Cyclophosphamide and its congeners

Hutchinson, D. W.; Miller, J. A.; Stec, Wojciech J.

doi:10.1039/9781847554338-00145

Cited by 45 publications

(27 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The changes in H-9, H-10 chemical shifts for 5 us. 4 are paralleled by similar changes for H-8, H-9 in 7 us. 6.…”

mentioning

confidence: 71%

“…19 Similarly, any significant chair l-chair 2 equilibration would tend ito average the 3J(P,H) for axial and equatorial protons and reduce their difference. l o Since H-loa in 4 and H-9a in 6 also have large 3J( P, H) values, a trans dihedral angle to phosphorus is again implied. Taking ali this information into account lea& to the conclusion that 4 and 6 have a cis (rel-lR,61P) ring junction as shown in Scheme 2.…”

Section: Amentioning

confidence: 97%

“…Finally, the angles predicted by ALCHEMY and A M l for the thiazolidine ring protons agree weil with rhe observed changes in the couplings for H-8, H-9 in 6 us. 4 (large a-e and e-a couplings, small e-e coupling). The five-membered ring adopts an envelope conformation with N-1 out of the plane, H-8a endo and H-9a exo.…”

Section: Ring 2 Planarmentioning

confidence: 98%

“…4.O]decanes 4 and 5 (see Scheme 1 and Experimental). Equal amounts of the diastereomeric l-aza-2-bis(2-chloroethyl)amino-3-oxa-2-oxo-2-phospha-7-thia-bicyclo[4.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Use of two‐dimensional NMR and molecular modelling for the structure determination of novel cyclophosphamide derivatives: Diastereomers of 1‐aza‐2‐bis(2‐chloroethyl)‐ amino‐3‐oxa‐2‐oxo‐2‐phospha‐7‐thia‐bicyclo‐ [4.4.0]decane and [4.3.0]nonane

Schmidt

Tang

Eisenbrand

et al. 1992

Magnetic Reson in Chemistry

View full text Add to dashboard Cite

High-field NMR studies at 11.7 T of newly synthesized diastereomeric l-aza-2-bis(2-chlorothyl)amino-3-oxa-2-oxo-2-phospha-7-thia-bicyclo[ 4.4.01 decanes (4, 5) and the corresponding [ 4.3.01 nonanes (6, 7) were carried out by employing a combination of one-and two-dimensional horno-and heteronuclear methods. Unarnbiguous 31P, 'H and ' 3C chemical shift assignments for these bicyclic derivatives of cyclophosphamide were obtained, and the spin-spin couplings involving 'H, I3C and "P were analysed in detail to determine the stereochemistry. Particularly useful were 'H J-resolved experiments, which separated phosphorusproton couplings from proton-proton couplings, and 'H-"C shift-correlation experiments, which resolved the carbowphosphorus couplings and provided information on the relative signs of J(P,H) and J(P,C). In addition, extensive molecular modelling calculations using various force-field (ALCHEMY, DISCOVER) and molecular orbital methods (MNDO, AM1, PM3) were carried out, and improved parameters for cyclophosphamides were developed for ALCHEMY. The diastereomeric pairs 4, 5 and 6, 7 differ in the axial YS. equatorial orientation of the sulphur substituent on the oxazaphosphorinane ring, which is itself exclusively in a chair conformation with axial P-O for al1 substances.

show abstract

“…The changes in H-9, H-10 chemical shifts for 5 us. 4 are paralleled by similar changes for H-8, H-9 in 7 us. 6.…”

mentioning

confidence: 71%

Section: Amentioning

confidence: 97%

Section: Ring 2 Planarmentioning

confidence: 98%

“…4.O]decanes 4 and 5 (see Scheme 1 and Experimental). Equal amounts of the diastereomeric l-aza-2-bis(2-chloroethyl)amino-3-oxa-2-oxo-2-phospha-7-thia-bicyclo[4.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Use of two‐dimensional NMR and molecular modelling for the structure determination of novel cyclophosphamide derivatives: Diastereomers of 1‐aza‐2‐bis(2‐chloroethyl)‐ amino‐3‐oxa‐2‐oxo‐2‐phospha‐7‐thia‐bicyclo‐ [4.4.0]decane and [4.3.0]nonane

Schmidt

Tang

Eisenbrand

et al. 1992

Magnetic Reson in Chemistry

View full text Add to dashboard Cite

show abstract

“…2 It is known that condensation products of phosphorylacetic acid and amino acids, e.g., with aspartic acid (PALA preparation), are strong carcino lytics 3 and the corresponding hydrazides exhibit anti amnestic, antihypoxic, and antidepressant activities. 4 In connection with this, it was of interest to synthesize a series of 1,3,2 oxazaphosphinane analogs of these and some structurally related compounds.…”

mentioning

confidence: 99%

1,3,2-Oxazaphosphinane analogs of phosphorylacetic acid derivatives: synthesis and properties

et al. 2005

View full text Add to dashboard Cite

Reactions of 2 AlkO 1,3,2 oxazaphosphinanes with alkyl N haloacetylamino or N chloro methyl N methoxycarbonylamino carboxylates mainly give products with retention (Alk = Me) and opening of the ring (Alk = Et). In aqueous solution, cyclic products with the N isopropyl group are only stable, while the rest undergo hydrolysis with cleavage of the P-N bond of the ring. Oxazaphosphinane analogs of phosphorylacetamide and phosphorylacetohydrazide were synthesized.Key words: 2 alkoxy 1,3,2 oxazaphosphinanes, 2 alkoxy 3 alkyl 1,3,2 oxazaphosphinanes, the Arbuzov rearrangement, alkyl haloacetylamino carboxylates, N chloromethyl N methoxy carbonylglycine methyl ester, N [(2 oxo 1,3,2λ 5 oxazaphosphinan 2 yl)acetyl]glycine methyl ester, hydrolysis, alkyl N [(3 alkyl 2 oxo 1,3,2λ 5 oxazaphosphinan 2 yl)acetyl]amino carboxy lates, N {[(3 bromopropylamino)ethoxyphosphoryl]acetyl}glycine methyl ester, N [(3 isopro pyl 2 oxo 1,3,2λ 5 oxazaphosphinan 2 yl)methyl] N methoxycarbonylglycine methyl ester,Earlier, 1 we have described synthesis of 1,3,2 oxaza phosphinane analogs of phosphorylacetates with poten tial biological activity, in which, by analogy with carcino lytic cyclophosphamide, the oxazaphosphinane ring plays the role of a "carrier" of a pharmacophoric group to a cell through cell membranes. 2 It is known that condensation products of phosphorylacetic acid and amino acids, e.g., with aspartic acid (PALA preparation), are strong carcino lytics 3 and the corresponding hydrazides exhibit anti amnestic, antihypoxic, and antidepressant activities. 4 In connection with this, it was of interest to synthesize a series of 1,3,2 oxazaphosphinane analogs of these and some structurally related compounds.1,3,2 Oxazaphosphinane analogs of phosphorylacetic acid containing fragments of amino acid esters were syn thesized by the Arbuzov reaction described in detail for the reactions of 2 alkoxy 3 alkyl 1,3,2 oxazaphosphin anes (1) with bromoacetates. 1 In the present work, com pounds 1 reacted with alkyl N haloacetylamino carboxy lates (2) (Scheme 1).Reactions with N bromoacetyl derivatives were car ried out in benzene at 20-50 °C, while those with N chloroacetyl derivatives, in toluene at 100-110 °C. As with bromoacetates, 1 the reactions gave cyclic (3) and acyclic products (4). According to 31 P NMR data, their ratio is virtually independent of the nature of the substitu ent R 1 at the N atom in oxazaphosphinanes 1 but is deter mined by the substituent R 2 in the alkoxy group (Table 1). For instance, for R 2 = Me, cyclic products are dominant (the ratio 3 : 4 varies from 93 : 7 to 86 : 14), while for R 2 = Et, the major product is an acyclic one (3 : 4 = 25 : 75)*. For pairs of compounds 3f, 4g and 3g, 4h, the 31 P NMR spectra in benzene show doubled signals due to diastereomeric anisochronism.The use of oxazaphosphinane 1d in the Arbuzov reac tion with N chloromethyl N methoxycarbonylglycine methyl ester (5) (Scheme 2) afforded cyclic (6) and acy clic products (7) in the 82 : 18 ratio ( 31 P NMR).In this case, the 31 P NMR spectrum...

show abstract

Bis-(2-chloroethyl)phosphoramidic Dichloride

Sieck

Hanson

2003

Encyclopedia of Reagents for Organic Synthesis

View full text Add to dashboard Cite

Cyclophosphamide and its congeners

Cited by 45 publications

References 0 publications

Use of two‐dimensional NMR and molecular modelling for the structure determination of novel cyclophosphamide derivatives: Diastereomers of 1‐aza‐2‐bis(2‐chloroethyl)‐ amino‐3‐oxa‐2‐oxo‐2‐phospha‐7‐thia‐bicyclo‐ [4.4.0]decane and [4.3.0]nonane

Use of two‐dimensional NMR and molecular modelling for the structure determination of novel cyclophosphamide derivatives: Diastereomers of 1‐aza‐2‐bis(2‐chloroethyl)‐ amino‐3‐oxa‐2‐oxo‐2‐phospha‐7‐thia‐bicyclo‐ [4.4.0]decane and [4.3.0]nonane

1,3,2-Oxazaphosphinane analogs of phosphorylacetic acid derivatives: synthesis and properties

Bis-(2-chloroethyl)phosphoramidic Dichloride

Contact Info

Product

Resources

About