Erich Zbiral

Synthesis of both epimeric 2-deoxy-n-acetylneuraminic acids and their behaviour towards CMP-sialate synthetase-a comparison with 2-β-methylketoside of n-acetylneuraminic acid☆

Methyl-2-β-chloro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate 2 respectively methyl 1-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate 3 were transformed by catalytic hydrogenation or by reduction with tributyltin hydride to the corresponding 2-deoxy derivatives 4 and 5, which gave after saponification the acids 6 and 7. Both epimers are not inhibitors of CMP-sialate synthetase (EC 2.7.7.43), whereas the 2-β-methylketoside of Neu5Ac behaves as a competitive inhibitor of the activation of Neu5Ac (N-acetylneuraminic acid).

On the side-chain conformation of N-acetylneuraminic acid and its epimers at C-7, C-8, and C-7,8☆

The side-chain conformation of N-acetylneuraminic acid and analogs has been studied by n.m.r. spectroscopy. The results of the 1H-, 13C-n.m.r.-, and 1H-nuclear-Overhauser-enhancement measurements were used to distinguish between different local-minima conformations suggested by hard-sphere calculations. Attempts were made to correlate the major conformation determined for each compound with the behavior towards activation with N-acetylneuraminic acid-CMP-synthetase.

Transferreaktionen mit hilfe von phenyl-jodosoacetat—I : Zur reaktion von olefinen mit C6H5J(OAc)2-(CH3)3SiN3☆

Zusammenfassung Mit Hilfe des Systems Phenyljodosoacetat-Trimethylsilylazid (C 6 H 5 J(OAc) 2 -(CH 3 ) 3 SiN 3 ) gelingt es, dreifach verzweigte Olefine oxydativ aufzuspalten, wobei eine Carbonyl- und eine Nitrilfunktion gebildet werden. Aus Δ 5 -Steroiden werden in ubersichtlicher Weise die 5,6-Seco-5-Oxo-6-saurenitrilsteroide gebildet. Diese Spaltungsreaktion ist von synthetischem Wert, weil man sie auch auf die leicht gewinnbaren 1-Alkyl-bzw. 1-Arylcycloalkene ubertragen kann; hier gelangt man unmittelbar zu den entsprechenden ω-Acylcarbonsaurenitrilen RCO(CH 2 ) n CN. Auf Unterschiede gegenuber dem System Pb(OAc) 4 -(CH 3 ) 3 SiN 3 1,2 wird hingewiesen.

2,3-Didehydro-2-deoxysialic acids structurally varied at C-5 and their behaviour towards the sialidase from Vibrio cholerae☆

2,3-Didehydro-2-deoxy-N-trifluoroacetylneuraminic acid (5-trifluoroacetyl-Neu2en) (3) has been synthesised from Neu5Ac2en (1) by hydrazinolysis, to give Neu2en (2), followed by N-trifluoroacetylation. 2,3-Didehydro-2,3-dideoxy-D-glycero-D-galacto-2-nonulopyranoson ic acid (Kdn2en, 8) and 5-azido-2,3-didehydro-2,3,5-trideoxy-D-glycero-D-galacto-2-nonu lopyranosonic acid (5-azido-5-deoxy-Kdn2en, 9) have been prepared from the acetylated methyl esters of Kdn (4) and 5-azido-5-deoxy-Kdn (5) via Zemplén saponification. The behaviour of the above 2,3-didehydro-2-deoxysialic acids towards Vibrio cholerae sialidase has been investigated.

A novel and versatile synthesis of heterocyclic aldehydes using dialkyl 3-oxo-1-alkenyl-phosphonates.

Abstract Dialkyl 1,2-epoxy-3-oxoalkyl-phosphonates, easily prepared from the corresponding 1-alkenyl-phosphonates, react with ambident nucleophiles to dialkyl 1-hetaryl 1-hetaryl-1-hydroxymethyl-phosphonates, which can be transformed to heterocyclic aldehydes.

Reaktionen polyvalenter jodverbindungen—III : Umwandlung von olefinen in α-azidocarbonylverbindungen mit hilfe von C6H5J(OAc)2(CH3)3SiN3

Zusammenfassung Wahrend das System Pb(OAc) 4 (CH 3 ) 3 SiN 3 mit einfachen nucleophilen Olefinen meist Diazide und Azid-acetoxyverbindungen liefert 2 und nur im Falle der Steroidolefine α-Azidoketone, 3 reagiert das Titelreagens sowohl mit nucleophilen als auch mit manchen elektrophilen Doppelbindungen in ubersichtlicher Weise unter Bildung von α-Azidocarbonylverbindungen. Hingegen werden keine Azidacetoxy-verbindungen gebildet. Wie die Verbindung 14 zeigt, scheint eine Aktivierung durch einen Arylrest fur das Gelingen der Reaktion nicht nicht erforderlich zu sein. Ein polarer Ablauf der Reaktion wird fur unwahrscheinlich gehalten.

Strukturelle Abwandlungen an N-Acetylneuraminsäuren, 8 Synthese von 7-, 8-, 9-Desoxy- und 4,7-Didesoxyneuraminsäure

The 7- and 8-Iodnonulosonic acid derivatives1 and2 react with tributyltinhydride-AIBN to the 7- and 8-deoxy-N-acetylneuraminic acid derivatives3 a and4 a which after hydrolysis give the 7-deoxy-N-acetylneuraminic acid3 b (5-N-acetamido-3,5,7-trideoxy-β-D-galacto-2-nonulopyranosidonic acid=7-Deoxy-Neu5Ac) and 8-deoxy-N-acetylneuraminic acid4 b (5-N-acetamido-3,5,8-trideoxy-β-D-galacto-2-nonulopyranosidonic acid=8-Deoxy-Neu5Ac). The 4,8,9-tris-(t-butyldimethylsilyl)-N-acetylneuraminic acid derivative5 a yields after transformation to the 7-O-acetyl compound5 b and partial removing of the protecting groups the derivative5 c. Further reaction with theMitsunobu-reagent and methyliodide affords the 9-Iodocompound6 a which turned to the 8-O-acetylderivative6 b. Subsequent reduction by means of tributyltinhydride yields first the 9-deoxyderivative7 a and after hydrolysis the 9-deoxy-N-acetylneuraminic acid7 b (5-N-acetyl amido-3,5,9-trideoxy-D-glycero-β-d-galacto-2-nonulopy-ranosidonic acid=9-Deoxy-Neu5Ac). Another synthesis of7 b follows the route8 f →8 g →7 c. The Deoxy-N-acetylneuraminic acid3 b could be prepared also by an alternative procedure using the methyl-β-8,9-methylethylen-4-O-t-butyldimethylsilyl-N-acetylneuraminic acid methylester8 a via the intermediate compounds8 d and8 e. Application of the 8,9-O-methylethyliden-N-acetylneuraminic acid derivative8 opens an approach to the xanthogenates8 a and8 b which could be reduced to the deoxy-N-acetylneuraminic acid derivatives9 a and10 a. Hydrolysis of10 a yields the 4,7-dideoxy-N-acetylneuraminic acid10 b (5-N-acetamido-3,4,5,7-tetradeoxy-β-D-lyxo-2-nonulopyranosidonic acid=4,7-Dideoxy-Neu5Ac).

Synthese, Reaktionen und NMR-Spektren von 2-Brom-3-oxo-1-alkenyl- und 3-Oxo-1-alkinyl-phosphonsäure-dialkylestern

Dialkyl (E)-3-oxo-1-alkenylphosphonates (1), on reaction with bromine and subsequent HBr-elimination, yield the isomeric β-bromovinyl derivatives (Z)-3 and (E)-3 and the alkinylphosphonates4. β-Bromovinyl compounds3 can also be obtained by reaction of1 withNBS in aqueous solution. The configuration of the β-disubstituted vinylcompounds is assigned from their13C-NMR spectra. Both bromovinyl compounds3 and alkinylderivatives4 are used for regioselective syntheses of acylsubstituted pyrazolylphosphonates5.

Reactions with organophosphorus compounds, 50. : Trimethylsilylethoxymethylene triphenylphosphorane, a novel reagent for the homologation of carbonyl compounds.☆

Abstract Homologation of aldehydes and ketones is achieved by means of trimethylsilylethoxymethylene triphenylphosphorane.

Interaction ofN-acetyl-4-, 7-, 8- or 9-deoxyneuraminic acids andN-acetyl-4-, 7- or 8-mono-epi- and-7,8-di-epineuraminic acids withN-acetylneuraminate lyase

Various deoxy- and epi-derivatives ofN-acetylneuraminic acid were synthesized and tested for their substrate properties withN-acetylneuraminate lyase fromClostridium perfringens.N-Acetyl-9-deoxyneuraminic acid is a good substrate,N-acetylneuraminic acid derivatives with epimeric configuration at C-7, C-8 or both are cleaved slowly, whileN-acetyl-4-epi-,N-acetyl-4-deoxy-,N-acetyl-7-deoxy-andN-acetyl-8-deoxyneuraminic acid are resistant to enzyme action.N-Acetyl-4-deoxyneuraminic acid andN-acetyl-4-epineuraminic acid competitively inhibit the enzyme. These studies give further insight into a mechanism proposed for the reversible cleavage of sialic acids byN-acetylneuraminate lyase.