Guy Guerch

An answer to the spiro versus ansa dilemma in cyclophosphazenes: Part III. N3P3Cl5[HN(CH2)4NH]Cl5P3N3. A serendipitous two-ring bridged-assembly phosphazene

Abstract Reaction of N 3 P 3 Cl 6 with butylenediamine (1:1) leads to a mixture of the expected mono spiro compound as the major product and of two by-products (A) and (B). Mass spectrometry and X-ray analysis prove that (A) has a two-ring assembly structure in which two N 3 P 3 Cl 5 moieties are bridged through a [HN(CH 2 ) 4 NH] entity.

An answer to the spiro versus ansa dilemma in cyclophosphazenes: Part IV. Reaction of spermidine and spermine on N3P3Cl6

Abstract Reactions of N3P3Cl6 with spermidine and spermine lead to unique final products in which two new types of configuration for the polyamino ligand, called SPIROBINO and DISPIROBINO respectively, are made conspicuous by concerted use of high resolution NMR, mass spectrometry and X-ray analysis. The product obtained by reaction of spermine on N3P3Cl6 is [N3P3Cl4HN(CH2)3N(CH2)2]2. It crystallizes in the monoclinic system, space group P21/c. The cell parameters are a=10.397(2), b = 7.869(2), c = 17.898(3) A, β = 102.1(1)°, V = 1431.6(4) A3, Z = 2 (considering the dimer), Dc = 1.748 Mg m−3, 2814 unique reflections, R = 0.042. The crystal structure shows a two-ring bridged-assembly DISPIRO pattern.

An answer to the spiro versus ansa dilemma in cyclophosphazenes: Part I. N3P3Cl4[NH(CH2)3NH]

Abstract Structural investigation, mainly by mass spectrometry and X-ray crystallography, of the product obtained from the reaction of propylenediamine and N 3 P 3 Cl 6 shows it to have a monospiro structure. It is demonstrated that in this case data collected through indirect structural methods such as IR or NMR spectroscopy could not provide a priori the right answer.

An answer to the spiro versus ansa dilemma in cyclophosphazenes

Abstract A structural investigation mainly, by mass spectrometry and X-ray crystallography, of the products obtained from reaction of butylenediamine and N3P3Cl6 shows that the major product is unambiguously the spiro derivative N3P3Cl4[HN(CH2)4NH], the disipiro compound N3P3Cl2[HN(CH2)4NH]2 being observed as side-product. Thus, butylene-diamine behaves like propylenediamine and ethylenediamine although the yield of the main monospiro product decreases significantly as the length of the methylenic chain of the diamine increases.

Attempts at the production of more selective antitumourals: Part I. The antineoplastic activity of cyclophosphazenes linked to the polyamines 1,3-diaminopropane and 1,4-diaminobutane (putrescine)

Abstract In an attempt to design antitumour cyclophosphazenes of improved specificity by linking them to some natural tumour finders, we studied the binding of gem-N 3 P 3 Az 4 Cl 2 to 1,3-diaminopropane and 1,4-diaminobutane (putrescine). Synthesis, mass spectrum and NMR as well as X-ray crystal structures of the two spirocyclic N 3 P 3 Az 4 [HN(CH 2 ) 3,4 NH] derivatives (in which the N 3 P 3 Az 4 active principle is linked to the diamine in a spiro configuration) are described. Results obtained with these compounds in 3 murine tumour systems (L1210 and P388 leukaemias and P815 mastocytoma), showing their potent antineoplastic activity in vivo obtainable at well-tolerated doses, are also described.

An answer to the SPIRO versus ANSA dilemma in cyclophosphazenes. Part VII. Neither SPIRO nor ANSA: the BINOdicyclotriphosphazenes, N3P3Cl5 [HN(CH2)nNH] Cl5P3N3

Abstract Reactions of N 3 P 3 Cl 6 with cadaverine, H 2 N(CH 2 ) 5 NH 2 , and higher cousins lead to unique final products in which two N 3 P 3 Cl 5 moieties are bridged through a [HN(CH 2 ) n NH] entity in a two-ring assembly structure. This new type of configuration for the diamino-ligand, called BINO, is made conspicuous by concerted use of mass spectrometry and 31 P, 13 C and 1 H high resolution NMR.

202 MHz 31P NMR performances

Abstract 202 MHz 31 P NMR performances are illustrated for structural investigation of new precursors of anticancer immuno-modulating agents within the cyclophosphazenic series.

The Antineoplastic activity of 2,2,4,4-tetrakis(aziridinyl)-6,6,-dichlorocyclotriphosphaza-1,3,5-triene, gem-N3P3Az4Cl2, a novel anticancer agent

Abstract Synthesis, Mass spectrum, N.M.R., IR and Raman data as well as X-Ray crystal structure of a new anticancer cyclophazene, namely gem-N3P3Az4Cl2 (Az = Aziridinyl), are described. Antitumor activity in vivo of this chemical on 5 rodent tumors was found comparable to the ones of N3P3Az6 (MYKO 63) and N3P2SOAz5 (SOAz). In view of its activity, gem-N3P3Az4Cl2 constitutes a starting material for the synthesis of intramolecular combinations with (NH)-bearing antitumor drugs (which may possess synergic activities).

202 MHz 31P NMR performances: Part III. Conformational analysis of {[HN(CH2)mNH]N3P3Cl3}2 - [HN(CH2)nNH] (with m = 3,4) cyclophosphazenic species

Abstract 202.458 MHz 31 P NMR reveals two conformations which co-exist 50:50 (no interconversion barrier) at ambient temperatures in the title compounds. Dilution experiments show that splittings of such ABC systems (3 doublets of doublets) are due to intramolecular hydrogen bonding between Cl atoms of one ring and N(H) atoms of the other with folded conformations preferred.

Spermidine-linked cyclophosphazenes: new spiransa configurations☆

The spermidine-linked innate SPIRO-BINO configuration is commonly obtained by adding spermidine to hexachlorocyclotriphosphazene N3P3Cl6. Conversely, addition of N3P3Cl6 to spermidine in (1:2) stoichiometry and high dilution conditions (CHCl3) yields a new merged SPI-RANSA structure in a quite neat way, in a few hours and at room temperature. Aminolysis of this new SPIRANSA species leads to compounds which partly obey BASIC classical rules.