Dithioacetal Research Articles

Hypervalent Iodine in Synthesis; 5.1The Reaction Between Diaryliodonium Salts and Thiocarboxylic Acid Salts: A Convenient Method for the Synthesis ofS-Aryl Thiocarboxylates

A convenient method for the synthesis of S-aryl thiocarboxylates by the S-arylation of potassium thioacetate or potassium thiobenzoate with diaryliodonium chlorides or iodides in dimethylformamide is reported

Site‐directed chemical conversion of serine to cysteine in penicillin acylase from Escherichia coli ATCC 11105

Penicillin acylase (EC 3.5.1.11) was completely inactivated with equimolar phenylmethane [35S]sulphonyl fluoride (PhMe35SO2F); the stability of the sulphonyl group in the modified protein was determined by measurement of the radioactivity in ultrafiltrates. In 8 M urea, the rate of loss of the sulphonyl group was similar to that observed in PhMeSO2F-inactivated chymotrypsin [Gold, A.M. & Fahrney, D. (1964) Biochemistry 3, 783-791]. Incubation of the PhMeSO2F-inactivated acylase with 0.7 M potassium thioacetate yielded an acetylthiol enzyme which was subsequently converted to a thiol-enzyme during incubation with 10 mM 6-aminopenicillanic acid. 4-Pyridyl-ethylcysteine was released by acid hydrolysis after reaction of the thiol-protein with 4-vinylpyridine. The rates of reaction of thiol-penicillin acylase with iodoacetic acid and 2,2'-dipyridyl disulphide were consistent with the presence of an incompletely accessible cysteinyl sidechain. After carboxymethylating the thiol-enzyme with iodo[2-3H]acetic acid, the label was shown by SDS/PAGE and sequencing analysis to be associated exclusively with the beta-chain NH2-terminal residue, indicating conversion of Ser290 to S-carboxymethyl-cysteine. Near-ultraviolet CD spectra showed the conformation of thiol-penicillin acylase to be indistinguishable from that of the native protein but the catalytic activity was less than 0.02% of that of the normal enzyme. The possibility that Ser290 acts as a nucleophile in catalysis is discussed.

ChemInform Abstract: Selective Reduction‐Acetylation of Azido Sugars Using a Mixture of Thioacetic Acid and Potassium Thioacetate.

ChemInform Abstract: Selective Reduction‐Acetylation of Azido Sugars Using a Mixture of Thioacetic Acid and Potassium Thioacetate.

Total synthesis of analogues of the β-lactam antibiotics. Part 5. 3-Thiacepham-4-exo-carboxylates and their 1,1,3,3-tetraoxides

t-Butyl hydroxy{4-[(Z)-2-(methoxycarbonyl)vinylthio]-2-oxoazetidin-1-yl}acetate (19a) was transformed into t-butyl 2-endo-methoxycarbonylmethyl-3-thiacepham-4-exo-carboxylate (20a) by sequential reactions involving thionyl chloride, potassium thioacetate, and cyclohexylamine. Oxidation of compound (20a) with potassium permanganate gave the 1,1,3,3-tetraoxide (23a), the structure of which was established by X-ray crystallography. The exceptional acidity of the 2- and 4-hydrogen atoms of compound (23a) was revealed by their replacement with deuterium atoms in the presence of deuterium oxide and with methyl groups in the presence of diazomethane. Cleavage of the t-butyl ester function of the thiacepham tetraoxide (23a) was effected by trifluoroacetic acid but the resultant acid (23b) underwent a rapid decarboxylation in water to give 2-endo-methoxycarbonylmethyl-3-thiacepham 1,1,3,3-tetraoxide (26a).

Synthetic Studies on Sialoglycoconjugates. 4: Synthesis of 5-Acetamido-3,5-Dideoxy-d-Galacto-2-Octulosonic Acid Derivatives and Analogs

Abstract 5-Acetamido-3.5-dideoxy-D-galacto-2-octulosonic acid derivatives and the α-2-thioanalog (14) were synthesized. Methyl [2-(trimethylsilyl)ethyl 5-acetamido-3,5-dideoxy-α-D-galacto-2-octulopyranosid]onate (8), prepared from methyl [2-(trimethylsilyl)ethyl 5-acetamido-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosid]onate (1) via 8,9-O-isopropylidenation, O-acetylation, O-deisopropylidenation, metaperiodate oxidation, and sodium borohydride reduction, was converted, by selective bromination, into the 8-bromo derivatives (9). Compound 12, derived from 8 via O-acetylation and boron trifluoride etherate treatment, was converted to the 2-chloro derivative (13), which underwent displacement with potassium thioacetate, to yield methyl 5-acetamido-4,7,8-tri-O-acetyl-2-S-acetyl-2-thio-α-D-galacto-2-octulopyranosonate (14).

The reaction between arenediazonium tetrafluoroborates and alkaline thiocarboxylates in DMSO: A convenient access to aryl thiolesters and other aromatic sulfur derivatives.

The reaction between potassium thioacetate or sodium thiobenzoate and arenediazonium tetrafluoroborates in DMSO leads to the corresponding aryl thiolesters 1 which can either be isolated or further reacted providing a convenient one-pot access to a number of other aromatic sulfur derivatives.

An azidoaryl thioglycoside of sialic acid. A potential photoaffinity probe of sialidases and sialic acid-binding proteins

An azidoaryl thioglycoside of sialic acid was prepared, as a potential photoaffinity probe reagent for the analysis of sialidases and sialic acid-binding proteins, by treatment of the glycosyl chloride of N-acetylneuraminic acid methyl ester with potassium thioacetate to give, in 70% yield, methyl 5-acetamido-4,7,8,9-tetra- O-acetyl-2- S-acetyl-2,3,5-trideoxy-2-thio-α- d- glycero- d- galacto-2-nonulopyranosonate. Selective hydrolysis of the thioacetate ester, followed by condensation with 4-fluoro-3-nitrophenyl azide, O-deacetylation, and hydrolysis gave (4-azido-2-nitrophenyl)- 5-acetamido-2,3,5-trideoxy-2-thio-α- d- glycero- d- galacto-2-nonulopyranosidonic acid.

ChemInform Abstract: Polyethylene Glycols as Solvents for Anionic Activation: Synthesis of Thioacetates by Means of Potassium Thioacetate in Polyethylene Glycol 400.

AbstractThe allylic halides or sulfonates (I) react with potassium thioacetate (II) in polyethylene glycol 400 to produce the thioacetates (III) which yield the corresponding thiols (IV) upon hydrolysis.

A convenient method for S-glycosidic bond formation. Synthesis of p-lodophenyl 4′-thiomaltotrioside and its 2″,3″-unsaturated analogue

The axial trifluoromethanesulphonate group at C-4′ of acylated galactopyranosylglucopyranoside (11) was substituted by sulphur nucleophiles: selective S-deacetylation and activation of peracetylated 1-thio-α-D-glucose (12) led to p-iodophenyl 4′-thiomaltotrioside derivative (13); substitution by potassium thioacetate and S-deacetylation afforded 4′-thiomaltoside (17) which gave, by condensation with acetylated 1,5-anhydro-2-deoxy-D-arabino-hex-1-enitol, under acidic conditions, as a major product the 2″,3″-unsaturated trisaccharide (19). The synthesis of compound (2), the sulphur positional isomer of (1), in 73% yield is also reported.

The reactivity of sulfur nucleophiles towards arenediazonium tetrafluoroborates in aprotic solvents: Synthesis of S-aryl thioacetates

Various S-aryl thioacetates are prepared in 40-60% yield by treatment of arenediazonium tetrafluoroborates with commercial potassium thioacetate in DMSO at room temperature.

A photoreactive competitive inhibitor of the human lysosomal neuraminidase in cultured skin fibroblasts

A photoreactive, potent, competitive inhibitor of the human lysosomal neuraminidase in cultured skin fibroblasts has been prepared. The starting material, 2,3 dehydro-N-acetyl neuraminic acid methyl ester, was selectively tosylated at the C-9 position with tosyl chloride and subsequently peracetylated with acetic anhydride. The tosyl group was displaced with potassium thio acetate in dimethylformamide at 60 degrees C for 80 min. 4-fluoro-3-nitrophenylazide was incorporated by reaction with the thio acetate product and equimolar sodium methoxide in methanol followed by reacetylation. Base hydrolysis gave the final product, 9-S-(4-azido-2-nitrophenyl)-5-acetamido-2,6 anhydro-2,3,5,9-tetradeoxy-9-thio-D-glycero-D-galacto-non-2-enonic acid (W5). The yields at each step were 50-70%. Competitive inhibition kinetics were observed when W5 was tested with the fibroblast neuraminidase using 4-methylumbelliferyl-N-acetyl-neuraminic acid as substrate giving an apparent Ki of about 10 microM. These results suggest that the terminal hydroxyl group at C-9 may not be important in the recognition and binding of the substrate by the enzyme. Also, the compounds prepared here may be useful as photoaffinity probes or ligands for affinity chromatography for purification.

Polyethylene Glycols as Solvents for Anionic Activation: Synthesis of Thioacetates by Means of Potassium Thioacetate in Polyethylene Glycol 400

Abstract Recently, polyethylene glycols (PEGS) of various molecular weights have been proposed as solvent promoters for various reactions 1, 2. We wish to report on the use of PEG 400 as solvent for the anionic activation of potassium thioacetate, which could be used for the preparation of alkyl and benzyl thioacetates from the corresponding halides or alcohol derivatives. The method can be synthetically significant, since from thioacetates the corresponding thiols can be easily prepared under a variety of mild conditions 3.

ChemInform Abstract: SYNTHESIS OF PYRIDAZINO(4,5‐E)(1,3,4)THIADIAZINES AND THE RING CONTRACTION TO PYRAZOLO(3,4‐D)PYRIDAZINES THROUGH EXTRUSION OF SULFUR

AbstractDie Cyclisierung der aus den Pyridazinonen (I) dargestellten Verbindungen (II) führt zu den Thiadiazinen (III), die zu (IV) deacetyliert werden.

Synthesis of acylthioester phospholipids and their hydrolysis by phospholipase A 2

This paper describes the synthesis of short-chain phospholipid analogs with an acylthioester bond exclusively at the sn-2-position for use in spectrophotometric assays of phospholipase A 2 in the presence of thiolreagents. 1- O-Octyl-2-deoxy-2-S-hexanoyl- sn-glycero-3-phosphocholine (thioC6PC), 1- O-octyl-2-deoxy-2-S-heptanoyl- sn-glycero-3-phosphocholine (thioC7PC), 1- O-octyl-2-deoxy-2-S-hexanoyl- sn-glycero-3-sulfate (thioC6 sulfate) and 1- O-hexadecyl-2-deoxy-2-S acetyl- sn-glycero-3- phosphocholine (thioacetyl PAF) were prepared by total synthesis starting from 1,2-isopropylidene- sn-glycerol. The thioester bond in these substrates was introduced by a Walden-inversion by reacting 1- O(4′-Methoxytrityl)-3- O-octyl-2-tosyl- sn-glycerol with potassium thioacetate. Complete hydrolysis of the substrates by the stereo-specific phospholipase A 2 from porcine pancreas confirmed the expected stereochemical configuration. Although space filling models of thioC7PC showed a great resemblance with those of 1,2-dioctanoyl- sn-glycero-3-phosphocholine (diC8PC) the hydrolysis rate for the thioester substrate was lower by at least two orders of magnitude. Studies with mixed micelles of these two substrates suggest that the reduced hydrolysis rate of thioester is more likely caused by subtle changes in the architecture of the substrate molecules per se than by a decreased quality of the interface.

ChemInform Abstract: SYNTHESIS OF 2‐DEOXY‐3,4‐ANHYDRO‐L‐THREO‐PENTOSE DIETHYL DITHIO ACETAL: A C5 FUNCTIONALIZED CHIRAL EPOXIDE

Chemischer InformationsdienstVolume 15, Issue 9 Natural Products ChemInform Abstract: SYNTHESIS OF 2-DEOXY-3,4-ANHYDRO-L-THREO-PENTOSE DIETHYL DITHIO ACETAL: A C5 FUNCTIONALIZED CHIRAL EPOXIDE C. MORIN, C. MORINSearch for more papers by this author C. MORIN, C. MORINSearch for more papers by this author First published: February 28, 1984 https://doi.org/10.1002/chin.198409321Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume15, Issue9February 28, 1984 RelatedInformation

Synthesis of pyridazino(4,5-e)(1,3,4)thiadiazines and the ring contraction to pyrazolo(3,4-d)pyridazines through extrusion of sulfur.

Cyclization of 2-substituted 5-[(α-bromobenzylidene) hydrazino)]-4-chloro-3 (2H)-pyridazinones (2) with potassium thioacetate, followed by deacetylation, provided new ring system derivatives, 7-substituted 2-phenyl-4H-pyridazino [4, 5-e] [1, 3, 4] thiadiazin-8 (7H)-ones (4). 8-Chloro and 8-amino derivatives (10) of the pyridazinothiadiazine ring were readily derived from 4-acetyl-2-phenyl-4H-pyridazino [4, 5-e] [1, 3, 4] thiadiazin-8 (7H)-one (3d) by chlorination and subsequent amination. Ring contraction of the 8-oxo derivatives (4) to 5-substituted 3-phenyl-1H-pyrazolo [3, 4-d] pyridazin-4 (5H)-ones (6), through extrusion of sulfur under basic or thermal conditions, was observed. A similar reaction occurred in the case of the 8-chloro and 8-amino derivatives (10). Probable mechanisms for these reactions and differences of reactivity between 4 and 10 are discussed.

Synthesis ofN-[2-S -(2-Acetamido-2,3-dideoxy-D-glucopyranose-3-y1)-2-Thio-D-Lactoyl]-L-alanyl-D-isoglutamine

Abstract N-[2-S-(2-Acetamido-2,3-dideoxy-D-glucopyranose-3-y1)-2-thio-D-lactoyl]-L-alanyl-D-isoglutamine, in which the oxygen atom at C-3 of N-acetylmuramoic acid moiety in N-acetylmuramoyl-L-alanyl-D-isoglutamine (MDP) has been replaced by sulfur, was synthesized from allyl 2-acetamido-2-deoxy-β-D-glucopyranoside (1). Treatment with sodium acetate of the 3-O-mesylate, derived from 1 by 4,6-O-isopropylidenation and subsequent mesylation, gave allyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-β-D-allopyranoside (4). When treated with potassium thioacetate, the 3-O-mesylate, derived from 4, afforded allyl 2-acetamido-3-S-acetyl-2-deoxy-4,6-0-isopropylidence-β-D-glucopyranoside (6). S-Deacetylation of 6, condensation with 2-L-chloropropanoic acid, and subsequent esterification, gave the 3-s[D-1(methoxycarbonyl)ethyl]-3-thio-glucopyranoside derivative (7). Coupling of the acid, derived from 7, with the methyl ester of L-alanyl-D-isoglutamine, and subsequent hydrolysis, yielded the title compound.

Synthesis and biological activities of N-acetyl-1-thiomuramoyl- l-alanyl- d-isoglutamine and some of its lipophilic derivatives

N-Acetyl-1-thiomuramoyl- l-alanyl- d-isoglutamine and some lipophilic analogs were synthesized from benzyl 2-acetamido-2-deoxy-4,6- O-isopropylidene-3- O-[ d-1-(methoxycarbonyl)ethyl]-α- d-glucopyranoside ( 1). O-Debenzoylation of 2, derived from 1 by oxidation, gave 2-acetamido-2-deoxy-4,6- O-isopropylidene-3- O-[ d-1-(methoxycarbonyl)ethyl]- d-glucopyranose ( 3). Condensation of the alkoxytris(dimethylamino)phosphonium chloride ( 4), formed from 3 by the action of carbon tetrachloride and tris(dimethylamino)phosphine, with potassium thioacetate afforded 2-acetamido-1- S-acetyl-2-deoxy-4,6- O-isopropylidene-3- O-[ d-1-(methoxycarbonyl)ethyl]-1-thio-β- d-glucopyranose ( 8). Coupling of the acid 9, obtained from 8 by hydrolysis and subsequent S-acetylation, with the methyl ester of l-alanyl- d-isoglutamine gave N-[2- O-(2-acetamido-1- S-acetyl-2,3-dideoxy-4,6- O-isopropylidene-1-thio-β- d-glucopyranose-3- yl)- d-lactoyl]- l-alanyl- d-isoglutamine methyl ester ( 10), which was converted, via O-deisopropylidenation, S-deacetylation, and de-esterification, into the N-acetyl-1-thiomuramoyl dipeptide. Condensation of 11 (derived from 10 by S-deacetylation) and of 12 (obtained from 10 by S-deacetylation and de-esterification) with various acyl chlorides yielded the corresponding 1- S-acyl- N-acetylmuramoyl- l-alanyl- d-isoglutamine derivatives, which were converted into the desired, lipophilic 1-thiomuramoyl dipeptides by cleavage of the isopropylidene group. Condensation of 11 with the alkyl bromides yielded the 1- S-alkyl derivatives, which were also converted, via O-deisopropylidenation and de-esterification, into the corresponding 1- S-alkylmuramoyl dipeptides. The biological activities were examined in guinea-pigs and mice.

ChemInform Abstract: THE SYNTHESIS OF 4‐DECARBOXY‐4‐PHOSPHONO‐O‐2‐ISOOXACEPHEMS, ‐ISOPENAMS AND ‐ISOOXACEPHEMS CONTAINING PHOSPHORUS AT THE 3‐POSITION

AbstractZwei neue Typen von Isooxacephemen, die Verbindungen (VI) und (VIII), in denen eine Phosphonatgruppe entweder eine Carboxylgruppe bzw. das C(3)‐Atom ersetzt, werden wie aufgezeichnet dargestellt.

Synthesis of 3-O-(6-deoxy-6-sulpho-α-D-glucopyranosyl)-1,2-di-O-hexadecanoyl-L-glycerol, ‘sulphoquinovosyl diglyceride’

3-O-(2,3,4-Tri-O-benzyl-6-O-tosyl-α-D-glucopyranosyl)-1,2-O-isopropylidene-L-glycerol was treated with potassium thioacetate and the product was hydrolysed with base to give the corresponding 6-deoxy-6-thioderivative which on oxidation with iodine gave the crystalline disulphide. The isopropylidene groups were hydrolysed and the product was acylated with hexadecanoyl chloride in pyridine to give crystalline bis-[3-O-(2,3,4tri-O-benzyl-6-deoxy-α-D-glucopyrancsyl)-1,2-di-O-hexadecanoyl-L-glycerol]-6,6-disulphide. Oxidation of this compound with 3-chloroperbenzoic acid and subsequent hydrogenolysis of the benzyl groups gave the title compound with properties similar to those of a sample prepared by hydrogenation of the natural ‘sulphoquinovosyl diglyceride.’