Valluru Krishna Reddy

Palladium- or Iridium-Catalyzed Allylic Substitution of Guanidines: Convenient and Direct Modification of Guanidines

As a convenient and direct functionalization of guanidines, the transition metal-catalyzed allylic substitution of guanidines was studied. The guanidine derivatives bearing two electron-withdrawing substituents acted as reactive nucleophiles in the allylic substitution to give the monoallylated products. The double allylic substitution was achieved by using tri-Boc-guanidine bearing three electron-withdrawing substituents as a nucleophile to give the diallylated products. The regiocontrol in the allylic substitution of unsymmetrical allylic substrates has been investigated by employing the palladium or iridium catalysts. The iridium complex of chiral pybox ligand allowed the regio- and enantioselective allylic substitution. Asymmetric double allylic substitution of tri-Boc-guanidine with phosphate bearing the 1-naphthyl group gave the diallylated product with high diastereo-, regio-, and enantioselectivities.

An efficient approach towards the stereospecific synthesis of epoxides from phospholene oxides

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.

An efficient synthesis of novel deoxy phospha sugar pyrimidine nucleosides

Abstract 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.

Synthesis of novel deoxy λ5 phospha sugar nucleosides: 1,3-dipolar cycloaddition of an azidophospholane with alkynes

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.

Preparation And Characterization Of Phospholanes And Phospha Sugars As Novel Anti-Cancer Agents

Diastereo isomeric erythro and threo forms of 2,3-epoxy-l-phenylphospholane 1-oxides were synthesized from threo and erythro forms of 2-bromo-3-hydroxy-l-phenylphospholane 1-oxides being prepared from l-phenyl-2-phospholene 1-oxide. Alternatively, the epoxides were also prepared by the epoxidation of the 2-phospholene with peroxides such as sodium peroxide and hydrogen peroxide. The reactivity and regioselectivity for the reaction of erythro and threo forms of the 2,3-epoxides with nucleophiles were investigated by using amines, and the reaction afforded 2-amino-3-hydroxy-l-phenylphospholane 1-oxides, which correspond to phospha sugar N-glycosides. 2,3-Dibromo-3-methyl-l-phenylphospholane 1-oxides were first prepared from 3-methyl-l-phenyl-2-phospholene 1-oxide. The prepared phospholanes or phospha sugars were biologically qualified by ΜΤΓ (3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide) in vitro method to find that some of these phosphorus heterocycles or phospha sugars have quite efficient anti-cancer activity for leukemia cells in manners of (i) wide spectra, (ii) high activities, and (iii) high specificities.

SYNTHESIS OF NOVEL PHOSPHA SUGAR DERIVATIVES VIA ALLYLIC OXIDATION OF 2-PHOSPHOLENES

ABSTRACT 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.

Synthesis of Novel 1-(substituted phenyl)-2-phospholene 1-Oxide Derivatives

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.

Facile Synthesis of Novel Pentofuranose Analogs of Phospha Sugar Derivatives

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.

SYNTHESIS OF NOVEL NITRO-SUBSTITUTED 1-PHENOXY-2-PHOSPHOLENES AND PHOSPHOLANES

Some nitro-substituted phenoxyphospha sugar 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. Catalytic c/s-dihydroxylation of the 2-phospholenes with osmium(VIII) oxide, protection of c/s-diol and some functional group interconversions gave tetrofuranose type phospha sugar derivatives which are possessing phosphorus ester functionality (0=P-0-) with a nitrophenyl group. These derivatives are structurally confirmed by spectral analyses. Introduction Replacement of the oxygen atom in the hemiacetal ring of normal sugars by a hetero atom or a carbon atom leads to pseudo sugars, some of which have been widely investigated in the fields of synthetic, biological, and medicinal chemistry. In particular hetero sugars in which the ring oxygen has been replaced by a nitrogen, sulfur, or selenium atom have been extensively studied and widely developed (1). Although aza and thia sugars are known to exist in nature, phospha sugar derivatives, having a Ρ atom in place of the ring oxygen, have not yet been found in naturally occurring products. Phospha sugars are of interest because of their potential biological activities (2). Therefore phospha sugar derivatives were of interest in the aspects related not only to synthesis and structures but also to biological activities. Phospha sugars containing a phenoxy groups being mainly nitro-substituted are expected to be possessing potential biological activities suggested by bio-active phosphorus compounds (3). Addition of phosphorus trihalides or phosphonous dihalides to 1,3-alkadienes is known to produce cyclic unsaturated phosphorus compounds, i.e., phospholenes (4, 5). In our earlier papers (6, 7), we reported the c/s-dihydroxylation of 2-phospholenes with a catalytic amount of osmium(VIII) oxide and cooxidants (7). The present paper deals with further conversion of phospha sugars into different substituted 1-nitrophenoxy phospholene and phospholane derivatives. Phospha sugars possessing phosphorus ester functionality (0=P-0-) with a nitrophenyl group has not yet been reported so far. Results and Discussion A pure compound of 1-chloro-3-methyl-2-phospholene 1-oxide (1) was prepared from 1methoxy-3-methyl-2-phospholene 1-oxide. Compound (1) was refluxed in dry toluene with nitrosubstituted phenols afforded 3-methyl-1 -(nitro-substituted phenoxy)-2-phospholene 1-oxides (2ac) (Scheme 1). In the same way 2,3-diacetoxy-3-methyl-1 -(nitro-substituted phenoxy)phospholane 1-oxides (4a-c) (Scheme 2) were prepared from 2,3-diacetoxy-1-chloro-3-methylphospholane 1-oxide (3). The products were purified by column chromatography on silica gel and the isomer ratios are calculated on the basis of P NMR. Attempts to prepare phospholanes Vol. 6, No. 4, 2000 Synthesis of novel nitro-substituted l-phenoxy-2-phospholenes and phospholanes (4a-c) from phospholenes (2a-c) were failed because of P-O-C bond was easily broken in aqueous medium due to strong electron withdrawing nature of P=0 bond (7) and negative inductive effect of nitrophenyl group. The alternative synthetic method shown in Scheme 2 was followed. These are the first phospha sugar derivatives which are possessing phosphorus ester functional moiety (0=P-0-) with a nitrophenyl group prepared from 2-phospholenes as the starting materials. The structure of 1-(nitro-substituted phenoxy)-2-phospholene and phospholane derivatives is supported by spectral data shown in Tables 1 and 2.

Preparation and Evaluation of Novel Sugar Dendritic Gd-DTPA Complexes for MRI Contrast Agents and Phospha Sugars for Anti-Tumour Agents

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.