Saburo Inokawa

Sugar Analogs Having Phosphorus in the Hemiacetal Ring

Publisher Summary This chapter provides an overview of sugar analogs having phosphorus in the hemiacetal ring. There exist many naturally occurring sugars in which a hydroxyl group of a monosaccharide is replaced by an amino or a thiol group. These compounds, commonly called “amino” or “thio sugars,” play a wide variety of important biological roles. Representative examples of these classes are 2-acetamido-2-deoxy-α- d -glucose and 7-(5-S-methyl-5-thio-β- d -ribosyl) adenine (vitamin L2). The former is the product of hydrolysis of chitin and occurs in various mammalian polysaccharides and in certain proteins, whereas the latter is known to be a factor necessary for lactation. No analogous sugars having phosphorus attached to a ring-carbon atom appear to occur in Nature, although numerous sugar phosphates and some compounds containing a C–P bond are known. This chapter draws attention towards the chemistry and biochemistry of sugar analogs having phosphorus in the ring. It discusses the most thoroughly investigated substances—that is, those having a pyranoid ring and the substances with a furanoid ring.

Synthesis of 1,2,4-tri-O-acetyl-3,6-di-O-benzyl-5-deoxy-5-C-[(S)-phenylphosphinyl]-β-d-glucopyranose: The first gluco type of hexopyranose derivative having phosphorus in the hemiacetal ring

Abstract Oxidation of 3,6-di- O -benzyl-1,2- O -isopropylidene-α- d -glucofuranose with pyridinium chlorochromate in the presence of molecular sieves, followed by conversion into the p -tolylsulfonylhydrazone, addition of methyl phenylphosphinate, and reduction with sodium borohydride, provided the key intermediate, namely, 5( R , S )-3,6-di- O -benzyl-5-deoxy-1,2- O -isopropylidene-5- C -[(methoxy)phenylphosphinyl]-α- d - xylo -hexofuranose, in 23% overall yield. Treatment of this compound with sodium dihydrobis(2-methoxyethoxy)aluminate, followed by the action of mineral acid and acetic anhydride, yielded the crystalline title compound, the structure of which was established on the basis of mass and 400-MHz, 1 H-n.m.r. spectra. A general dependence of 2 J PH values on the OPCH dihedral angles effectively served for assigning the configuration of C-1, C-5, and the ring-phosphorus atom of the present product and other such 5- C -phosphinylhexopyranoses.

Synthesis of 4,5-dideoxy-4-C-[(R,S)-phenylphosphinyl]-d-ribo- and l-lyxo-furanose and their 1,2,3-triacetates

Abstract 2,3- O -Isopropylidene- d -ribose diethyl dithioacetal, prepared from d -ribose, was converted in three steps into the corresponding dimethyl acetal, which was monotosylated at O-5, and the ester oxidized at C-4 with pyridinium chlorochromate; addition of methyl phenylphosphinate to the resulting pentos-4-ulose derivative then provided (4 R,S )-4,5-anhydro-2,3- O -isopropylidene-4- C -[( R,S )-(methoxy)phenylphosphinyl]- d - erythro -pentose dimethyl acetal. Hydrogenation of this compound in the presence of Raney Ni, followed by reduction with SDMA, hydrolysis, and acetylation, yielded the title compounds (seven kinds), the structures of which were established on the basis of their 400-MHz, 1 H-n.m.r. and mass spectra. A general dependence of the 2 J PH and 3 J PH values on the OPCH and PCCH dihedral angles provided an effective method for the assignment of the configurations and conformations of these 4-deoxy-4-phosphinyl-pentofuranoses.

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.

Synthesis, and x-ray structural analysis, of 1,2,3,4-tetra-O-acetyl-5,6-dideoxy-5-C-[(S)-phenylphosphinyl]-α- and -β-l-idopyranose

Abstract The title compounds and two diastereoisomers were prepared from (5 RS )-3- O -benzyl-5,6-dideoxy-5- C -[( RS )-(ethoxy)phenylphosphinyl]-1,2- O -isopropylidene-α- d - xylo -hexofuranoses upon reduction with sodium dihydrobis(2-methoxyethoxy)-aluminate, followed by hydrolysis with mineral acid, and acetylation with acetic anhydride-pyridine. Among these products, the two readily crystallized compounds were determined by X-ray crystallographic analysis to be 1,2,3,4-tetra- O -acetyl-5,6-dideoxy-5- C -[( S )-phenylphosphinyl]-α- and -β- l -idopyranose- 4 C 1 .

X-ray crystal, and molecular, structure of 1,2,3,4-tetra-O-acetyl-5,6-dideoxy-6-C-nitro-5-(phenylphosphinyl)-l-ido-pyranose: a correction of our previous work thereon

Abstract X-ray crystallographic analysis was performed on the compound to which had been assigned the structure of 1,2,3,4-tetra- O -acetyl-5,6-dideoxy-6- C -nitro-5-(phenylphosphinyl)- d -glucopyranose. The results showed that the compound has the l - ido configuration, the pyranoid ring is in the 4 C 1 ( l ) conformation, the acetoxyl groups at C-1 and C-5 and the phenyl ring on P are linked axially, and the acetoxyl groups at C-2, C-3, and C-4 are linked equatorially.

X-Ray crystal and molecular structure of 1,2,3,5-tetra-O-acetyl-4-deoxy-4-C-[(S)-ethylphosphinyl]-α-d-ribofuranose, and conformations of aldopentofuranose analogs having phosphorus in the hemiacetal ring

Abstract X-Ray crystallographic analysis was performed on the compound to which had been assigned the structure 1,2,3,5-tetra- O -acetyl-4-deoxy-4- C -[( S )-ethylphosphinyl]-α- d -ribofuranose. The results showed that the compound has the proposed configuration, the five-membered ring is in the 3 T 2 conformation with a tendency towards the E 2 form, the substituents on C-1, C-4, and P-5 are linked bisectionally, and the acetoxyl groups on C-2 and C-3 are respectively attached axially and equatorially. Based on the X-ray crystallographic and 1 H-n.m.r.-spectral data, favored conformations of P-in-ring analogs of aldopentofuranose peracetates in solution are discussed.

Formation and X-ray structural analysis of 2,3,4-tri-O-acetyl-1,5-anhydro-5,6-dideoxy-5-C-[(S)-phenylphosphinyl]-l-iditol: A further mechanistic study of the ring enlargement of (5RS)-5-deoxy-5-C-[(RS)-phosphinyl]-α-d-xylo-hexofuranoses to give 5-deoxy-5-C-[(RS)-phosphinyl]-α,β-l-idopyranoses

Abstract The minor byproduct formed during the ring enlargement of (5RS)-5,6-dideoxy-5-C-[(RS)-(ethoxy)phenylphosphinyl]-1,2-O-isopropylidene-α- d -xylo-hexofuranoses to 5,6-dideoxy-5-C-[(RS)-phenylphosphinyl]-α,β- l -idopyranose was determined by X-ray crystallographic analysis to be 2,3,4-tri-O-acetyl-1,5-anhydro-5,6-dideoxy-5-C-[(S)-phenylphosphinyl]- l -iditol-4C1. This unique, ring enlargement was closely examined, and a possible pathway for the formation of these 5-deoxy-5-phosphinyl- l -ido derivatives is discussed.

Addition reactions of glycosid-4-uloses and related compounds with some phosphorus compounds

Abstract Methyl 6-deoxy-2,3-O-isopropylidene-α- l -lyxo-hexopyranosid-4-ulose (2) was treated with methyl phenylphosphinate in the presence of triethylamine, to give mainly methyl 6-deoxy-2,3-O-isopropylidene-4-C-[(methoxy)phenylphosphinyl]-α- l -talopyranoside. Treatment of compound 2 with dimethyl and diethyl phosphonate under the same reaction conditions also afforded adducts having the l -talo configuration. The reaction of (6-S)-tetrahydro-6-methoxypyran-3-one with dimethyl phosphonate and methyl phenylphosphinate, respectively, gave the corresponding adducts in good yields. The reaction of methyl 2,3-O-isopropylidene-α,β- l -erythro-pentopyranosid-4-ulose and 2,3,5-tri-O-benzyl-aldehydo- l -threo-pentos-4-ulose 1-(dimethyl acetal) with methyl and phenyl phenylphosphinate also gave the corresponding adducts. These results suggest that the substituents on the sugar skeleton play an important role in the addition of phosphorus compounds.

X-ray crystal, and molecular, structure of 1,2,3-tri-O-acetyl-4,5-dideoxy-4-C-[(R)-phenylphosphinyl]-α-l-lyxofuranose: The first x-ray analysis of a pentofuranose having phosphorus in the hemiacetal ring

Abstract X-Ray crystallographic analysis was performed on the compound to which had been assigned the structure of 1,2,3-tri- O -acetyl-4,5-dideoxy-4- C -[( R )-phenylphosphinyl]-α- l -lyxofuranose. The results showed that the compound has the proposed configuration, the five-membered ring is in the E 3 conformation, with a tendency towards the 3 T 2 form, the substituents at P-5 and C-5 are linked bisectionally, the acetoxyl group at C-2 and the methyl group at C-4 are linked quasiequatorially, and the acetoxyl group at C-3 is linked axially.