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The synthesis and antitumor activity evaluation of new branched phospha sugars, especially deoxybromophospha sugar derivatives or bromophospholanes of 2,3-dibromo-3-methyl-1-phenylphospholane 1-oxide (DBMPP: 3) and 2,3,4-tribromo-3-methyl-1- phenylphospholane 1-oxide (TBMPP: 4), against various types of leukemia cell lines as well as the results of the mechanistic studies for characterizing and developing the novel multiple type molecular targeted antitumor agents are reported in this paper. DBMPP and TBMPP were prepared from 1-phenyl-3-methyl-2-phospholene 1-oxide (1). The isomer mixture of phospha sugars prepared were evaluated as novel antitumor agents by MTT in vitro method. DBMPP and TBMPP were characterized by flow cytometry and Western blot analysis and were revealed to be potential antitumor agents against leukemia cell lines of K562 (one type of leukemia cell lines of CML) and U937 (one type of leukemia cell lines of AML) as well as against the various types of leukemia cell lines and al...

Starting materials of phosphasugars, 1-phenyl-2-phospholene 1-oxides, were prepared from dienes and phenylphosphonous dichloride (dichlorophenylphosphine). Several substituted novel phosphasugars (3- or 4-halo-substituted)-1-phenyl-2-phospholene 1-oxides as well as 1-phenyl-2-phospholane 1-oxides were prepared from 2-phospholenes. The synthesized compounds were evaluated for their antitumor activities against the leukemia cell lines (U937 and K562) by in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. 2,3,4-Tribromo-3-methyl-1-phenylphospholane 1-oxide showed superior antitumor activity against U937 and K562 cell lines in a comparative evaluation with Glivec. The analysis by flow cytometry implied that 2,3-dibromo-3-methyl-1-phenylphospholane 1-oxide induced apoptosis to leukemia cell lines.

Novel Sugar Dendritic Gd(III)-DTPA complexes for MRI Contrast Agents (CAs) were prepared and evaluated by in vitro and in vivo methods. The sugar dendritic MRI contrast agents had a good blood vessel pool character and drew blood vessels and liver cancers remarkably clearer and longer time enough than the clinically being used Gd(III)-DTPA complex (Magnevist). Phospha sugar derivatives or phosphorus heterocyclic derivatives provided by functional groups such as epoxide, bromide, etc., were prepared and evaluated by the MTT in vitro method. These phospha sugar derivatives showed excellent anti-proliferative effects of leukemia cell lines, e.g., K562 and U937, as well as solid cancer cells in fashions of (i) higher activity, (ii) wider spectra, and (iii) higher selectivity and specificity than Imatinib mesylate (Gleevec), which is one of the most frequently used chemotherapeutical molecular targeting anti-tumour agent.

Phospha sugars were prepared by a novel synthetic route starting from phosphorus heterocyclic compounds, 2-phospholenes. The anhydro- and deoxy-phospha sugar derivatives have been revealed to have potential anticancer activities against human leukemia of K562 and U937 cell lines. In this article, deoxybromophospha sugars with different numbers of bromo substituents were prepared, and their anticancer activities were evaluated by MTT method. The order of the activities depending on the number of bromo substituent was first revealed, and trideoxytribromotetrofuranose type phospha sugar [2,3,4-tribromo-3-methyl-1-phenylphospholane 1-oxide (4: TBMPPAO)] was the most active among these phospha sugars prepared. Diasteromers of dideoxydibromotetrofuranose-type phospha sugar [2,3-dibromo-3-methyl-1-phenylphospholane 1-oxide (2: DBMPPAO)] were separated into four components, and the structure as well as the character of each component was assigned by spectral and chromatographic data as well as by MTT met...

The synthesis of new phospha sugar analogues or phosphorus heterocycles and their biological activities as novel anticancer agents are reported in this article. A 1,2-dibromo-1,2-dideoxy phospha sugar derivative, 2,3-dibromo-3-methyl-1-phenylphospholane 1-oxide (2), was prepared from 1-phenyl-3-methyl-2-phospholene 1-oxide (1), and the yield and ratio of diastereomers 2a to 2d were changed by a catalyst such as manganese(IV) oxide and manganese(II) bromide. The antitumor activities of the mixture of dibromides 2 and the separated diastereomeric components 2a to 2d of the dibromides were evaluated by MTT in vitro method against the human leukemia cell lines of K562 and U937. The results showed that all of the diastereomers 2a to 2d as well as the diastereomer mixture exert excellent anticancer activity, and moreover, among them, diastereomer 2d showed the highest antitumor activity. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silico...

Construction of light-harvesting reverse micelle system was achieved in nanoscopic dimensions via self-assembly of anthracene–perylene triad which could undergo efficient intramolecular energy transfer from the anthracene antennae to the perylene cores. Absorption spectra of the reverse micelles in toluene solutions exhibited broad, unstructured, and red-shifted bands attributed to interacting chromophores within molecular aggregates, while the emission spectra showed significant fluorescence quenching of both the excited anthracene and the perylene groups. The atomic force microscope (AFM) analysis revealed a number of small and medium-sized spherical objects that can be attributed to the individual reverse micelles and their assemblies. A cross-sectional view of the AFM image indicated that nearly 90% of these peak heights were less than 10 nm. Titration experiments of fluorescence properties of the reverse micelles allowed determination of its cmc value as 3 μM. Spectroscopic and microscopic behavior of a series of the reverse micelles at the W 0 values (water/surfactant ratios) of 30, 50, 100, and 200 suggested that the reverse micelles should have a uniform aggregate size independent of the water/surfactant ratio, revealing a unique relation between specific geometrical configuration of the amphiphilic molecules and intrinsic size of the reverse micelles.

In the present paper, we report a new approach toward light-harvesting reverse micellar systems from molecular blends of anthracene and perylene building blocks. The self-assembly initiated by protonation of the molecular blends gave rise to the mixed reverse micelles, in which intermolecular energy transfer from the anthracene to the perylene chromophores was observed. The atomic force microscope (AFM) studies on the reverse micelles prepared from the donor and acceptor blends at a range of the feed ratios showed a number of nanoscale-sized spherical objects homogeneously dispersed on the highly oriented pyrolytic graphite (HOPG) substrate. The critical micelle concentration (cmc) values of the reversed micelles at the donor:acceptor ratios of 100:0, 50:50, and 0:100 were estimated to be 7, 3, and 10 μM by fluorescence batch titrations, respectively, indicating that the cmc values should be almost equivalent regardless of the constitution of each chromophoric component. Attempt to generate the mixed reverse micelles through pairwise mixing of the donor- and acceptor-based reverse micelles resulted in spectral behaviors identical with those obtained by the self-assembly employing the donor–acceptor blends. This suggests that these two reverse micelles undergo thermodynamic exchange of the surfactant molecules to afford the mixed reverse micelles when mixing the two discrete reverse micellar systems.

The effect of low-temperature surface-wave plasma treatment with various gases on surface modification of chitosan was investigated using the surface-wave plasma. Chitosan is a nontoxic, biocompatible and biodegradable polymer. It is thought that an increase in amino groups, a key constituent of chitosan molecules, will be useful for biomedical applications, such as improvement of blood clotting properties, drug delivery system, prodrug using derivatization and so on. In this study, therefore, we have focused on the amino group introduction on chitosan surface by using Ar, O 2 , NH 3 and NH 3 –He mixed gas plasmas. The experimental results of X-ray photoelectron spectroscopy measurements showed that N/C atomic ratio increased from 6.8% to 14.7% after NH 3 plasma treatment. With O 2 plasma treatment, the surface roughness of chitosan film was significantly modified from 1.96 nm to 14.6 nm. The blood clotting time of the sample treated by NH 3 and He plasma with O 2 pretreatment was reduced to 55.2% of that of untreated one.

In this article, we report the results of the low-temperature chemical modification of a polyurethane (PU) surface using surface-wave excited N2/H2 plasma. Optical emission spectroscopy (OES) and double-probe measurement were performed to obtain optimum plasma properties. X-ray photoelectron spectroscopy (XPS) was employed to characterize the changes on the PU surface and to estimate the amount of introduced nitrogen-containing groups. The result shows that the largest amount of increase was obtained in the case of 90% N2/(N2 + H2) plasma where the N/C ratio on the PU surface increased from 0.0128 before plasma treatment to 0.131 after plasma treatment.

A new low-molecular weight dendrimer-like MRI contrast agent (Gd-D1) has been synthesized and characterized in vitro by proton and oxygen-17 relaxometry. Its pharmacokinetic parameters and biodistribution patterns were evaluated on rats. Its in vitro and in vivo properties, that is, the longitudinal relaxivity (defined as the increase of the water proton longitudinal relaxation rate induced by one millimole per liter of Gd-D1) equal to 5.6s(-1)mM(-1) at 20 MHz and 310 K, the elimination half-time equal to 85 min, and its low accumulation in liver and spleen, underline its potential as a blood-pool MRI contrast agent.

A series of anthracene-clustering dendrimers bearing various aliphatic substituents at the terminal positions were synthesized using a direct coupling strategy. A remarkable effect of the side chains was imparted to chemical properties of the dendrimers such as drastically increased solubility. Although the multibranched anthracene arrays in the dendritic architectures exhibited no cooperativity in terms of the absorption feature and behaved as single chromophoric systems, investigations focusing on fluorescence properties revealed that a type of cooperativity was present as expressed in the reduced quantum yields of fluorescence. An alternative approach utilizing time-resolved fluorescence decay measurements clearly demonstrated that the most reasonable mechanism of the cooperative action should involve two discernible channels of intramolecular fluorescence resonance energy transfer (FRET) occurring from one chromophore to the others within and across junctions of the branching units.

A novel synthetic approach is described to incorporate one more carbon atom at C-2 position of phospholane oxides as homologated allylic alcohol by treatment of erythro -2,3-epoxy-3-methylphospholane 1-oxides with excess of dimethylsulfonium methylide.

Several new classes of deoxy phospha sugar derivatives, analogs of normal sugar derivatives, were conveniently synthesized using 1‐methoxy‐2‐phospholene 1‐oxide as a starting material. All compounds were structurally characterized by their spectral data, and stereochemistry was determined by spectral and X‐ray crystallographic analyses.

An x-ray crystallographic analysis was carried out for Boc-(Aib-DeltaZPhe)4-Aib-OMe (1: Boc = t-butoxycarbonyl; Aib = alpha-aminoisobutyric acid; DeltaZPhe = Z-alpha,beta-didehydrophenylalanine) to provide the precise conformational parameters of the octapeptide segment -(Aib-DeltaZPhe)4-. Peptide 1 adopted a typical 3(10)-helical conformation characterized byphi= +/-55.8 degrees (50 degrees -65 degrees),psi= +/-26.7 degrees (15 degrees -45 degrees), andomega= +/-179.5 degrees (168 degrees -188 degrees) for the average values of the -(Aib-DeltaZPhe)4- segment (the range of the eight values). The 3(10)-helix contains 3.1 residues per turn, being close to the "perfect 3(10)-helix" characterized by 3.0 residues per turn. NMR and Fourier transform infrared (FTIR) spectroscopy revealed that the 3(10)-helical conformation at the atomic resolution is essentially maintained in solution. Energy minimization of peptide 1 by semiempirical molecular orbital calculation converged to a 3(10)-helical conformation similar to the x-ray crystallographic 3(10)-helix. The preference for a 3(10)-helix in the -(Aib-DeltaZPhe)4- segment is ascribed to strong inducers of the 3(10)-helix inherent in Aib and DeltaZPhe residues-in particular, the Aib residues tend to stabilize a 3(10)-helix more effectively. Therefore, the -(Aib-DeltaZPhe)4- segment is useful to rationally design an optically inactive 3(10)-helical backbone, which will be of great importance to provide novel insights into noncovalent and covalent chiral interactions of a helical peptide with a chiral molecule.

An efficient method is described in the synthesis of several novel deoxy phospha sugar pyrimidine nucleosides in racemic form, analogs of normal sugar nucleosides, in high yields by treatment of (±)-2-aminophospholane 1-oxide with several, α-cyano-, -acetyl-, -ethoxycarbonyl-β-ethoxy-N-ethoxycarbonylacrylamides.

A new type of polyaromatic dendrimer composed of six anthracene groups was synthesized, which showed a monomeric fluorescence feature with a diminished quantum yield due to intramolecular self-quenching processes in the dendritic framework.

A convenient and facile chemo- and regioselective oxidation of the allylic methylene group in a 2-phospholene ring system afforded the novel carbonyl derivatives of 2-phospholenes (2a–i). The method gives high conversion and selectivity in the formation of allylic ketones. The advantages of this oxidation method in such a five-membered pseudo sugar 2-phospholene ring are mentioned, and the oxidation is examined on several substituted 2-phospholenes (1a–i). © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:320–325, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10154

Novel pentofuranose analogs of phospha sugar derivatives were synthesized starting from 1-phenyl-2-phospholene 1-oxide ( 1 ). First, the allylic oxidation of 1-phenyl-2-phospholene 1-oxide ( 1 ) with CrO 3 in Ac 2 O-AcOH or 3-hydroxy-1-phenyl-2-phospholene ( 2 ) with MnO 2 afforded 1-phenyl-4-oxo-2-phospholene 1-oxide ( 3 ). The C-5 alkylation of 3 in the presence of NaH by using benzyl bromide or methyl iodide as electrophiles afforded the target title compounds.

Several novel 1-(substituted phenyl)-2-phospholene 1-oxide derivatives, which are analogs of sugars having a phosphorus atom in place of the ring oxygen of normal sugars, were synthesized from the corresponding 2-phospholenes as the starting materials. Structures of all the synthesized compounds were unequivocally confirmed by IR, 1 H, 13 C, and 31 P NMR spectral, elemental, and X-ray crystallographic analyses.

The synthesis of the novel 1-(substituted phenoxy/phenyl)-2-phospholene and phospholane 1-oxide derivatives, which are analogs of sugars having a phosphorus atom in place of the ring oxygen of normal sugars, is described. All of the synthesized derivatives are structurally characterized by multi nuclear NMR, mass, and IR spectral data, elemental and X-ray crystallographic analyses.

Allylic oxidation of 2-phospholenes gave the first successful preparation of 4-oxo-2-phospholene 1-oxide derivatives, and this synthetic approach provides a ready accessible route in the synthesis of a wide variety of pentofuranose analogs of phospha sugars, having a phosphorus atom as the sugar ring hetero atom.

Several novel phospha sugar nucleosides, analogs of normal sugar nucleosides, were synthesized from a phospholene 1-oxide derivative. Bromination of a phospholene precursor in aqueous organic medium gave regio diastereomers, the threo and erythro bromohydrins 3 (1-bromo-1,3,4-trideoxy-1,4-C-[(R,S)-phenylphosphinylidene]-glycero-tetrofuranose). Further substitution of the threo isomer 3a with sodium azide led to its corresponding azidophospholane 4 (1-azido-1,3,4-trideoxy-2-methyl-1,4-C-[(R)-phenylphosphinylidene]-beta-D-glycero-tetrofuranose). 1,3-Dipolar cycloaddition of 4 with various electron-deficient and electron-rich alkynes afforded triazole derivatives that are nucleoside analogues. The strong electron-withdrawing phosphoryl group in the hemiacetal ring exerted no effect over reaction regioselectivity of the 1,3-dipolar cycloaddition, but steric effects of the alkynes played a vital role on the selectivity, since the regioisomer ratios and the rates and yields of cycloadducts changed as the bulkiness of the substituents on the acetylene changes. Structures of all compounds were unequivocally confirmed by 1H, 13C, and 31P NMR and mass spectral studies. Single crystal X-ray crystallographic analysis of some derivatives allowed determination of configuration of the phospha sugar nucleosides.

In this paper we attempted to reveal how a large β-substituent (pyrenyl group) of dehydroresidue affects the structural and conformational preferences of (Z)-β-substituted α,α-dehydroalanine. An X-ray crystallographic analysis was carried out for Boc–L-Ala–ΔZPyr–L-Val–OMe (Boc = t-butyloxycarbonyl; OMe = methoxy) possessing a novel (Z)-β-(1-pyrenyl)dehydroalanine (ΔZPyr) residue. Single crystals were obtained by slow evaporation from an ethanol solution in the monoclinic space group P21. The bond lengths and bond angles of the ΔZPyr residue were essentially similar to other β-substituted dehydroalanines. The tripeptide took a type II β-turn conformation involving an intramolecular hydrogen bond between CO(Boc) and NH(Val), like small peptides possessing a (Z)-β-(1-naphthyl)dehydroalanine or a (Z)-β-phenyldehydroalanine residue. The similarity between ΔZPyr and other dehydroalanines in structural property and conformational preference should be responsible for the non-planarity of the ΔZPyr residue to give...

An X-ray crystallographic analysis was carried out for Boc-(Aib-ΔZPhe)2-Aib-OMe 1 and Boc-L-Pro-(Aib-ΔZPhe)2-Aib-OMe 2 (Aib = α-aminoisobutyric acid; ΔZPhe = α,β-dehydrophenylalanine; Boc = tert-butoxycarbonyl; OMe = methoxy) to provide detailed conformational data for oligopeptides possessing an -(Aib-ΔZPhe)2- segment. Both peptides adopted a typical 310-helical conformation characterized by = 52.8°, = 29.3°, and = -173.8° for the average values of the four residues of the -(Aib-ΔZPhe)2- segment in peptide 1, and = 54°, = 27°, and = -175° for those in peptide 2. The preference for a 310-helix in the -(Aib-ΔZPhe)2- segment is ascribed to the presence of Aib and ΔZPhe residues being strong inducers for the formation of a 310-helix. In peptide 2, the N-terminal L-Pro residue adopted a semiextended conformation, leading to a left-handed screw sense for the following achiral segment. This result was also supported by conformational energy calculation, in which the L-Pro residue leading to a left-handed 310-helical segment prefers a semiextended conformation rather than a right-handed helical conformation.

A new type of designed and functionalized ligand for a lanthanide ion based on dendritic architecture was synthesized. The dendrimers, which contain four and twelve glucose moieties on the molecular surfaces, were readily synthesized with good yields in every step. The NMR and GPC analyses precisely demonstrated successful constructions of the dendritic structures, while the formations of gadolinium chelates were deduced on the basis of HPLC study.

To understand how chemical structure of beta-substituted alpha, beta-dehydroalanine (particularly size and pi conjugation of beta substituent) affects conformational property, x-ray crystallographic analysis was performed on Boc-Ala-Delta(Z) Nap-Val-OMe [Boc: t-butoxycarbonyl; Delta(Z) Nap: (Z)-beta-(1-naphthyl)dehydroalanine; OMe: methoxy] having the naphthyl group as a bulky beta substituent. Single crystals were grown by slow evaporation from an ethanol solution in the triclinic space group P1 with a = 9.528 (3) A, b = 12.410(4) A, c = 5.975(2) A, alpha = 96.77(3) degrees, beta = 102. 81(2) degrees, gamma = 88.74(3) degrees, V = 684.1(4) A3, and Z = 1. Phase determination was carried out by a direct method (SHELEXS), and the final structure was refined to R = 8.1% and R(w) = 9.0% for 1964 observed reflections. The bond lengths and bond angles of the Delta(Z)Nap residue, characterized by a sp(2) hybridized C(alpha) atom, did not differ from those of other dehydroresidues such as Delta(Z) Phe, Delta(Z) Leu, and DeltaVal essentially. The peptide backbone took a type II beta-turn conformation involving an intramolecular hydrogen bond between CO(Boc) and NH(Val), similar to di- or tripeptides containing a Delta(Z) Phe or Delta(Z) Leu residue in the second positions. Here the naphthyl group was found to be nonplanar [chi(2) = 55(1) degrees ] relative to the C(alpha)==C(beta)==C(gamma) plane. The nonplanarity was supported by conformational energy calculation. The molecular packing was stabilized by two kinds of intermolecular hydrogen bonds and van der Waals interactions. Naphthyl groups were arranged in a partially overlapped face-to-face orientation with a center-to-center distance of 5.97 A. For additional information, peptide Boc-(Ala-Delta(Z) Nap-Leu)(2)-OMe was synthesized and its solution conformation was investigated by (1)H-NMR spectroscopy. The hexapeptide showed the tendency to form a 3(10)-helical conformation in solution essentially. Conformational properties of Delta(Z) Nap residue, characterized by a type II beta-turn and 3(10)-helix, were supported by a conformational energy contour map of the Delta(Z)Nap residue.

The synthesis and structure of novel glycoside and nucleoside derivatives of phospha sugar analogs from phospholenes are reported. 1-Phenyl-2-phospholene 1-oxide was regio-and diastereo-selectively converted into a 2-bromo-3-hydroxyphospholane derivative by an action of bromine in aqueous media. The reaction of the 2-bromophospholane derivative with some amines afforded 2-amino derivatives, which were N-glycosides of phospha sugar analogs. The 2-bromophospholane derivative was also converted into the corresponding azido derivative by the replacement of the 2-bromo substituent with sodium azide. 1,3-Diploar cycloaddition of the azido derivative with alkynes afforded phospha sugar nucleoside analogs which have a triazole ring as a nitrogen heterocycle.

3-Methyl-1-phenyl-2-phospholene and 1-phenyl-2-phospholene 1-oxides were converted into 2-bromo-3-hydroxy-3-methyl-1-phenylphospholane and 2-bromo-3-hydroxy-1-phenylphospholane 1-oxide (1-bromo-1,3,4-trideoxy-1,4-C-[(R, S)-phenylphosphinylidene]-glycero-tetrofuranose) by the action of bromine in aqueous medium. The bromo substituent of the phospholane was substituted by treatment with amines or an azide anion to afford novel glycoside derivatives of phosphanyl sugar analogs such as 2-amino-3-hydroxy-1-phenylphospholane (3,4-dideoxy-1,4-C-[(R, S)-phenylphosphinylidene]-glycero-tetrofuranosylamine) and 2-azido-3-hydroxy-3-methyl-1-phenylphospholane 1-oxides with retention of the configuration. The 1,3-dipolar cycloaddition of the 2-azido derivative of the phospholane with alkynes gave 3-hydroxy-3-methyl-1-phenyl-2-(triazol-1′-y1)phospholane 1-oxides as a novel triazole-derived nucleoside of phosphanyl sugar analogs. The structure of the glycoside and nucleoside derivatives of the phosphanyl sugar a...

A unique family of 1,3,8,10-tetrahydro-2,9-diazadibenzo[cd,lm]perylenes (THDAP) was prepared through a new synthetic strategy. Completion of the synthesis was achieved in several steps from commercially available perylene-3,4,9,10-tetracarboxylic dianhydride via reactions between 3,4,9,10-tetra(chloromethyl)perylene and primary amines. The successful use of a variety of primary amines in the reactions indicated that the synthetic approach provides a rich opportunity to produce new functionalized perylene derivatives.

X-ray crystallographic analyses were performed on single crystals of 1,2,3,4-tetra-O-acetyl-5-deoxy-5-C-(isopropylphosphinyl)- d -ribopyranoses, 1,2,3,4-tetra-O-acetyl-5-deoxy-5-C-(isopropylphosphinyl)- d -xylopyranoses, and 1,2,4-tri-O-acetyl-5-deoxy-3-O-methyl-5-C-(phenylphosphinyl)- d -ribopyranoses. These compounds have the (RP) configuration at the phosphorus atom with the 4C1 conformation of the pyranose ring, and the conformation supported by NMR studies.

Some phosphanyl sugar derivatives, which are analogs of sugars having a phosphorus atom in place of the ring oxygen, were synthesized from 2- and 3-phospholenes as starting materials. Catalytic cis-dihydroxylation of 2-phospholene or 3-phospholene 1-oxide derivatives with osmium(VIII) oxide in the presence of a cooxidant afforded 3-deoxy- or 1-deoxy-tetrofuranose-type phosphanyl sugar derivatives, respectively. cis- Dihydroxylation of 4-acyloxy-2-phospholene 1-oxide derivatives gave tetrofuranose type phosphanyl sugar derivatives. Some of these derivatives of phosphanyl sugars were subjected to structural analyses using 1H NMR and X-ray crystallography. 1. Presented at the XVIIIth Inlernational Carbohydrate Symposium, Milan, Italy, July 21-26, 1996.

2- And 3-phospholenes were used as the starting materials for the syntheses of sugar derivatives having a phosphorus atom in the hemiacetal ring of the sugar derivatives (phosphono sugars). Alkylation or benzyloxymethylation of 3-phospholene 1-oxides afforded phospholene derivatives with more than 5 carbon atoms. Epoxidation followed by epoxide ring opening and cis-dihydroxylation of 5-benzyloxymethyl-2-phospholene derivatives afforded four pentofuranose type phosphono sugars (arabinose, lyxose, ribose, and xylose). Some nucleosides and isonucleosides of phosphono sugars were also prepared. Some of these derivatives of phosphono sugars were subjected to structure elucidation and bioassay.

A convenient synthetic approach is established to prepare a new class of 1- l -α-amino acid derivatives of phospholene oxides by amination of (±)-1-chloro-2-phospholene-1-oxides with several optically pure l -α-amino acid esters. All compounds obtained as a diastereomeric mixture in good to high yields. The two diastereomers were successfully separated by column chromatography and structurally identified by their spectral analyses.

A novel method has been developed for stereospecific conversion of 2-phospholene 1-oxides into their corresponding 2,3-epoxides in high yields using sodium peroxide as a reagent.

Stereoselective reactions of 1-methoxy-3-phospholene 1-oxide gave a novel 1-deoxy phosphono sugar, whose relative configuration was confirmed by X-ray crystallography. Further reaction of the 1-deoxy phosphono sugar with phthalimide and 6-chloropurine produced novel phosphono sugar nucleosides.

Some new 4-bromo-2-phospholene 1-oxides (IV) are synthesized by allylic radical bromination of 2-phospholene oxides (III).

Reactions of 1-phenyl- and 1-methoxy-2-phospholene 1-oxides with bromine in aqueous organic solvents or in a protic medium, such as methanol, easily afforded the corresponding 2-bromo-3-hydroxy- or 2-bromo-3-methoxyphospholane 1-oxide derivatives. The reaction mechanism was postulated based on the stereochemistry of the products.

Reaction of 2-bromo-3-hydroxy-1-methoxy-3-methylphospholane 1-oxide with silylated 2-hydroxypyridine gave a novel non-natural phosphono sugar nucleoside derivative.

Treatment of 1-alkoxy-3-phospholene 1-oxide with lithium diisopropylamide followed by novel stereoselective C-alkylation with alkyl halides afforded 2-alkyl-and 2-benzyloxymethyl-3-phospholene 1-oxides, which were subjected to osmium (VIII) oxide-catalyzed diastereoselective cis-dihydroxylation to give new C-glycoside derivatives of Furanose-type phosphono sugars, with twist conformation.

Optically active (S)-2-aminopropylphosphonic and (S)-2-amino-4-methylpentylphosphonic acids were synthesized from commercially available chiral α-amino acids [(S)-(+)-alanine and (S)-(+)-leucine] without racemization.

Reactions of 2-phospholene 1-oxides with N-bromoacetamide in aqueous organic solvent produced 2-bromo-3-hydroxyphospholane 1-oxides, which reacted with sodium salts of dialkyl phosphonates to afford novel 2-phosphinoylphospholane 1-oxide derivatives. A 4-phosphin-oyl-2-phospholene derivative was also prepared.

Treatment of 1-alkoxy-3-phospholene 1-oxide with lithium diisopropylamide followed by novel stereoselective C-alkylation with alkyl halides afforded 2-alkyl-and 2-benzyloxymethyl-3-phospholene 1-oxides, which were subjected to osmium (VIII) oxide-catalyzed diastereoselective cis-dihydroxylation to give new C-glycoside derivatives of Furanose-type phosphono sugars, with twist conformation.

Reaction of 2-bromo-3-hydroxy-1-methoxy-3-methylphospholane 1-oxide with silylated 2-hydroxypyridine gave a novel non-natural phosphono sugar nucleoside derivative.