high levels of feedback in spite of the detuning used to suppress feedback. Further, this feedback is focused to high intensity in the laser gain medium. This focused light acts as a seed for the nonlinear self-focusing that causes wave-front distortion and filamentation, which degrades the beam quality.     

Thiol–ene coupling reaction of fatty acid monomers

The reactivities and reaction rates of the thiol–ene coupling reaction of 2‐ethyl‐(hydroxymethyl)‐1,3‐propanediol trimercapto acetate and 2‐ethyl‐(hydroxymethyl)‐1,3‐propanediol trimercapto propionate with two common unsaturated fatty acid methyl esters (methyl oleate and methyl linoleate) were evaluated. The reactions were monitored with real‐time IR and ¹H NMR, which both showed that the mercapto acetate was more reactive than the mercapto propionate. Both thiols were more prone to add to the monounsaturated methyl oleate than to methyl linoleate, which contained two unconjugated double bonds. According to bond energy calculations, the thiol hydrogen of mercapto acetate was somewhat more difficult to abstract than the hydrogen of mercapto propionate. Consequently, the formed S? C bond in the acetate case was stronger than in the propionate case, and so the equilibrium was more shifted toward the addition products. The real‐time IR measurements also showed that the cis unsaturation in methyl oleate isomerized much more quickly than that in methyl linoleate, and this also had an impact on the overall addition rate of the thiols because a trans unsaturation was more reactive than a cis unsaturation. The higher isomerization rates in the oleate systems, compared with those of the linoleate systems, was suggested to be due to a more restricted rotation along the C? C bond of the reacted unsaturation in linoleate. This study showed the importance of trans unsaturations in obtaining reasonable reaction rates in thiol–ene reactions with fatty acid derivatives. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 6346–6352, 2004