Klaus Peseke

Syntheses of branched-chain sugars with push-pull functionality☆

The reaction of methyl 4,6-O-benzylidene-3(2)-deoxy-alpha-D-erythro- hexopyranosid-2(3)-ulose with carbon disulfide, alkyl iodide, and sodium hydride gave methyl 4,6-O-benzylidene-3(2)-[bis(alkylthio)methylene]-3(2)-deoxy-alpha-D- erythro-hexopyranosid-2(3)-uloses. Methyl 4,6-O-benzylidene-2-[bis(methylthio)-methylene]-2-deoxy-alpha-D- erythro-hexopyranosid-3-ulose (5) reacted with aromatic amines to give, in a rearrangement process, N-aryl-2-aryliminomethyl-4,6-O-benzylidene-2-deoxy- alpha-D-erythro-hex-1-enopy-ranosylamin-3-uloses. The reaction of 5 with hydrazine hydrate afforded 5-methylthio-(methyl 4,6-O-benzylidene-2,3-dideoxy-alpha-D-erythro-hexopyranosido)[3,2- c]pyrazole.

An Approach toC-Branched and Heterocyclic Anellated Pyranosides by Reaction ofα-D-erythro-Hexopyranosid-2-ulose with Orthoformic Acid Derivatives

The push-pull functionalization of the ulose 1 to give the (E)-configurated dimethylaminomethylene pyranosidulose 2 was achieved with bis(dimethylamino)tert-butoxymethane. Substitution of the dimethylamino group by different amines provided the corresponding sugar enamines 3 as (Z) isomers. 2 reacted with hydrazine hydrate to furnish the pyrano[3,4-c]pyrazole 4. Treatment of 2 with acetamidine hydrochloride, benzamidine hydrochloride, S-methylisothiouronium methylsulfate and guanidine carbonate, respectively, in the presence of bases yielded the pyrimidoanellated pyranosides 5. Reaction of 2, ethyl 2-cyano-acetimidate hydrochloride 7 and sodium hydride afforded a mixture of a pyrido- and pyranoanellated pyranoside 9 and 10, respectively.

Synthesis of New Pyrazole and Pyrimidine Steroidal Derivatives

The synthesis of steroidal heterocycles containing the pyrazole and pyrimidine ring fused to the 16,17-position of the steroid nucleus is reported. Androstenolone acetate (1) reacted with carbon disulfide, iodomethane and sodium hydride to furnish 3β-acetoxy-16-[bis(methylthio)methylene]-5-androst-5-en-17-one (2). The reactions of 2 with hydrazine hydrate and methylhydrazine afforded the 5’-methylthio- pyrazolo[4’,3’:16,17]androst-5-en-3β-ols 3a and 3b, respectively. Treatment of 2 with amidinium, guanidinium, and isothiuronium salts in the presence of sodium methoxide yielded the 6’-methoxy- pyrimido[5’,4’:16,17]androst-5-en-3β-ols (4a-4e).

Synthesis of Push-Pull Derivatives of Levoglucosenone as Precursors of Annellated Pyranosides

ABSTRACT 1,6-Anhydro-3-deoxy-4-S-ethyl-4-thio-β-D-erythro-hexopyranos-2-ulose (2) reacted with carbon disulphide and iodomethane to furnish 1,6-anhydro-3-[bis(methylthio)methylene]-3-deoxy-4-S-ethyl-4-thio-β-D-erythro-hexopyranos-2-ulose (3). Treatment of 2 with dimethylformamide dimethyl acetal yielded 1,6-anhydro-3-deoxy-3-(dimethylaminomethylene)-4-S-ethyl-4-thio-β-D-erythro-hexopyranos-2-ulose (4). The reactions of 3 with malononitrile and hydrazine hydrate furnished 1,6-anhydro-3-[bis-(methylthio)methylene]-2-(dicyanomethylene)-2,3-dideoxy-4-S-ethyl-4-thio-β-D-erythro-hexopyranose (7) and (1R,7R,8R)-2,3,5,6(2,4,5,6)-tetradehydro-7-ethylthio-5-methylthio-3,4-diaza-10,11-dioxatricyclo[6.2.1.02,6]undecane (8a,b), respectively.

Syntheses of higher sugars by a new chain-elongation reaction

Abstract The reaction of methyl 2,3,4-tri- O -acetyl-6-deoxy-6-nitro-α- d -glucopyranoside and 3,4,5,7-tetra- O -acetyl-2,6-anhydro-1-deoxy-1-nitro- d - glycero - l - manno -heptitol with carbon disulfide, methyl iodide, and sodium hydride gave methyl 2,3,4-di- O -acetyl-6,7-dideoxy-7,7-bis(methylthio)-6-nitro-α- d - gluco -hept-6-enopyranoside ( 3 ) and 4,5,6,8-tetra- O -acetyl-3,7-anhydro-2-deoxy-2-nitro- d - glycero - l - manno -oct-1-enose dimethyl dithioacetal, respectively. Substitution reactions of 3 were investigated.

SYNTHESIS OF (2,3,4,6-TETRA-O-ACETYL-α-D-GLYCOPYRANOSYL) THIOPHENE DERIVATIVES AS NEW C-NUCLEOSIDE ANALOGUES[1]

Treatment of 2-(2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl)ethanal (1a) and 2-(2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl)ethanal (1b) respectively with malononitrile in the presence of silica gel provided the corresponding 4-[2,3,4,6-tetra-O-acetyl-α-D-glycopyranosyl]-2-cyanocrotononitriles (2a) and (2b). Starting from 2a and 2b, respectively, cyclizations with sulfur and triethylamine yielded 5-[2,3,4,6-tetra-O-acetyl-α-D-glycopyranosyl]-2-aminothiophene-3-carbonitriles (3a) and (3b). Further cyclizations could be achieved by utilizing of triethyl orthoformate/ammonia to furnish the 6-(α-D-glycopyranosyl)thieno[2,3-d]pyrimidine-4-amines 4a and 4b.

SYNTHESIS OF ANELLATED PYRANOSE DERIVATIVES ON THE BASIS OF LEVOGLUCOSENONE

ABSTRACT 1,6-Anhydro-2-(dicyanomethylene)-2,3-dideoxy-4-S-ethyl-4-thio-β-D-erythro-hexopyranose (1) reacted with tosyl azide or sulfur and triethylamine to furnish the 5-aza-10, 11-dioxatricyclo[6.2.1.02,6]undeca-2(6),3-diene-3-carbonitrile 2 and the 10,11-dioxa-5-thiatricyclo[6.2.1.02,6]undeca-2(6),3-diene-3-carbonitrile 3, respectively. The reactions of 1 with arylisothiocyanates furnished the 11,12-dioxa-5-thiatricyclo[7.2.1.02,7]dodeca-2(7),3-diene-3-carbonitriles 4 and 5. 3 underwent cyclization with triethyl orthoformate and ammonia or hydrazine hydrate to afford the 5,7-diaza-14,15-dioxa-9-thiatetracyclo[10.2.1.02,10.03.8]pentadecatetra(tri)enes 7 and 8, respectively.

Branched-Chain Sugars as Push-Pull Butadienes

Abstract Treatment of methyl 4,6-O-benzylidene-2-(dicyanomethylene)-2,3-dideoxy-α-D-erythro-hexopyranoside (2) with 3-benzyl-2-methylthio-2-thiazolinium iodide (3), 4,5-dihydro-3-methyl-2-methylthio-1,3-thiazinium iodide (5) and 3-benzyl-4,5-dihydro-2-methylthio-1,3-thiazinium iodide (6), respectively, gave methyl 4,6-O-benzylidene-3-[(2Z)-3-benzyl-2-thiazolidinylidene, 3-methyl-1,3-thiazinan-2-ylidene and 3-benzyl-1,3-thiazinan-2-ylidene]-2-(dicyanomethylene)-2,3-dideoxy-α-D-erythro-hexopyranoside (4), (7), (8), respectively.

Synthesis of Novel Anellated Pyranosides as Precursors of C‐Nucleoside Analogues Using Isopropyl 6‐O‐Acetyl‐3‐deoxy‐4‐S‐ethyl‐4‐thio‐α‐D‐threo‐hexopyranosid‐2‐ulose

Abstract Isopropyl 6‐O‐acetyl‐3‐deoxy‐4‐S‐ethyl‐4‐thio‐α‐D‐threo‐hexopyranosid‐2‐ulose (3) was converted to the corresponding 3‐[bis(methylthio)methylene] derivative 4 with a push–pull activated C–C double bond. Treatment of 4 with hydrazine and methylhydrazine afforded the pyrano[3,4‐c]pyrazol‐5‐ylmethyl acetates 5a and 5b, respectively. Desulfurization of compound 4 with sodium boron hydride yielded the 3‐[(methylthio)methylene]hexopyranosid‐2‐ulose 7. Compound 7 was reacted with amines to furnish 3‐aminomethylene‐hexopyranosid‐2‐uloses 8, 9. Reaction of 7 with hydrazine hydrate, hydrazines, hydroxylamine, and benzamidine afforded the pyrazolo, isoxazalo, and pyrimido anellated pyranosides (10–13). #Dedicated to Professor Dr. Günther Oehme on the occasion of his 65th birthday.

SYNTHESIS OF PRECURSORS FOR NEW PYRIMIDINE ACYCLO-C-NUCLEOSIDE ANALOGUES BY RING TRANSFORMATION OF 2-FORMYLGALACTAL 1-2 *,†

Reactions of 2-formylgalactal 1, presented as an unsaturated sugar derivative with push-pull functionalization, with guanidinium and amidinium salts, respectively, were carried out under basic conditions to furnish the substituted 5-(1,2,4-tri-O-benzyl-d-lyxo-1,2,3,4-tetrahydroxybutyl)pyrimidines 2–4. Treatment of 1 with 2-aminobenzimidazole and 3-amino-1,2,4-triazole, respectively, afforded 3-(1,2,4-tri-O-benzyl-d-lyxo-1,2,3,4-tetrahydroxybutyl)benzo[4,5]imidazo[1,2-a]pyrimidine (5) and 6-(1,2,4-tri-O-benzyl-d-lyxo-1,2,3,4-tetrahydroxybutyl)-[1,2,4]triazolo[1,5-a]pyrimidine (6). *Dedicated to Professor Dr. Dr. hc. Frieder W. Lichtenthaler on the occasion of his 70th birthday. †Presented at the XXth International Carbohydrate Symposium, Hamburg, Germany, 2000.