Roger Lahana

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 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 .5. the Dispiro N3p3cl2 [hn-(ch2)3,4-nh]2 and Trispiro N3p3 [hn-(ch2)3-nh]3 Derivatives

Abstract The reaction of N3P3Cl6 with 1,3-diaminopropane and 1,4-diaminobutane (putrescine) in suitable non-polar solvents allows the synthesis, with a very high yield of the PN H R-containing DISPIRO and TRISPIRO derivatives without any significant side-polymerization.

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.

An answer to the SPIRO vs. ANSA dilemma in cyclophosphazenes. VI. The first polyspirodicyclotriphosphazenes

Abstract Synthesis of the first polyspirodicyclotriphosphazenes was achieved (i) upon reaction of 1,3-diaminopropane on the product of the reaction of N3P3Cl6 with spermine (direct route), and (ii), upon reaction of spermine on spiro-N3P3Cl4[HN(CH2)3NH] and dispiro-N3P3Cl2[HN(CH2)3NH]2 derivatives (reverse route). The whole compounds were obtained in a monomeric state and with high yield, thanks to the use of a sharp (3:7) mixture of methylene chloride and 60–80 °C light petroleum as solvent. EI and DCI mass spectrometry techniques were used together with 31P NMR data to assign molecular structures.

Analyse conformationnelle theorique et activite anti-depressive de nouveaux derives cyclopropaniques bifonctionnels: Midalcipran et isomeres

Abstract (Theoretical conformational analysis and anti-depressive effectiveness of new bifunctional cyclopropanic derivatives: Midalcipran and relatives) The conformational analysis of Midalcipran, a novel anti-depressor agent, was achieved through a concerted use of the CNDO/2 quantum technique and of some new specific software for micro-computers, such as APPLE ///, which are able to design and sort preferred conformations. The anti-depressive activity is then attributed to the existence in the molecule of a “double-locked” rigid lactamic pattern highly suitable for receptor recognition.

Vibrateur NH et activité antitumorale des cyclophosphazènes vectorisés par des polyamines biogènes

Abstract A comparative i.r. spectroscopic study of NH groups in natural polyamines both free and covalently bound to antitumor cyclophosphazenes allows one to explain the remarkable selectivity towards malignant cells of such drugs when vectorized through such polyamines as tumor finders and to classify the targeting potentiality of these polyamines as a function of the various configurations they adopt when linked to the cyclophosphazenic antitumor agents.

How to use a very simple microcomputing system for a dynamical conformational analysis of versatile molecules. The case of some anticancer inorganic ring systems

Abstract A very simple use of a suitable microcomputing system allows discrimination of a set of X-ray structures of anticancer drugs which (i) are the “natural” preferred conformations and (ii) are the direct relationships logically linking these conformations together. Such an approach appears the main interest for a deep understanding of the relative antitumour activities of drugs, whatever the target may be.

Cyclophosphazenes and Relatives as Anticancer Drugs

Abstract Aziridinocyclophosphazenes N3P3Az6 (code name MYKO 63), N4P4Az8 (code name MYKO 83) and relatives constituted the first generation of anticancer drugs whose efficiency on several rodent neoplasms was made conspicuous in a quantitative manner from 1976 to 1978 both in our Laboratory and by EORTC Screening Pharmacology Groups1. MYKO 63 appeared at that time as a promising drug for industrial development owing to its wide spectrum of activity and its very low mutagenicity2. However, this hope failed as a consequence of a cumulative toxicity which occurs upon heavy polyinjections schedules. In other words, MYKO 63 exhibits an uncomfortable kinetics of action on the tumor - and, consequently, of excretion - presumably due (it was our assumption) to a too high chemical stability of the molecule.