Novel Synthesis and Structure of Phosphanyl Sugar Derivatives 1

Abstract

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.

     

SYNTHESIS AND CONFORMATIONAL STUDIES OF A NUMBER OF SATURATED BICYCLIC SIX-MEMBERED RING PHOSPHITES

Abstract

An ¹H NMR study of the conformation of the dioxaphosphorinane ring of a number of diastereoisomeric bicyclic saturated six-membered ring phosphites (3ab-10ab) has been performed. The dioxaphosphorinane ring of these phosphites is transannelated with a tetrahydrofuran, cyclopen-tane, tetrahydropyran or cyclohexane ring. The substituent on the phosphorus atom is a methoxy or phenoxy group. It is shown that the cis isomers 3a-10a prefer a chair conformation of the dioxaphosphorinane ring, independent of the substituent on the phosphorus atom and of the nature of the transannelated ring. In contrast, for the trans isomers 3b-10b a twist rather than a chair conformation of the dioxaphosphorinane ring is preferred. The fraction of the twist conformer in the trans isomers is mainly determined by the substituent on phosphorus. The size and composition of the transannelated ring are relatively unimportant in this respect. For both cis and trans isomers the preferred geometry is solvent-independent. The measured ^3JPOCH couplings of the cis isomers 3a-10a are used to formulate an expression for the dependence of such couplings upon dihedral angles in bicyclic phosphites.     

The Effect of Trifluoroethoxy Groups on the Structures of Eight-Membered Ring-Containing Cyclic Phosphites 1

New phosphites 1–4 were synthesized from phosphorus trichloride and an appropriate diphenol followed by the addition of trifluoroethanol in the presence of triethylamine. These phosphites are to serve as precursors in the syntheses of biorelated hypervalent phosphoranes. ¹H, ¹⁹F, and ³¹P NMR spectra were recorded. X-ray analysis of 3 and 4 revealed that the sulfur-containing eight-membered ring was in a syn conformation that a allowed a sulfur donor interaction to the phosphorus atom, whereas for phosphite 2, the eight membered sulfonyl containing ring was in an anti conformation that did not allow a donor interaction to phosphorus from the oxygen atom of the sulfonyl group. Structural comparisons are made with related cyclic phosphites and phosphates having donor atoms in eight-membered rings.     

Construction of the 17-Thiasteroid Ring System by the Diene-Sulfur Dioxide Cycloaddition Reaction

Abstract

We recently showed² that the steroid ring system can be constructed with a phosphorus atom replacing a carbon in the D-ring by the cycloaddition of a phosphorus (III) halide with a diene that is a vinyl dihydrophenanthrene derivative, such as (1). The phosphine oxide (3) resulting from the hydrolysis of the initial cycloadduct (2) has some resemblance to the hormone equilenin, which also has rings A and B in naphthalene form.     

Formation and Crystal Structure of 4,4'-Oxybis(2,6-bis(dimethylamino)-4H-1,3,5,4-thiadiazaphosphinine 4-Oxide)

Abstract

The reaction of P₄S₁₀ with dimethyl cyanamide as solvent yields a complex mixture of products, from which the new compound 4,4′-oxybis(2,6-bis(dimethylamino)-4H-1,3,5,4-thiadiazaphosphinine 4-oxide) (1) was isolated. In this pyrophosphate derivative, the phosphorus atoms are part of the, otherwise rarely encountered, 1,3,5,4-thiadiaza-phosphinine ring. The molecular structure of the new compound was elucidated by single-crystal X-ray diffraction, showing an almost planar thiadiazaphosphinine ring and a cis-like arrangement of the heterocycles at the two phosphorus atoms.     

Novel chain and ring polyphosphorus compounds

Abstract

Compounds with a skeleton of phosphorus chains or rings have been rare until recently, as they are in general highly reactive. Nevertheless, considerable progress has been achieved in this field lately, especially regarding three-membered phosphorus ring compounds, metalated phosphorus hydrides and polycyclic organophosphanes.     

Synthetic,Fungicidal Unsaturated-γ-lactones Attached to Furanosidic Systems. Configurational Determination by Nuclear Overhauser Effect1

Abstract

Stereoselective synthesis of a butenolide sugar derivative was possible by reaction of the appropriate sugar epoxide with the dilithium salt of phenylselenoacetic acid, followed by oxidation of the α-phenylselenobutanolide obtained with hydrogen peroxide in the presence of catalytic amounts of acetic acid. On the other hand, synthesis of an exocyclic α,β-unsaturated lactone was accomplished by Reformatsky reaction on the appropriate sugar carbonyl groups with ethyl bromomethylacrylate and activated zinc, leading to the introduction of this ring at position 2 or 4 of a furanose ring. Nuclear Overhauser effect studies led to the unambiguous determination of the configuration of the new chiral centre formed by the Reformatsky reaction. The fungicidal efficacy of some unsaturated lactone sugar derivatives is given.     

Reaction of 2-cyano[(4-oxo-4H-chromen-3-yl)methylidene]acetohydrazide with phosphorus reagents: Synthesis and evaluation of anticancer activities of some novel 1,2-azaphospholes, 1,2,3-diazaphospholidine,and 1,3,2-diaza-phosphinanes bearing a chromone ring

A series of 1,2-azaphospholes, 1,2,3-diazaphospholidine, 1,3,2-diaza-phosphinanes bearing a chromone ring as well as dialkyl pyrazolopyrimidine phosphonates have been synthesized from treatment of multifunctional 2-cyano[(4-oxo-4H-chromen-3-yl)methylidene]acetohydrazide (2), some phosphorus reagents such as phosphonic acid and its esters, and phosphorus sulfides as well as phosphorus halides in dry dioxane. The isolated products were evaluated for their anticancer activities and on the expression of vascular endothelial growth factor (VEGF) inhibition. Among the isolated products, compounds 3 and 10 exhibited higher effect against breast cancer cells than the reference drug and on the expression of VEGF inhibition.     

Dihydrazidophosphoric Acid Derivatives as Starting Materials for Inorganic Heterocycles with Unusual Ring Conformations

Abstract

Reported are synthetic routes to inorganic heterocycles of different ring size, containing phosphorus, hydrazine, silicon and other elements as ring components. Steric effects that cause saturated sixmembered rings to adopt an unusual twist conformation are discussed (temperature dependent NMR-spectra, X-ray structures).     

MASS SPECTRA OF PERACETYLATED DERIVATIVES OF SUGAR ANALOGUES HAVING PHOSPHORUS IN THE HEMIACETAL RING

Abstract

The first, detailed analysis of the mass spectra of the title compounds having a pyranoid or furanoid ring was carried out. The molecular-ion intensities of these phosphorus sugars were shown to be higher compared to the oxygen analogues, thus permitting accurate mass measurement. The main fragmentation pathway was the consecutive loss of the substituents from ring carbon atoms and C-6 (the A series of fragmentation), leading to the formation of 1,2-dihydro-λ⁵-phosphorin or -phosphole oxide derivatives. Possible degradation pathways of the phosphorus-containing ring to acyclic fragments are also discussed. These findings are considered to be of use in structural analysis of these phosphorus sugars.     

Conversion of Cyclic Phosphorothioates into Halophosphates and Neutral Phosphorus Esters and Amides

Abstract

Cyclic phosphorus esters and amides in the 1,3,2-dioxaphosphorinane-2-one series are usually obtained by the condensation of a diol with a suitable phosphorus oxyhalide. In the case of dissymetric diols the formation of two diastereoisomeric products, epimeric at phosphorus, can be expected. This procedure failed or proceeded with low yields when applied to the preparation of cyclic phosphates which would lead to the formation of sterically strained dioxaphosphorinane ring.¹     

Polyphosphorus Compounds: Recent Synthetic and Structural Results

Abstract

Various new phosphorus six-, five-, and three-membered ring compounds as well as polycyclic organophosphanes and the silaphosphacubane (t-BuSiP) have been synthesized and structurally characterized.⁴     

Application of Sugar Phosphonates for the Preparation of Higher Carbon Monosaccharides

ABSTRACT

Reaction of sugar derived phosphonates [Sug-C(O)CH₂P(O)(OMe)₂] with sugar aldehydes (Sug'-CHO) provides the higher enones of the general formula Sug-C(O)CH=CH-Sug' with the trans configuration of the double bond. The phosphonate method is superior to the previously used phosphorane methodology [Sug-C(O)CH=PPh₃ + Sug'-CHO] since sugar phosphonates can be prepared in much higher yields and are much more nucleophilic than corresponding phosphoranes. The sugar enones are reduced to appropriate allylic alcohols with zinc borohydride; the stereoselectivity of this process is >97:3 (with the D-glycero isomer predominating) when the carbonyl group is placed at the α-position to the sugar ring. CD spectroscopy was used for the determination of the configuration of higher sugar allylic alcohols.     

Novel Synthesis of Macrocylic Systems Containing Phosphorus and Sulfur

Abstract

Macrocyclic systems containing phosphine. phosphoryl or thiophosphoryl functions in the ring demonstrate high ability to complex metal ions Complexed structures of this type show interesting Fatalytic properties and can be used in homogenous and heterogenous catalysis^[1,2] Macrocyclic compounds containg phosphorus are also useful as complexing agents for ammonlum salts. anions. etc [3,4] Generally three types of reactions are used to synthesize phosphorus containing macrocyclic compounds the cyclocondensation, the ring opening reaction and the reaction with metal as a matrix^[5]. We have devoloped a new procedure for the synthesis of the title systems of different sizes and of different P and S contents It is based on a double conjugate addition of dithiolates to divlnyl phosphine oxides and sulfides and makes use of the so-called “cesium effect”.     

Synthesis and Conformational Analysis of 1, 2-Anhydro-3, 4-di-O-benzyl-6-deoxy-α-D-glucopyranose

Abstract

The title 1, 2-anhydro sugar (10) was synthesized from methyl 4, 6-O-benzylidene-α-D-glucopyranoside or from 1, 2-O-ethylidene-α-D-glucopyranose. The key intermediate for the synthesis was 2-O-acetyl-3, 4-di-O-benzyl-6-deoxy-β-D-glucopyranosyl fluoride (8)which was transformed into the target compound by ring closure with potassium tert-butoxide. Calculations by the modified Karplus equation from vicinal coupling constants of 10 suggested that the conformation of 10 was almost an ideal ⁴ H ₅ for the pyranose ring. Conformational analysis for the 1, 2-O-(R)-ethylidene intermediates 17 and 20 revealed that their pyranose ring basically adopted a B₂,₅ conformation.     

Attempts to Rationalize the Chemical Reactivity of the 1–3 Dipolar Species Obtained when a Phosphite Reacts with Activated Ethylenic or Acetylenic Ketones or Esters

Abstract

- Addition of trivalent phosphorus compounds with α, β ethylenic ketones and esters leads to examples of prototropy or cyclisation or rearrangement with ring expansion from 5 to 7 atoms.

When trivalent phosphorus compounds react with acetylenic ketones and esters, the 1, 3 dipolar species can be trapped with an electrophilic reagent (aldehydes or the original acetylenic compound) or a protic reagent (alcohol, acid, amide, phenol, etc…) Ylides, phosphoranes, spirophos-phoranes and phospholes can be obtained.     

Intramolecular Diastereoselective Cascade Cyclization Reaction of N,N′-Bis(Salicylidene)Cyclohexanediimine with Phosphoryltrichloride to a Bis(Chlorophosphorylated) Decahydro-2,4-DI (2-Hydroxyphenyl)Benzo[d][1,3,6]oxadiazepine

Abstract

A new type of cascade cyclization was observed in the phosphorylation reaction of (R,R)- or (S,S)-N,N′-bis(salicylidene)cyclohexanediimine with phosphoryltrichloride, which resulted in the formation of bis(chlorophosphorylated) decahydro-2,4-di(2-hydroxyphenyl)benzo[d][1,3,6]oxadiazepine with two new stereogenic phosphorus atoms and two new stereogenic carbon atoms in the oxadiazepine ring in the β-position to phosphorus. During the synthesis, the N atom attacks the phosphorodichloridate group with the formation of the P–N bond to give an asymmetric phosphorus atom and an iminium ion. This compound with six stereogenic centers crystallizes in the monoclinic centrosymmetric space group P2₁/c and the crystal structure together with solution and solid-state MAS ¹³C and ³¹P NMR studies reveals a preferential formation of stereoisomers.     

Azaphospholes1,2: State and Advances

Abstract

Heterophosphole³ derive from the classical nitrogen, oxygen or/and sulfur containing five-membered 6n-heterocycles by replacing a CH unit by two-coordinate phosphorus as a member of the ring. Formally 4 8 systems seem possible this way. Of 21 of them representatives have been prepared so far⁴.     

Exocyclic Diastereotopic Protons as a Probe for Conformational Bias in Eight-Membered Rings Containing Phosphorus and Titanium

Abstract

The conformation in solution of eight-membered 12H-dibenzo[d,g][1,3,2]-dioxametallocin rings containing phosphorus and titanium, respectively, were studied by the NMR spectroscopy using ring substituents containing diastereotopic protons as a probe for conformational bias. The results of this study suggest that in addition to steric effects, an electronic effect due to donation of the lone pair of electrons on the ring oxygen atoms to the metal center influences the preferred conformation in solution.     

Studies of the Synthesis of Rubranitrose and Crystal Structure of Methyl 2,3,6-Trideoxy-3-C-Methyl-3-Nitro-α-D-Ribo-Hexopyranoside

Abstract

The branched-chain nitro sugar methyl 2,3,6-trideoxy-3-C-methyl-3-nitro-α-D-ribo-hexopyranoside 4 was investigated as a precursor to D-rubranitrose, a nitro sugar found in the antibiotic rubradirin. X-ray cyrstallographic analysis of 4 shows that the pyranose ring adopts the ⁴ C ₁ conformation with the methoxy group at C-1 and the nitro group at C-3 in a 1,3-diaxial relationship. There is an intermolecular hydrogen bond involving a nitro group oxygen of one monosaccharide residue and the C-4 hydroxyl group of the adjacent residue in the crystal lattice. This interaction results in a helical crystal packing. A series of nucleophilic displacement reactions was carried out on the triflate derivative of 4 in an attempt to introduce an axial carbon-oxygen bond at C-4 required for rubranitrose. Displacements with acetate and propionate gave as products the monosaccharide esters with the desired D-xylo configuration.