Hexamethylene Chain Research Articles

ChemInform Abstract: (6)METACYCLOPHANE AND RELATED COMPOUNDS

AbstractDas aus Cyclooctanon durch Kondensation mit Bemsteinsäurediäthylester und Behandlung mit Polyphosphorsäure und Bromwasserstoff hergestellte Cyclopentenon (I) wird mit Lithiumaluminiumhydrid zu dem Alkohol (II) reduziert.

6]METACYCLOPHANE AND RELATED COMPOUNDS

Abstract The title phane (IV) with the shortest aliphatic bridge among [n]metacyclophanes has been obtained from the enone I. The PMR spectra indicate the pseudorotation of the hexamethylene chain occurring with abnormally high energy barrier of 11.1 kcal/mol at −31.5°C for IV and 12.4 kcal/mol at −4.5°C for its 12-bromo derivative (III).

Synthesis and Pharmacological Studies of Some Aliphatic Hemicholinium Analogs

The aromatic nucleus of hemicholinium-3 was replaced with an aliphatic hexamethylene chain without loss of the characteristic pharmacological activity. The toxic dose was elevated in mice about tenfold by the change. Choline chloride was a very effective antidote to intoxication from the aliphatic hemicholinium. Another compound synthesized, a pyridine analog, had marked anticholinesterase activity, but caused a flaccid paralysis in avian musculature. A third compound, a trimethylamine analog, elicited neuromuscular blockade typical of decamethonium.

Tumour-inhibiting action of 1 : 6-dimethanesulphonyl-D-mannitol.

EXTENSIVE clinical experience with ‘Myleran’ (I, n= 4) in the treatment of chronic myeloid leukaemia1 has shown that when over-dosage is avoided the drug is free from side-effects. On the other hand, other alkylating agents which are used clinically, namely, ethyleneimine derivatives and nitrogen mustards, usually cause some side-effects. This contrast may be attributable to a different mechanism of action for ‘Myleran’ and for the other alkylating agents. Evidence for this difference arises from comparison of the effects of ‘Myleran’ and a mustard (chlorambucil) on rat bone-marrow2 and from a similar comparison where, when the drugs were used clinically in leukaemia, there was no enhanced excretion of uric acid after administration of ‘Myleran’ although nitrogen mustards and tri-ethylenemelamine caused a significant rise in uric acid excretion3. ‘Myleran’ and its congeners (I), while they inhibit experimental tumours, cause a marked depression of bone-marrow function and cannot therefore be considered suitable for the treatment of solid tumours in man. In the ‘Myleran’ series there is evidence that variations in neutrophil-depressing and also in tumour-inhibitory activity may depend very much on the ratio between the solubility of the particular compound in water and in ether4. In the hope that a very large relative increase in water solubility might possibly minimize the bone-marrow depressing properties of the ‘Myleran’ series while leaving unaffected tumour-inhibitory activity together with the apparent clinical virtues attributable to the ‘Myleran’ type of action, we decided to modify the series by the insertion of hydroxy groups in the polymethylene chain. Bis-l :6-2′-chloroethylamino-1:6-dideoxy-D-mannitol (II) had been made because it was a type of nitrogen mustard which it was thought might inhibit glycolysis5. The fact that its tetrahydroxylated hexamethylene chain structure was consistent with tumour-inhibiting activity led us to choose 1 : 6-dimethanesulphonyl-D-mannitol (III) as the first member of our new series.

Amide bands in infra-red spectra: the direction of the transition moments of bands in N,N' -diacetylhexamethylenediamine

Results of crystallographic structural analysis are briefly summarized, and are used in conjunction with infra-red dichroic measurements to ascertain the direction within the molecule of the transition moments of infra-red bands. Bands affected by deuteration of the amide groups are assigned to vibrations of the 'amide’ portion of the molecule, and those unaffected by deuteration are assigned to vibrations of the hexamethylene chain and methyl groups. In a few cases the origin of a band is disclosed by the direction of its transition moment.