Kuniaki Seo

Synthesis of a 6-c-nitro-d-glucopyranose derivative having phosphorus in the hemiacetal ring

Abstract 5,6-Dideoxy-6-C-nitro-5-(phenylphosphino)- d -glucopyranose was prepared by addition of phenylphosphine to 3-O-acetyl-5,6-dideoxy-1,2-O-isopropylidene-6-C-nitro-α- d -xylo-hex-5-enofuranose, followed by hydrolysis of the resulting 3-O-acetyl-5,6-dideoxy-1,2-O-isopropylidene-6-C-nitro-5-(phenylphosphino)- d -glucofuranose (10). Acetylation of 10 gave the crystalline 1,2,3,4-tetraacetate (16). 5,6-Dideoxy-6-C-nitro-5-(phenylphosphinyl)- d -glucopyranose (15) was obtained by oxidation of 10, and hydrolysis of the resulting 5-phenylphosphinyl compound. Acetylation of 15 gave the 1,2,3,4-tetraacetate (17). Although the n.m.r. spectrum of 17 was complex, the n.m.r. spectrum of 16 was rather simple. The n.m.r. data showed that 16 is the α anomer in the 4C1( d ) conformation.

A new route for formation of the carbon-phosphorus bond, and synthesis of 1,2,4-tri-O-acetyl-5-deoxy-3-O-methyl-5-C-[(R)- and (S)-phenylphosphinyl]-α- and -β-d-xylopyranose

Abstract Deoxygenation at the carbon atom α to the phosphorus atom of 1,2- O -isopropylidene-5- C -(methoxyphenylphosphinyl)-3- O -methyl-α- d -xylofuranose ( 7 ), prepared from 1,2- O -isopropylidene-3- O -methyl-α- d - xylo -pentodialdo-1,4-furanose by reaction with methyl phenylphosphinate, was performed by successively treating 7 with 1,1′-(thiocarbonyl)diimidazole (TCDI) and tributyltin hydride. Treatment of the resulting 5-deoxy-1,2- O -isopropylidene-5- C -(methoxyphenylphosphinyl)-3- O -methyl-α- d -xylofuranose with sodium dihydrobis(2-methoxyethoxy)aluminate, followed by mineral acid, and then acetic anhydride in pyridine, gave the four title compounds, which were separated by column chromatography on silica gel and recrystallization, and characterized by 1 H-n.m.r.-spectral analysis and their optical rotations.

Synthesis of 1,2,4-tri-O-acetyl-5-deoxy-5-C-[(R and S)-methoxy-phosphinyl]-3-O-methyl-α- and -β-d-xylopyranose, and their structural analysis by 400-MHz, proton nuclear magnetic resonance spectroscopy

Abstract 5-Deoxy-5-iodo-1,2- O -isopropylidene-3- O -methyl-α- d -xylofuranose, prepared quantitatively from its 5- O p -tolylsulfonyl precursor, readily gave the 5- C -(diethoxy-phosphinyl) derivative. Treatment of this compound with sodium dihydrobis(2-methoxyethoxy)aluminate, followed by hydrogen peroxide, mineral acid, and hydrogen peroxide, yielded 5-deoxy-5- C -(hydroxyphosphinyl)-3- O -methyl-α,β- d -xylopyranoses in 65% overall yield. The structures of these sugar analogs were effectively established on the basis of the mass and 400-MHz, 1 H-n.m.r. spectra of the four title compounds, derived by treatment with diazomethane and then acetic anhydride in pyridine. 5- C -[( S )-(1-Acetoxyethenyl)phosphino]-1,2,4-tri- O -acetyl-5-deoxy-3- O -methyl-β- d -xylopyranose was also isolated and characterized.

Sugars containing a carbon-phosphorus bond : Part V. 5-deoxy-5-(ethylphosphinyl)-D-ribopyranose

Abstract The Michaelis-Arbuzov reaction of methyl 5-deoxy-5-iodo-2,3- O -isopropylidene-β- D -ribofuranoside ( 4 ) with diethyl ethylphosphonite gave methyl 5-deoxy-5-(ethoxyethylphosphinyl)-2,3- O -isopropylidene-β- D -ribofuranoside ( 5 ) which, on treatment with sodium dihydrobis(2-methoxyethoxy)aluminate, afforded methyl-5-deoxy-5-(ethylphosphinyl)-2,3- O -isopropylidene-β- D -ribofuranoside ( 9 ). Hydrolysis of 9 with hydrochloric acid yielded a mixture of the anomeric 5-deoxy-5-(ethylphosphinyl)- D -ribopyranoses ( 10 ). The hygroscopic, syrupy mixture 10 was converted into a syrup consisting of the two 1,2,3,4-tetra- O -acetyl-5-deoxy-5-(ethylphosphinyl)- D -ribopyranoses ( 11 ).

Preparation of Novel Cyclophosphamides Derivatives of Sugars

Novel cyclophosphamide derivatives bearing a sugar structure were prepared by the treatment of the amino sugars from D-glucose and D-xylose with bis-(2-chloroethyl)aminophosphoric dichloride as well as with phosphoryl chloride and nucleophiles

Synthesis of 1,2,4-tri-O-acetyl-5-deoxy-3-O-methyl-5-C-[(R)- and -(S)-phenylphosphinyl]-β-d-ribopyranose

Abstract 5-Deoxy-1,2- O -isopropylidene-5- C -(methoxyphenylphosphinyl)-3- O -methyl-α- d -ribofuranose ( 4 ) was prepared from 1,2- O -isopropylidene-3- O -methyl-α- d - ribo -pentodialdo-1,4-furanose by an addition reaction with methyl phenylphosphinate, followed by deoxygenation of the terminal HOCHP group of the adduct by successive reaction with 1,1′-thiocarbonyldiimidazole and tributyltin hydride. Treatment of 4 with sodium dihydrobis(2-methoxyethoxy)aluminate, followed by deacetonation with mineral acid, and acetylation with acetic anhydride—pyridine, gave mainly the two title compounds, which were isolated by column chromatography on silica gel, and characterized by 90-MHz, 1 H-n.m.r.-spectral analysis.

Synthesis of 5-deoxy-3-O-methyl-5-C-(phenylphosphinyl)-l-idopyranose

Synthese a partir de didesoxy-5,6 O-isopropylidene-1,2 O-methyl-3 nitro-6 α-D-xylo-hexeno-5furanose et de phenylphosphine

Synthesis of 1,2,4-tri-O-acetyl-6-deoxy-6-C-(isopropylphosphinyl)-3,5-di-O-methyl-d-glucoseptanose and 1,2,4-tri-O-acetyl-3-O-benzyl-6-C-(butylphosphinyl)-6-deoxy-5-O-methyl-d-glucoseptanose

Abstract The Michaelis—Arbuzov reaction of 6-deoxy-6-iodo-1,2- O -isopropylidene-3- O -methyl-α- d -glucofuranose with diethyl isopropylphosphonite afforded 6-deoxy-6- C -(ethoxyisopropylphosphinyl)-1,2- O -isopropylidene-3- O -methyl-α- d -glucofuranose ( 3 ). Similarly, using 3- O -benzyl-6-deoxy-6-iodo-1,2- O -isopropylidene-α- d -glucofuranose and diethyl butylphosphonite, 3- O -benzyl-6-deoxy-6- C -(ethoxybutylphosphinyl)-1,2- O -isopropylidene-α- d -glucofuranose ( 4 ) was obtained. Treatment of 3 and 4 with methyl iodide—silver oxide afforded the corresponding 5- O -methyl compounds, 5 and 6 , respectively. Treatment of 5 with sodium dihydrobis(2-methoxyethoxy)aluminate, followed by mineral acid, and then acetic anhydride in pyridine, gave the two isomers of 1,2,4-tri- O -acetyl-6-deoxy-6- C -(isopropylphosphinyl)-3,5-di- O -methyl- d -glucoseptanose and a mixture of 1,2-di- O -acetyl-6-deoxy-6- C -(isopropylphosphinyl)-3,5-di- O -methyl-α- and -β- d -glucofuranose, which were separated by column chromatography on silica gel. Similarly, from 6 , the two isomers of 1,2,4-tri- O -acetyl-3- O -benzyl-6- C -(butylphosphinyl)-6-deoxy-5- O -methyl- d -glucoseptanose and a mixture of 1,2-di- O -acetyl-3- O -benzyl-6- C -(butylphosphinyl)-6-deoxy-5- O -methyl-α- and -β- d -glucofuranose were obtained.

Synthesis and structural analyses of 3-acetamido-1,4-di-O-acetyl-2,3,5-trideoxy-5-C-(isopropylphosphinyl)-D- erythro-pentopyranoses

1H NMR spectroscopy of phosphorus containing hetero sugars (phospha sugars), revealed the alpha and beta configurations and chair conformations for 3-acetamido-1,4-di-O-acetyl-2,3,5-trideoxy-5-C-(isopropylphosphinyl)-alpha- and beta-D-erythro-pentopyranoses. The conformation of the title compounds was determined by 1H NMR as 1C4 in CDCl3 and the conformation was in accord with that in solid state determined by X-ray crystallographic analysis.

Optically active diazacyclophosphamides: novel efficient reagents for the determination of the absolute configuration of amines and alcohols

Various amines and alcohols are converted into the corresponding phosphamides by the action of optically active diazacyclophosphamidic chlorides and absolute configurations of amines and alcohols are readily determined by proton and phosphorus NMR of the cyclophosphamides that are formed.