Acetyl Side Chain Research Articles

AB Initio Geometries for C 2n+1H, C 2n+1H +, and C 2n+1H 2 Species for N = 1,2,3

Ab initio geometries are reported for C<SUB>2n+1</SUB>H, C<SUB>2n+1</SUB>H<SUP>+</SUP>, and various C<SUB>2n+1</SUB>H<SUB>2</SUB> species (n = 1, 2, 3). Different planar conformations of the C<SUB>2n+1</SUB>H<SUB>2</SUB> molecules are examined, including quasi-linear chains, carbenes based on a three-membered ring with acetylenic side chains, and (H<SUB>2</SUB>C)C<SUB>2n</SUB> species related to vinylidenecarbene. Excited electronic states of linear HC<SUB>7</SUB>H are also considered briefly. For the early members of each series, comparison is made with spectroscopic and astronomical data.

Synthesis of α-amino acids with β,γ-unsaturated side chains

α-Amino acids with allenyl, vinyl, and acetylenic side chains can be synthesized using non-enolate based strategies. The ester enolate-Claisen rearrangement applied to propargylic esters of N -protected α-amino acids ie of limited utility since only poor yields of allenic product are obtained with the N-Boc glycine esters, the system which give the most reproducible results. However, α-allenyl-α-amino acids that are fully functionalized on the α-carbon are available through the agency of 4-allenyl-2-phenyloxazolones 4 (obtained from propargyl esters of N-benzoyl protected amino acids via cyclization and Claisen rearrangement) provided that Meerwein's reagent is used to facilitate hydrolysis of the benzamide function in 5 . A variety, of α-substituted glycinates, including those with α-vinyl and α-acetylenic functions, can be prepared using a two-step sequence involving condensation of the cationic glycine synthon 22 with various organomagnesiu reagents, followed by hydrolysis.

Inhibition of myocardial Ca2+ channels by three dihydropyridines with different structural features: potential‐dependent blockade by Ro 18–3981

Inhibition of myocardial Ca2+ channels was investigated for three dihydropyridines with different structural features: Ro 18-3981, darodipine (PY 108-068) and nifedipine. Ro 18-3981 contains a sulphamoyl acetyl side-chain. In voltage-clamps experiments with isolated cardiac myocytes of guinea-pig, Ro 18-3981 caused a concentration-dependent inhibition of the Ca2+ current, which was influenced by the membrane holding potential. A markedly greater inhibition by Ro 18-3981 was observed when myocytes were depolarized (to +10 mV) from a holding potential (Vh) of -20 mV (IC50 = 2.3 nm) than at -50 mV (IC50 = 100 nM). The three dihydropyridines caused a concentration-dependent reduction in contractile force of isolated, electrically-stimulated left atria of the guinea-pig. Elevation of the extracellular K+ concentration from 5.9 to 24 mM resulted in a significant reduction in negative inotropic IC50 values for Ro 18-3981 (137 fold), darodipine (8 fold) and nifedipine (20 fold). The affinity of these drugs for the high-affinity (+)-[3H]-PN 200-110 binding site was determined in guinea-pig cardiac membranes. The KD value of Ro 18-3981 (1.0 nM) was similar to the IC50 value for blockade of ICa at a Vh of -20 mV (2.3 nM), i.e. at a level of near-maximal depolarization. Thus, structurally-different dihydropyridines exert potential-dependent inhibition of myocardial Ca2+ channel activity consistent with the modulated receptor hypothesis. These results demonstrate that blockade of myocardial excitation-contraction coupling by Ca2+ entry blockers is also potential-dependent.

Synthesis of 3β‐Hydroxy[21‐14C]‐5β‐pregn‐8(14)‐en‐20‐one from Chenodeoxycholic Acid

Abstract3β‐Hydroxy[21‐14C]5β‐pregn‐8(14)‐en‐20‐one (17) was prepared from chenodeoxycholic acid (1a). The synthetic sequence involved: (i) degradation of the bile‐acid side chain to an etianic acid; (ii) formation of the 8(14)‐double bond; (iii) inversion of the configuration at C(3); (iv) construction of the acetyl side chain at C(17) with the required isotopic label at C(21). Structures of all described products were confirmed by chemical and spectroscopic (IR, 1H‐NMR, 13C‐NMR, MS) methods.

Uber die drei discotischen Mesophasen der scyllo-Inosithexaester / On the Three Discotic Mesophases of scyllo-Inositol Hexaesters

Abstract The mesophases of eleven homologous hexaesters ( 1b -1) of the naturally occurring scylloinositol (1a ) representing the first series of alicyclic saturated discogens are studied by calorimetry and optical microscopy. The three derivatives 1 b -d of this hexahydroxy cyclohexane with each six acetyl, propionyl or butyroyl side chains, respectively, exhibit a very organized discophase D1. The hexa-0-acetyl-scyllo-inositol (1b , range of mesophase: Δt = 4.8 °C!) is the discogen having the shortest identical ester groups as lateral functions so far reported for discotic liquid crystals. The pentanoyloxy com pound (1e) exhibits a monotopic D0 mesophase and an enantiotropic optically isotropic and, probably, cubic mesophase D0 different from the smectic D mesophase. Versus increasing temperature the phase sequences are D1 → DE and D1 → D0. Examples of mutual orientation of D1 and DE discophases and binary mixtures exhibiting stable DE discophase at room temperature are also reported. The mesophases of seven more compounds (1f-1) of the homologous series having lateral functions larger than pentanoyloxy are identified by total miscibility as discophase DE. Their stable temperature ranges are very wide e.g. hexa-0-heptanoyl-scyllo- inositol (1g , Δt = 132 °C) which are exceeded only by those discogens having much larger “cores” (up to now of aromatic character only).

Cyclic acetals as carbonyl blocking groups in the photo-fries rearrangement of acyl substituted aryl esters.

The ethylene acetals of o and p -acetoxyacetophenone 3a,b, prepared from the corresponding hydroxyacetophenones by treatment with acetic anhydride in pyridine and subsequently with ethylene glycol and p -toluenesulphonic acid, give upon irradiation the expected photo-Fries products 4a,b (from 3a) or 6 (from 3b). These compounds are converted in part into diacetylphenols 5a,b as a consequence of a deacetalization, occurring to some extent during the irradiation and further in the chromatographic workup. The yields of the photoproducts and the ortho / para ratio (in the case of 3a) are very similar to those given in the literature for phenyl acetate. By contrast, the acetoxyacetophenones 2a,b do not undergo any appreciable change upon irradiation,showing the deactivating effect of the acetyl side chain. Therefore, it is concluded that cyclic acetals are suitable carbonyl blocking groups in order to circumvent the deactivating effect of acyl substituents on the photo-Fries rearrangement of aryl esters.

A novel method to build acetyl and hydroxyacetyl side-chains in 17-oxosteroids

Nine examples are given of the title process.

Studies on beta-lactam antibiotics. VI. Effect on antibacterial activity of alpha-substituents in the 2-(2-amino-4-thiazolyl)acetyl side chain of a cephalosporin nucleus.

Synthesis and in vitro antibacterial activity of semisynthetic cephalosporins (I) having an alpha-substituted 2-(2-amino-4-thiazolyl)acetyl side chain at the 7-position were described.

Markierung von Acetyl‐Ruthenocen mit 97Ru, 2H oder 3H

AbstractAcetyl‐Ruthenocene was labelled by heating Acetyl‐Ferrocene with 97Rucl3. The tritium labelled compound was gained by exchange in tritium‐water at the acetyl side chain of acetyl‐ruthenocene. In a similar way acetyl‐ferrocene was labelled with deuterium.

Studies on beta-lactam antibiotics V. Effect on antimicrobial activity of 2- and/or 3-methyl group (S) in a cephem nucleus.

Synthesis and effect on antibacterial activity of 2- and/or 3-methyl group(s) in the cephalosporins (4a-c) with (Z)-2-(2-amino-4-thiazolyl)-2-(methoxyimino)acetyl side chain were described.

Synthesis of 4-oxo-1,4-dihydro-6h-furo[3,4-c]pyrazole and 4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-C]pyrazole Systems from Acyl Tetronic and Tetramic Acids

Abstract The reaction of acetyl tetronic acid la with phenylhydrazine had been reported to lead to 3-(1-phenylhydrazonoethyl)-tetronic acid 3, which by ring closure afforded the pyrazole-lactone 5a1. On the other hand, condensation of acetyl tetramic acids 2a,b with phenylhydrazine and methylhydrazine had been described as yielding 4-oxo-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole derivatives 9 via the hydrazones 4 2. The lack of reactivity of the carbonyl of the acetyl side chain towards hydrazines is amazing in view of the affinity shown by this group for reactions with amines 3–5. We therefore reinvestigated these structures and we now wish to present evidence for the formation of 1-substituted-4-oxo-1,4-dihydro-6H-furo[3,4-c]pyrazoles 5 and 6 and 1-substituted-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles 7 and 8 and not 2,4,5,6-tetrahydropyrazoles 9 as previously described 2.

α-epithioketosteroids: conformation and reactivity

In order to correlate reactivity with geometry, the conformational analysis of 16,17α-epithiopregnenolone has been carried out using X-ray analysis, low-temperature circular dichroism and quantum chemical calculation. Lack of conformational homogeneity of the acetyl side-chain is revealed; however the conformational equilibrium is restricted to the conformers with relative trans-orientation of epithio- and keto-groups.

Polycyclic hydroxyquinones—VIII: Preparation of acetylhydroxynaphthazarins by photo-fries rearrangement. A convenient synthesis of spinochrome A

Several synthetic routes to mono- and dihydroxynaphthazarins bearing an acetyl side-chain have been explored. Methoxynaphthazarin 1 has always been the starting material. Acylation is brought about via a photo-Fries rearrangement of various adequately substituted acetoxynaphthalenes prepared in several steps from 1. Further steps including oxidative demethylation, hydrolysis and ether cleavage reactions, led to the desired mono- and dihydroxysubstituted acetylnaphthazarins. A new synthesis of Spinochrome A 24, a natural occurring pigment representative of this kind of naphthazarin derivatives, is described.

Hydration and hydrogenation of acetylenic side-chains at the 4- or 5-position of isoxazoles.

Hydration of 5-isoxazolyl-phenyl (or -butyl) acetylenes (1a, b) in dilute sulfuric acid in the presence of mercuric sulfate afforded 5-isoxazolylmethyl phenyl (or butyl) ketones (3a, b), predominantly. In contrast, the hydration of 4-isoxazolyl-phenyl (or -butyl)-acetylenes (2a-d) under identical conditions gave 4-isoxazolyl benzyl (or pentyl) ketones (5a-d) as the main products. The structure of one of these products, 3, 5-dimethyl-4-isoxazolyl benzyl ketone (5a), was determined by Beckmann rearrangement. Isoxazoles containing a cis-alkene or alkane chain were obtained by the catalytic reduction of the above acetylenes without cleaving the isoxazole nucleus.

Structure - activity relationship of melatonin analogues

Analysis of the structure-activity relationship between twenty-three indoleamines and melatonin, based on a specific in vivo fish bioassay, is described. The results clearly define that only halogenation at position 6 or extension of the acetyl side-chain to propionyl or butyryl is tolerated without a decrease in activity. Removal of the indole double bond however, only leads to a less than ten-fold loss of activity. The over-all relevance of the data in the development of a metabolically stable melatonin agonist is discussed.

The heme environment of leghemoglobins Absorption and circular dichroism spectra of artificial leghemoglobins and myoglobins

Artificial leghemoglobins were reconstituted from apoleghemoglobin and meso-, deutero- and diacetyldeuteroheme. Absorption and circular dichroism spectra of their high-spin and low-spin derivatives in the ferrous and ferric forms were recorded in the ultraviolet and visible wavelength regions. The substitution of the 2,4-side-chains of heme induced changes in the optical activity, reflecting alterations in the heme environment. The effect on the conformation of aromatic amino acid residues around heme obviously correlates with the sixth axial ligand and the spin state of iron. Absorption and CD spectra of the aquoferric derivatives of artificial myoglobins were recorded in comparison. Strongly electron-withdrawing acetyl side-chains at the 2,4-positions of diacetyldeuteroheme caused a change in the absorption spectra of aquoferric leghemoglobin and myoglobin towards low spin. On the basis of the spectra it was suggested that the displacement of the ferric iron from the pyrrole plane in leghemoglobin derivatives would be smaller than in the corresponding myoglobin derivatives.

ChemInform Abstract: STUDIES ON QUINOLINE AND ISOQUINOLINE DERIVATIVES. II. COUPLING REACTION OF HALOQUINOLINES AND HALOISOQUINOLINES WITH MONOSUBSTITUTED ACETYLENES IN THE PRESENCE OF PALLADIUM COMPLEX

AbstractAus den Halogenchinolinen (I) entstehen in Gegenwart eines Palladiumkomplexes mit Acetylenen (II) die Alkinylchinoline (III).

Studies on quinoline and isoquinoline derivatives. II. Coupling reaction of haloquinolines and haloisoquinolines with monosubstituted acetylenes in the presence of palladium complex.

The quinoline, isoquinoline, and acridine derivatives containing an acetylenic side chain at the pyridine moiety were synthesized by means of coupling reaction of alkyl (or phenyl) acetylenes with the corresponding halogeno derivatives in the presence of a palladium triphenylphosphine complex.

Synthesis of ring 14C‐methyl labeled retinyl acetate

AbstractA method for incorporation of a 14C‐label in the ring geminal methyl moiety of Vitamin A is described. The procedure involves mono methylation of 2,6‐dimethylcyclohexanone with 14C‐methyl iodide as catalyzed by potassium hydride to afford 2‐14C, 2,6‐trimethylcyclohexanone. Subsequent condensation with an 11‐carbon acetylenic side chain, followed by reduction, acetylation and dehydration yielded 14C‐retinyl acetate. Final purification was achieved by preparative thin layer chromatography.

Studies on pyrimidine derivatives. IX. Coupling reaction of monosubstituted acetylenes with iodopyrimidines.

The pyrimidine derivatives containing an acetylenic side chain were synthesized by means of the reaction of alkyl-(or phenyl) acetylenes with twelve kinds of 2-, 4-, and 5-iodopyrimidines in the presence of a palladium triphenylphosphine complex in satisfactory yields. When propargyl alcohol was used, the reaction exhibited the tendency of decreasing the yield. The reaction readily proceeded in both 2, 4-diiodo- and 4, 6-diiodo-pyrimidines to give the corresponding dialkynyl derivatives. This acetylene coupling reaction was applicable to the synthesis of the 4-quinazoline derivatives.