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An alternate synthesis, x‐ray crystal structure and p388 activity of 1,2‐bis(dibenzophospholyl‐1)ethane
Author(s) -
Sutton Blaine M.,
Girard Gerald R.,
Eggleston Drake S.,
Baures Paul W.,
Faucette Leo F.,
Johnson Randall K.,
Hill David T.
Publication year - 1990
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570270459
Subject(s) - chemistry , reagent , yield (engineering) , crystal structure , metal , medicinal chemistry , metalation , x ray , lithium (medication) , ligand (biochemistry) , molecule , stereochemistry , crystallography , organic chemistry , receptor , medicine , biochemistry , metallurgy , endocrinology , physics , quantum mechanics , materials science
Synthesis of 1,2‐bis(dibenzophospholyl‐l)ethane ( 2 ) in 45% yield was accomplished in a single step via the coupling of 2,2′‐dilithiobiphenyl with 1,2‐bis(dichlorophosphino)ethane. The dilithio reagent was generated in situ by the metalation of 2,2′‐dibromobiphenyl with n‐butyl lithium. The 31 P[ 1 H] nmr chemical shift of 2 at δ 11.2 ppm (deuteriochloroform) is slightly upfield from the δ 12.8 ppm observed for 1,2‐bis(diphenylphosphino)ethane, the nonconstrained analog 1 , relative to external trimethyl phosphate (δ 31 P 2.0 ppm). X‐ray crystallography showed 2 crystallized in space group P2 1 /c with lattice constants a = 5.752(1) Å, b = 12.891(2) Å, c = 13.675(3) Å and β = 100.74(2)° with Z = 2. Compound 2 formed a bis[chlorogold(I)] complex in a fashion similar to the known metal complexing ligand 1 . Evaluation of 2 in an ip P388 leukemia mouse model resulted in an increased life span (ILS) of 70% relative to controls, at a maximally tolerated dose (MTD) of 20.2 μmol/kg. By comparison 1 afforded an ILS of 100% at an MTD of 40 μmol/kg.