Tadashi Hanaya

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.

An improved synthesis of the 5-deoxy-5-(hydroxyphosphinyl)- d-glucopyranoses, and crystal structures of 1,2,3,4,6-penta-O-acetyl-5-deoxy-5-[(R)-methoxyphosphinyl]- β-d-glucopyranose and its 5-[(R)-ethylphosphinyl] congener

Abstract Treatment of 3- O -acetyl-5-deoxy-5-(dimethoxyphosphinyl)-1,2- O -isopropylidene- α- d -glucofuranose ( 7 ) with dihydropyran in the presence of pyridinium p -toluenesulfonate gave the 6- O -(tetrahydropyran-2-yl) derivative in 91% yield. Ring-enlargement of this compound by the known, 2-step procedure gave 5-deoxy- 5-(hydroxyphosphinyl)- d -glucopyranoses in an overall yield from 7 twice as high as that obtained by the previous, alternative route via the corresponding 6- O -(triphenylmethyl)- α- d -glucofuranose precursor. X-Ray crystallographic analyses were performed on the two title compounds, penta- O -acetyl-5-deoxy-5-(methoxyphosphinyl)- ( 12b ) and -5-(ethylphosphinyl)-β- d -glucopyranose ( 13b ). The results show that both have the 4 C 1 conformation and the substituents on C-1 to C-5 are quasi-equatorial (nomenclature of Jeffrey and Yates). The methoxy group of 12b is in a quasi-equatorial position, whereas the ethyl group of 13b is attached bisectionally to P-5.

An Efficient Synthetic Route for a Versatile Ciliapterin Derivative and the First Ciliapterin D-Mannoside Synthesis

The key precursor, N(2)-(N,N-dimethylaminomethylene)-1’-O-(4-methoxybenzyl)-3-[2-(4-nitrophenyl)ethyl]ciliapterin (15) was efficiently prepared from D-xylose via an improved route. The first synthesis of 2’-O-(α-D-mannopyranosyl)ciliapterin (2c) was achieved by treatment of 15 with 2,3,4,6-tetra-O-benzoyl-α-D-mannnopyranosyl bromide in the presence of silver triflate and tetramethylurea, followed by removal of the protecting groups.

Stereoselectivity in deoxygenation of 5-hydroxy-5-phosphinyl-hexofuranoses (α-hydroxyphosphonates)

The addition of dimethyl phosphonate to six different hexofuranos-5-uloses in the presence of DBU, followed by esterification with methoxalyl chloride and then radical reduction, afforded 5-deoxy-5-dimethoxyphosphinyl-D- and L-hexofuranoses. The stereoselectivity of the deoxygenation and possible transition-state models are discussed.

Formation and characterization of 5-C-[(R)-(1-acetoxy-ethenyl)phosphinyl]-1,2,4-tri-O-acetyl-5-deoxy-3-O-methyl-β-d-xylopyranose

Abstract Treatment of 5-deoxy-3- O -methyl-5- C -phosphinyl- d -xylopyranose with acetic anhydride in pyridine gave, along with other products, a peracetylated derivative, to which the title structure was assigned on the basis of 400-MHz, 1 H-n.m.r. and high-resolution mass spectra. The previous, 5- C -[( S )-(1-acetoxyethenyl)phosphino] structure, presented for the by-product during the preparation of tri- O -acetyl-5-deoxy-5- C -(methoxyphosphinyl)-3- O -methyl- d - xylopyranoses, is now replaced by the new formulation. Possible structures of other products of the acetylation are discussed. Analysis of the mass spectrum of a sugar analog having a 5-deoxy-5- C -(phosphinyl)- d -xylopyranose ring-system is made.

A new route for preparation of 5-deoxy-5-(hydroxyphosphinyl)-D-mannopyranose and -L-gulopyranose derivatives

Starting from methyl 2,3-O-isopropylidene-α-D-mannofuranoside (5), methyl 6-O-benzyl-2,3-O-isopropylidene-α-D-lyxo-hexofuranosid-5-ulose (12) was prepared in three steps. The addition reaction of dimethyl phosphonate to 12, followed by deoxygenation of 5-OH group, provided the 5-deoxy-5-dimethoxyphosphinyl-α-D-mannofuranoside derivative 15a and the β-L-gulofuranoside isomer 15b. Reduction of 15a and 15b with sodium dihydrobis(2-methoxyethoxy)aluminate, followed by the action of HCl and then H2O2, afforded the D-mannopyranose (17) and L-gulopyranose analog 21, each having a phosphinyl group in the hemiacetal ring. These were converted to the corresponding 1,2,3,4,6-penta-O-acetyl-5-methoxyphosphinyl derivatives 19 and 23, respectively, structures and conformations (4C1 or 1C4, resp.) of which were established by 1H-NMR spectroscopy.

Synthesis of 5-deoxy-5-hydroxyphosphinyl-D-mannopyranoses

The title sugar analogues (13) were synthesized by starting with known methyl (E)-5,6-dideoxy-2,3-O-isopropylidene-6-nitro-α-D-lyxo-hex-5-enofuranoside (5a) in six steps through the key intermediate, methyl 5-deoxy-5-dimethoxyphosphinyl-2,3-O-isopropylidene-α-D-mannofuranoside (8a). The products (13) were converted into the corresponding penta-O-acetyl-5-methoxyphosphinyl derivatives (14), whose structures and conformations (mostly 4 C 1 ) were established by spectroscopy

Synthesis of 6-Hydroxymethylpterin α- and β-D-Glucosides

The key precursor, N(2)-(N,N-dimethylaminomethylene)-6-hydroxymethyl-3-[2-(4-nitrophenyl)ethyl]pterin (11) was efficiently prepared from 2,5,6-triamino-4-hydroxypyrimidine (8) in 5 steps. The first, unequivocal synthesis of 6-hydroxymethylpterin α-D-glucoside (6a) was achieved by treatment of 11 with 4,6-di-O-acetyl-2,3-di-O-(4-methoxybenzyl)-α-D-glucopyranosyl bromide (16) in the presence of tetraethylammonium bromide and N-ethyldiisopropylamine, followed by removal of the protecting groups, while 6-hydroxymethylpterin β-D-glucoside (6b) was prepared by means of selective glycosylation of 11 with 2,3,4,6-tetra-O-benzoyl-α-D-glucopyranosyl bromide (12) in the presence of silver triflate and tetramethylurea.

Novel efficient synthesis and structural analysis of furanose-type phosphono sugars

Reaction of 2-benzyloxymethyl-1-methoxy-3-phospholene 1-oxide with mCPBA afforded 3,4-epoxyphospholane derivatives, whose isomerized allylic alcohols were cis-dihydroxylated by osmium(VIII) oxide-catalyzed oxidation to give ribo-, arabino-, xylo-, and lyxofuranose-type phosphono sugars. The nmr data suggest a twist conformation

Synthesis of phospholane 1-oxide having oxygen functional groups from a 4-bromobutylphoshinate derivative

Ethyl 4-bromo-2,3-dimethoxybutyl(phenyl)phosphinate (10a) was prepared from 2,3-di-O-methyl-L-threitol (12) in five steps. Reduction of 10a with sodium dihydrobis(2-methoxyethoxy)aluminate, followed by the action of hydrogen peroxide, afforded 3,4-dimethoxy-l-phenylphospholane 1-oxide (3), while the reaction of 10a with magnesium in boiling THF resulted in the formation of ethyl 2-methoxy-3-butenyl(phenyl)phosphinate (26).