Acetylation Shifts Research Articles

ChemInform Abstract: Synthesis and Evaluation of Antiviral Activity of L-Acosamine and L- Ristosamine Nucleosides of Furanose Configuration.

Mercuric-catalyzed hydrolysis of acetylated L-rhamnal 1 gives an alpha,beta-unsaturated aldehyde 2. 1,4-Addition of DBU-phthalimide salt with concomitant acetyl shift resulted in L-ribo and L-arabino isomers of 5-O-acetyl-2,3,6-trideoxy-3-phthalimido-hexofuranose 3 and 4. After acetylation at the anomeric center, coupling with silylated thymine resulted in three new nucleosides, with L-acosamine and L-ristosamine of furanose configuration as the carbohydrate moiety. The target compounds have been evaluated for their antiviral activity against HIV and HSV-1.

The reaction of some endo-5-acetyl norborn-2-enes with benzene thiol: a thermally induced non-allylic [1,3]-acetyl shift, as anticipated by a photochemical precedent

The thermal reaction of benzene thiol with rac-1-(4aS*,5R*,8S*,8aR*-5,8-methano-1,2,3,4,4a,5,8,8a-octahydro-4a-naphthyl)ethanone (10b), an endo-5-acetylnorborn-2-ene with a particularly close distance between one olefinic carbon and the keto carbon, and with its 8aS* epimer 10a, has been investigated. Besides the conventional unrearranged adducts 16a, b and 17a, b of the thiol to the C=C bonds of 10a, b, an adduct 18 was formed from 10b that involved a [1,3]-acetyl shift; no other products were formed. The dependence of adduct ratios on thiol concentration is consistent with two competing reactions of an intermediate radical 14b formed by addition of thiyl radical to the C=C bond of 10b, namely, abstraction of hydrogen from thiol (which is the conventional reaction path) vs. intramolecular attack of the radical on the keto group inducing the [1,3] shift of the latter. This shift constitutes an intramolecular variety of the known alkyl transposition reaction of ketones initiated by a reversible attack of an alkyl radical on a keto carbonyl group to generate an intermediate tert-alkoxyl radical; however, it is very much faster than the intermolecular reaction and corresponds to an effective molarity between 107 and 1010. These findings have a bearing on the mechanism of photorearrangements homologous to the ODPM (oxa-di-π-methane) photorearrangement, such as ODPE (oxa-di-π-ethane) and higher homologues, in that they support a two-step mechanism involving this type of acyl shift. Keywords: oxadi-π-methane photorearrangement; oxadi-π-ethane photorearrangement; acetyl shift, non-allylic [1,3]; thiol, addition to C=C bonds; norbornenes.

Synthesis of 3′‐Amino‐2′,3′‐dideoxy‐hexofuranose Nucleosides with Potential Anti‐Viral Activity

Michael type addition of DBU (1,8-diazabicyclo[5,4,0]undec-7-ene) phthalimide salt to 4,6-di-O-acetyl-2,3-dideoxy-aldehydo-D-erythro-trans-hex-2-enos e 2 and concomitant acetyl shift give an anomeric mixture of arabino and ribo isomers of 5,6-di-O-acetyl-2,3-dideoxy-3-phthalimido-D-hexofuranose 3 which after acetylation at the anomeric hydroxy group is separated to give 4 and 5. Subsequent reaction with 5'-substituted silylated uracil in the presence of TMS-triflate results in three different 5',6'-di-O-acetyl-2',3'-dideoxy-3'-phthalimido-D-hexofuranose nucleosides 7, 9, and 10 which were deprotected to give the corresponding 3'-amino nucleosides 8, 11, and 12. The compounds 7-12 were investigated for their activity against HSV-1 and HIV-1.

Synthesis and evaluation of antiviral activity of L-acosamine and L-ristosamine nucleosides of furanose configuration.

Mercuric-catalyzed hydrolysis of acetylated L-rhamnal 1 gives an alpha,beta-unsaturated aldehyde 2. 1,4-Addition of DBU-phthalimide salt with concomitant acetyl shift resulted in L-ribo and L-arabino isomers of 5-O-acetyl-2,3,6-trideoxy-3-phthalimido-hexofuranose 3 and 4. After acetylation at the anomeric center, coupling with silylated thymine resulted in three new nucleosides, with L-acosamine and L-ristosamine of furanose configuration as the carbohydrate moiety. The target compounds have been evaluated for their antiviral activity against HIV and HSV-1.

1H and 13C NMR assignments for lanostan‐3β‐ol derivatives: Revised assignments for lanosterol

Abstract1H and 13C NMR assignments are presented for 30 oxygenated lanostane derivatives, including lanosterol, dihy‐drolanosterol, 7‐ketolanosterol, agnosterol, 24,25‐epoxylanosterol, 8α,9α‐epoxylanostan‐3β‐ol, three 15‐oxygenated derivatives of lanost‐7‐en‐3β‐ol, lanostane‐3β,7α‐diol, lanostane‐3β,9α‐diol and their acetates. These assignments, which were largely determined by a combination of DEPT, one‐boad and long‐range 13C1H chemical shift correlation and lanthanide‐induced shift experiments, are not dependent on previously reported assignments, several of which were found to be incorrect. 1H and 13C acetylation shifts for lanostan‐3β‐ols were sufficiently invariant among the sterols studied that they were useful for assigning carbons in rings A and B. The acetylation shifts reported for lanostan‐3β‐ols were extended and partially revised.

13C NMR shifts and conformations of substituted indans

Abstract13C NMR spectra of indan derivatives bearing substituents in the 1, 2, 5 and 6 positions are reported and assigned by LIS measurements and other techniques. Epimeric indanes bearing vicinal oxygen and phenyl or benzyl substituents show ring carbon shielding in the cis relative to the trans isomers, which is compared with corresponding cyclopentane shifts, and indicates the predominance of envelope conformations with pseudoaxial oxygen substituents for the cis isomers. Acetylation shifts show consistently larger shielding at C‐β for the trans compounds. Introduction of oxygen at C‐5 leads to asymmetric shielding effects at the ortho carbon atoms as soon as there is a substituent in the para position which can participate in mesomeric forms.

1,5] and [1,2] Acetyl shifts in Diels–Alder adducts of 2-acetyl-6-methyl-1,4-benzoquinone

Treatment of the Diels–Alder adduct 4a-acetyl-4a,5,8,8a-tetrahydro-3-methyl-1, 4-naphthoquinone with pyridine–methanol or acetic anhydride leads to a [1,5] acetyl shift to the 3-position which can be followed by a [1,2] acetyl shift to the 2-position (adduct numbering).

13C NMR studies of some complex natural oxygen heterocyclics : Structure of millettin, a novel isoflavone isolated from Millettia Auriculata

13C NMR spectra for a variety of isoflavones are presented and analysed. The novel isoflavone, Millettin (Xa) is shown to be closely related to Auriculatin (II). While comparison of the 13C NMR spectra did not readily prove the orientation of the fused pyran ring, the use of acetylation shifts showed unambiguously that the fusion in linear, rather than angular.

Acetylation of Prostaglandin Endoperoxide Synthetase with Acetylsalicylic Acid

Incubation of purified prostaglandin endoperoxide synthetase from sheep vesicular glands with aspirin results in a covalent binding of the acetyl group of acetylsalicylic acid to the protein. During this acetylation, the cyclooxygenase activity is lost, but not the peroxidase activity. The reaction is completed when almost one acetyl group is bound per polypeptide chain (Mr = 68 000). After proteolysis of [3H]acetyl-protein with pronase, radioactive N-acetylserine was obtained. Originally, however, the hydroxyl group of an internal serine residue in the chain is acetylated. The formation of N-acetylserine can be explained by a rapid O leads to N acetyl shift as soon as the NH2 group of serine is liberated. A radioactive dipeptide was isolated from a thermolysin digest of the [3H]acetyl-enzyme containing phenylalanine and serine, phenylalanine being its N-terminal amino acid. Automatic Edman degradation of native and acetylated enzyme showed that only one polypeptide sequence was present: Ala-Asp-Pro-Gly-Ala-Pro-Ala-Pro-Val-Asn-Pro-X-X-Tyr-. The N-terminal sequence has an apolar character.

Model of interaction of ajmaline with polyvinylpyrrolidone

The chemical shifts in the Fourier transform 13C-NMR spectrum of ajmaline were assigned from consideration of the acetylation shifts and multiplet splitting in the off-resonance decoupled spectrum. On the basis of the assigned signals, the changes of chemical shifts in ajmaline induced by polyvinylpyrrolidone were investigated, and an interaction model of ajmaline with polyvinylpyrrolidone in chloroform was proposed.

The structure of the antibiotic hedamycin—III: 13C NMR spectra of hedamycin and kidamycin

The 13C NMR spectra of hedamycin, kidamycin and some of their derivatives have been fully assigned. Proton coupling constants and 13C NMR acetylation shifts indicate that the conformations of the highly substituted tetrahydropyran rings in solution are chair forms for ring E, as well as for ring F in isokidamycins, but a twist form for ring F in hedamycins and kidamycins.

The carbinyl acetylation shifts: A potential tool for differentiating the conformations of secondary allylic alcohols on six-membered rings

The carbinyl acetylation shifts: A potential tool for differentiating the conformations of secondary allylic alcohols on six-membered rings

Relationship between structure and chemical reactivity in d-glyceraldehyde 3-phosphate dehydrogenase. Trinitrophenylation of the lysine residues in yeast, sturgeon and rabbit muscle enzyme

From the modification of the lysine residues of yeast and sturgeon muscle glyceraldehyde 3-phosphate dehydrogenase by 2,4,6-trinitrobenzene sulphonate the following results are obtained. 1. (a) In the absence of NAD + 1.1. (i) The trinitrophenylation follows a biphasic process. During the first phase two and four lysine residues are modified with a loss of 50% and 80% of the dehydrogenase activity in sturgeon muscle enzyme and yeast enzyme, respectively. 1.2. (ii) The modification of these more reactive lysine residues has very little effect on the K m of d-glyceraldehyde 3-phosphate, NAD + or arsenate; only V m is decreased; however, the esterase activity measured with p-nitrophenol acetate remains at about 85% of the initial activity. 1.3. (iii) The trinitrophenylation of these lysine residues in the yeast enzyme abolishes almost totally the S → N acetyl shift from cysteine 149 to lysine 183, whereas in the muscle apoenzymes it is partially prevented. 2. (b) In the presence of NAD + 2.1. (i) With the sturgeon muscle enzyme the trinitrophenylation is a first-order reaction and the loss of activity follows a first-order process, results which are similar to those obtained with the rabbit muscle enzyme (Foucault et al., 1974). Moreover, the rate of trinitrophenylation of lysine residues is identical to the rate of trinitrophenylation of the “slow” reacting lysine residues of apoenzyme, thus indicating that only the most reactive lysine residues are protected by the conformational change induced in the protein by the coenzyme. 2.2. (ii) With the yeast enzyme, trinitrophenylation of the holoenzyme still follows a bipliasic process; however, both rates are decreased as compared with the apoenzyme. The conformational changes induced by NAD + affect the reactivity of both classes of lysine residues. 3. (c) From the common effects of the trinitrophenylation of the most reactive lysine residues on the enzyme activity of the three dehydrogenases, as well as on the specific S → N acetyl transfer with acetylphosphate, it seems that the same lysine residues are being modified and that these might be either lysine 183 or lysine 191, which is located in the proximity. 4. (d) The difference in the number of lysine residues that are trinitrophenylated in the first phase of the chemical modification of the yeast and muscle enzymes is related either to the geometrical disposition of the subunits in the oligomeric structure or to the distance between the active centre regions which are face to face in the dimers (Buehner et al., 1974).

Carbon-13 nuclear magnetic resonance spectra of vitamins D and related compounds.

1. The natural abundance carbon-13 nmr of vitamins D (D2 and D3) and several isomers (5, 6-trans-vitamin D2, isotachysterol2 and isovitamin D2) have been completely assigned by employing off-resonance noise-decoupling, acetylation shifts, and lanthanide-induced shifts experiments. The last two techniques were especially useful for the present study. 2. Carbon-13 nmr spectral characteristics of the three main conjugated triene moieties (SE-Z-SZ, SE-E-SZ, or SE-E-SE), involved in the molecules of vitamin D and its isomers, were revealed. Thus, the striking dependence of the shieldings on molecular geometries and high sensitivity of the resonances to the environments of conjugated systems were surveyed. 3. Conformational preferences in solutions of the hydroxyl groups in vitamins D2 and D3 as well as 5, 6-trans-vitamin D2 were conveniently determined.

13C nuclear magnetic resonance spectra of some ergosta-dienes and -trienes

The natural abundance 13C spectra of several ergosta-dienes and -trienes, measured at 25·2 MHz, have been completely assigned by using off-resonance decoupling, acetylation shifts, and lanthanide-induced shifts. The effect of functional groups on the chemical shifts is highly sensitive to the environments of the functional group and the carbon atom under consideration, and analogies from simpler systems (e.g. cyclohexanes) are not always reliable.

Austocystins. Six novel dihydrofuro[3′,2′:4,5]furo[3,2-b]xanthenones from Aspergillus ustus

Extraction of maize meal cultures of Aspergillus ustus gave six novel metabolites, designated austocystins, to which were assigned the substituted 3a, 12a-dihydrofuro[3′,2′:4,5]furo[3,2-b]xanthen-5-one structures (1), (20), (21), (23), (26), and (29). The substitution pattern of the austocystins was confirmed by the results of chemical degradation as well as by use of n.m.r. techniques such as acetylation shifts, benzene-induced solvent shifts, and nuclear Overhauser effect experiments.

The association of the Claisen rearrangement with a novel [1,5] sigmatropic rearrangement

Thermal rearrangement of the allyl aryl ether (5) gave, in addition to the expected Claisen rearrangement product (6), the isomer (7), and similarly thermal transformation of the allyl ether (8) gave the mixture (9) and (10); the formation of (7) and (10) is rationalised as involving a [1,5] acetyl shift.

An Attempt to Convert Glycine Residues to Threonine Residues in Polyglycine

Abstract When polyglycine was reacted with acetaldehyde in liquid ammonia in the presence of metallic sodium, it was observed that 7∼9% of the threonine residues were formed from glycine residues. From the hydrolyzate of the modified polyglycine, threonine could be isolated by the aid of the O→N acetyl shift reaction. It was shown that the threonine thus isolated was 35.6% allothreonine.

O→N-Acetyl Shift of O-Acetylserine and O-Acetylthreonine. An Approach to the Separation of Serine and Threonine Fraction from Amino Acid Mixture

Abstract The reaction rate of O→N-acetyl shift of O-acetylserine was compared with that of O-acetylthreonine, and it was found that the latter was greater than the former. By utilizing the difference of the rates of the reaction of these amino acid derivatives, an attempt to separate serine and threonine from their mixture was unsuccessful owing to the fact that the shift reaction was affected by many factors, i. e., the ionic strength of inorganic salts present, pH of the reaction medium and the reaction temperature. Serine and threonine were isolated from the acid hydrolyzate of casein through their O-acetylation and subsequent O→N-acetyl migration with 80∼90% yield.