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Current Organic Chemistry

Editor-in-Chief

ISSN (Print): 1385-2728
ISSN (Online): 1875-5348

Research Article

Synthesis, Conformational Analysis and Crystal Structure of New Thioxo, Oxo, Seleno Diastereomeric Cyclophosphamides Containing 1,3,2-dioxaphosphorinane

Author(s): Dorra Kanzari-Mnallah, Med L. Efrit, Jiří Pavlíček, Frédéric Vellieux, Habib Boughzala and Azaiez B. Akacha*

Volume 23, Issue 2, 2019

Page: [205 - 213] Pages: 9

DOI: 10.2174/1385272823666190213142748

Price: $65

Abstract

Thioxo, Oxo and Seleno diastereomeric cyclophosphamides containing 1,3,2- dioxaphosphorinane are prepared by a one-step chemical reaction. Their structural determination is carried out by means of Nuclear Magnetic Resonance NMR (31P, 1 H, 13C) and High-Resolution Mass Spectroscopy (HRMS). The conformational study of diastereomeric products is described. Density Functional Theory (DFT) calculations allowed the identification of preferred conformations. Experimental and calculated 31P, 13C, 1H NMR chemical shifts are compared. The molecular structure of the 2-Benzylamino-5-methyl-5- propyl-2-oxo-1,3,2-dioxaphosphorinane (3d) has been determined by means of crystal Xray diffraction methods.

Keywords: Cyclophosphamide, diastereomeric 1, 3, 2-dioxaphosphorinane, NMR (31P, 1 H, 13C) analysis, DFT calculation, GIAO method, X-ray structure.

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[1]
Bentrude, W.G.; Hargis, J.H.D. Conformations of 6-membered-ring phosphorus hetrerocycles: the 5-t-butyl-2-oxo-1,3,2-dioxaphosphorinanes. J. Chem. Soc., 1969, 19, 1113-1114.
[2]
Bentrude, W.G.; Tan, H.W. Conformations of saturated cyclic phosphorus heterocycles II. 5-tert-butyl-2-amino-1,3,2-dioxaphosphorinanes apparent effects of P-N vicinal interactions on the conformational energy of amino groups on trivalent phosphorus and the influence of lone pair orientation. J. Chem. Soc., 1973, 95(14), 4666-4675.
[3]
Day, R.O.; Bentrude, W.G.; Yee, K.C.; Setzer, W.N.; Deiters, J.A.; Holmes, R.R. The first monocyclic 1,3,2-dioxaphosphorinane in a boat form: synthesis, structure and stability. J. Am. Chem. Soc., 1984, 106, 103-106.
[4]
Bajwa, G.S.; Chandrasekaran, S.; Hargis, J.H.; Sopchik, A.E.; Blatter, D.; Bentrude, W.G. Conformations of saturated six-membered ring phosphorus heterocycles. Cis- and trans-2-oxo- and 2-thio-2- (dimethylamino)-5-tert-butyl-1,3,2-oxazaphosphorinanes: Molecules related to cyclophosphamide. J. Am. Chem. Soc., 1982, 104, 6385-6392.
[5]
Setzer, W.N.; Sopchik, A.E.; Bentrude, W.G. Conformations of saturated six-membered-ring phosphorus heterocycles. Chair-chair equilibria for cyclophosphamide, the 5,5-dimethyl derivative, and related 1,3,2-oxazaphosphorinanes. J. Am. Chem. Soc., 1985, 107, 2083-2091.
[6]
Huang, Y.; Sopchik, A.E.; Arif, A.M.; Bentrude, W.G. X ray crystallographic study of 1,3,2-dioxaphosphorinane dimer containing five coordinated phosphorus in the 12 membered ring. Heteroatom Chem., 1993, 4, 271-278.
[7]
Hulst, R.; Zijlstra, R.W.J.; Vries, N.K.; Feringa, B.L. 4(S)-2H-2-oxo-5,5-dimethyl-4(R)-phenyl-1,3,2-dioxaphosphorinane, a new reagent for the enantiomeric excess determination of unprotected amino acids using 31P NMR. Tetrahedron Asymmetry, 1994, 5(9), 1701-1710.
[8]
Sartillo, P.F.; Sanchez, M.; Cruz, G.S.; Quinteroa, L. Conformational and configurational analysis of 2-phenoxy-2-oxo-1,3,2-dioxaphosphorinane. Conformational and configurational dependence upon conformation of the diol precursor. Tetrahedron, 2004, 60, 3001-3008.
[9]
Huang, Y.; Bentrude, W.G. Conformational equilibria of phosphorus with 5-alkyl-substituted 1,3,2-dioxaphosphorinane ring attached diequatorially to five coordinated phosphorus. J. Am. Chem. Soc., 1995, 117, 12390-12396.
[10]
Cholewinski, G.; Chojnacki, J.; Pikies, J.; Rachon, J. Synthesis and structural investigation of N-acyl selenophosphoramides. Org. Biomol. Chem., 2009, 7, 4095-4100.
[11]
Sun, Q.; Li, R.T.; Guo, W.; Cui, J.R.; Cheng, T.M.; Ge, Z.M. Novel class of cyclophosphamide prodrug: Cyclophosphamide spiropiperaziniums. Bioorg. Med. Chem. Lett., 2006, 16, 3727-3730.
[12]
Rudek, M.A.; Chau, C.H.; Figg, W.D.; McLeod, H.L. Handbook of anticancer pharmacokinetics and pharmacodynamics, 2nd ed; Springer Science of Business media: New York, 2014.
[13]
Krishnamurthy, S.; Sreenivasa, R.V.; Nethagi, M. Phosphorus-Nitrogen heterocycles as ligands in organometallic chemistry. Phosphorus Sulfur Silicon Relat. Elem., 1992, 64, 99-106.
[14]
Ostergaard, M.E.; Gerland, B.; Escudier, J-M.; Swayze, E.E.; Seth, P.P. Differential effects on allele selective silencing of mutant huntingtin by two stereoisomers Of α, β-Constrained nucleic acid. ACS Chem. Biol., 2014, 9, 1975-1979.
[15]
Martinez, O.; Ecochard, V.; Mahéo, S.; Gross, G.; Bodin, P.; Teissié, J.; Escudier, J-M.; Paquereau, L. α, β -D-Constrained nucleic acids are strong terminators of thermostable DNA polymerases in polymerase chain reaction. Plos One., 2011, 6(10), e 25510..
[16]
Perry, M.C. The Chemotherapy Source Book, 5th ed; Williams and Wilkins: Baltimore, 1992.
[17]
Dorr, R.T.; Von-Hoff, D.D. Drug Monographs. Cancer Chemotherapy Handbook; 2nd Ed: Connecticut,, 1994.
[18]
Gholivand, K.; Dorosti, N.; Shariatinia, Z.; Ghaziany, F.; Sarikhani, S.; Mirshahi, M. Cyclophosphamides analogues: synthesis, spectroscopic study and antitumor activity of diazaphosphorinanes. Med. Chem. Res., 2011, 20, 1287-1293.
[19]
Ben Akacha, A.; Ayed, N.; Baccar, B. Phospho-4-pyrazoles. Synthèse et étude spectrographique RMN 1H,31P et 13C. Phosphorus Sulfur Silicon Relat. Elem., 1988, 40, 63-68.
[20]
Boukraa, M.; Ayed, N.; Ben Akacha, A.; Zantour, H.; Baccar, B. Action du réactif de lawesson sur les hydrazones β-phosphonatées: Synthèse de (5-méthylène-Phosphine oxyde)-3- thioxo-1,3,2-diazaphospholines. Phosphorus Sulfur Silicon Relat. Elem., 1995, 105, 17-21.
[21]
Ben Akacha, A.; Barkallah, S.; Zantour, H. 13C NMR and 31P NMR spectral assignment of new β-phosphonylated hydrazones. Magn. Reson. Chem., 1999, 37(12), 916-920.
[22]
Kanzari-Mnallah, D.; Efrit, M.L.; Ben Akacha, A. Synthèse de 1,3,2-dioxaphosphorinanes diastereoisomeres: Influence de la conformation des 1,3-diols de départ sur leurs structures et conformations. Phosphorus Sulfur Silicone Relat. Elem., 2017, 192(6), 665-673.
[23]
Salah, N.; Arfaoui, Y.; Bahri, M.; Efrit, M.L.; Ben Akacha, A. Synthèse et étude conformationnelle par RMN (1H,13C,31P) et DFT des Cycloalcoxyphosphinallenes et des hydrazones β-Cycloalcoxyphosphonatees. Phosphorus Sulfur Silicon Relat. Elem., 2013, 188, 609-622.
[24]
Lucas, H.J.; Mitchell, F.W.; Scully, C.N. Cyclic phosphites of some aliphatic glycols. J. Am. Chem. Soc., 1950, 72, 5491-5497.
[25]
Ben Akacha, A. Les hydrazones phosphorées: Préparation, structure et intermédiaires de synthèse hétérocyclique. PhD Thesis, Faculty of science of Tunis: Tunis, April, 1987.
[26]
Verkade, J.G.; Quin, L.D. Phosphorus-31 NMR spectroscopy in stereochemical analysis. Magn. Reson. Chem., 1988, 26, 178.
[27]
Keglevich, G. Phosphine chalcogenides. In: Organophosphorus Chemistry; Allen, D.W.; Loakes, D.; Tebby, J.C., Eds.; Royal Society of Chemistry: UK, 2016; Vol. 45, pp. 99-131.
[28]
Burla, M.C.; Camalli, M.; Carrozzini, B.; Cascarano, G.L.; Giacovazzo, C.; Polidori, G.; Spagna, R. Sir99: A program for the automatic solution of small and large crystal structures. Acta Crystallogr. A, 1999, 55, 991-999.
[29]
Sheldrick, G.M. A short history of shelx. Acta Crystallogr. A, 2008, 64, 112-122.
[30]
Spek, A.L. Platon98: A multipurpose cystallographic tool; Utrecht University: The Netherlands, 1998.
[31]
Farrugia, L.J. Wingx suite for small-molecule single-crystal crystallography. J. Appl. Cryst., 1999, 32, 837-838.
[32]
Wilson, A.J.C. International Tables for X-ray Crystallography, Volume C: Mathematical,Physical and Chemical Tablese ; ed. Kluwer Academic Press: Boston, 1992.
[33]
Brandenburg, K. Diamond 3.0; Crystal Impact GbR: Bonn, Germany, 2008.
[34]
Frisch, M.J.; Trucks, G.W.; Schlegel, H.B.; Scuseria, G.E.; Robb, M.A.; Cheeseman, J.R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G.A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H.P.; Izmaylov, A.F.; Bloino, J.; Zheng, G.; Sonnenberg, J.L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J.A.; Peralta, J.E.; Ogliaro, F.; Bearpark, M.; Heyd, J.J.; Brothers, E.; Kudin, K.N.; Staroverov, V.N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J.C.; Iyengar, S.S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J.M.; Klene, M.; Knox, J.E.; Cross, J.B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R.E.; Yazyev, O.; Austin, A.J.; Cammi, R.; Pomelli, C.; Ochterski, J.W.; Martin, R.L.; Morokuma, K.; Zakrzewski, V.G.; Voth, G.A.; Salvador, P.; Dannenberg, J.J.; Dapprich, S.; Daniels, A.D.; Farkas, Ö.; Foresman, J.B.; Ortiz, J.V.; Cioslowski, J.; Fox, D.J. Gaussian 09, Revision D.01; Gaussian, Inc.: Wallingford, CT, 2009.
[35]
Becke, A.D. Density-Functional Thermochemstry. The role of exact exchange. J. Chem. Phys., 1993, 98, 1372-1377.
[36]
Ditchfield, R. Self-consistent perturbation theory of diamagnetism: Gauge-invariant lcao method for NMR chemical shifts. Mol. Phys., 1974, 27, 789-807.
[37]
Wolinsky, K.; Hilton, J.F.; Pulay, P. Efficient implementation of the gauge independent atomic orbital method for NMR chemical shift calculations. J. Am. Chem. Soc., 1990, 112, 8251-8260.
[38]
Cheeseman, J.R.; Tucks, G.W.; Keith, T.A.; Frisck, M.J. A comparison of models for calculating nuclear magnetic resonance shielding tensors. J. Chem. Phys., 1996, 104, 5497-5509.
[39]
Tait, K.M.; Parkinson, J.A.; Jones, A.C.; Ebenezer, W.J.; Bates, S.P. Comparison of experimental and calculated 1H NMR chemical shifts of geometric photoisomers of azodyes. Chem. Phys. Lett., 2003, 374, 372-380.
[40]
Munoz, M.A.; Nathan, P.J. DFT-GIAO 1H and 13C NMR prediction of chemical shifts for the configurational assignement of 6β-hydroxyhyoscy-amine diastereoisomers. Magn. Reson. Chem., 2009, 47, 578-584.

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