Synthesis and design of isatogens of potential biological interest
The synthesis, including the preparation of the
intennediate acetylenes, indolines and benzoin oximes, the
reactions and biological properties of isatogens are
A detailed study is made of the preparation of 2-substituted
indolines, from indoles, and 2-substituted-I-hydroxyindoles,
from benzoin derivatives, and their subsequent
oxidation to isatogens with 3-chloroperbenzoic acid. In
particular the mechanisms, limitations and scope of these
methods have been investigated. The most versatile method
for the synthesis of isatogens is confinned as that
proceeding via the intermediate tolans. The preparation of
a variety of terminal acetylenes is described, in particular
2-,3-, and 4-ethynylpyridines are prepared in higher yields
than previously reported. The acetylenes were coupled with
a variety of 2-nitrohalogenoaryl compounds using bis(triphenylphosphine)
palladium(II) chloride to give a variety of
novel tolans including those derived from ethynylphenylsulphide.
The steric and electronic limitations of these
reactions are discussed.
Cyclisation of the tolans gave a variety of novel isatogens
including 2-phenyl and 2-pyridyl, 4, 5, 6, and 7-
substituted, isatogens and a number of 2-thiophenylisatogens.
The latter are the first isatogens to be described with a
heteroatom at the 2-position. The analogous reaction with
phenoxyacetylene failed to yield the isatogen. The importance
of steric and electronic factors and scope of all these
reactions is discussed.
1 13 The mass spectra, Hand C nmr spectra are discussed
for a number of indolines and isatogens. An interesting
upfield shift of the 3-methyl signal in 2,3 trans di- and
3,3,3-trimethylindoline tosylates is described.
The activity of the isatogens in three different
biological systems, a) ATP antagonism, b) muscle relaxation,
and c) inhibition of mitochondrial respiration is described
and a preliminary attempt is made to relate activity with a
variety of physico-chemical parameters; new isatogens, with
novel structures, are proposed which would be predicted to
be more potent and more selective in their biological actions.