Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1996-04-04
1997-11-04
Owens, Amelia
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
C07D30702
Patent
active
056841663
DESCRIPTION:
BRIEF SUMMARY
This invention relates to novel compounds, methods of their preparation and medical uses thereof.
Although there have been many proposals for dealing with cellular malfunction e.g. in conditions embraced by the general term "cancer", these have usually involved surgery supplemented by a treatment e.g. chemo- or radiotherapy, which also causes some undesirable side effects such as hair loss, suppression of the immune system or other toxic effects. Thus in many cases, a patient's health can suffer significantly as a result of the treatment. There is an ever increasing need to find physiologically acceptable low-toxicity agents for use in medicine.
In other areas, post injury or surgery tissue regrowth may be unsatisfactory with excessive formation of scar tissue. A means of regulating the growth of tissue to minimise scar tissue formation would be desirable.
An object of the present invention is to obviate or mitigate the aforesaid disadvantages by providing compounds which have beneficial physiological effects and cell growth regulatory function.
According to this invention there are provided compounds of the formula (Ia) in which the compound normally exists as a keto-enol tautomeric pair, the racemic keto form of which is represented by the formula ##STR2## wherein R is a hydrogen, lower alkyl, acyl, or another functional group of up to 6 carbons including at least one hetero atom, which atom may be directly bonded to the .beta.-carbon, which compound may be in the acyclic form shown or in a cyclic form as equilibrium keto-enol tautomer derivatives and anomeric forms thereof, including enantiomers when R is hydrogen and diastereoisomers when R is another group. Thus the group may be hydroxyl, a primary or secondary amine, amide, an acyl group, sulphur containing group etc.
Such formula (Ia) compounds are obtainable by a synthesis method be particularly described hereinafter with reference to the preferred compound which exists as a keto-enol tautomeric pair, the racemic keto form being of formula Ia where R.dbd.H i.e. (3-ketotetrahydrofuran-2-yl)ethanal and whilst not wishing to be bound by any theory, the attached scheme illustrates the equilibrium or molecular rearrangement relationships established between compounds of the invention (wherein R.dbd.H). However it must be emphasised that there may be parallel contributory intermediates or reaction steps not specifically identified in such an illustrative scheme. It will be appreciated that when R is hydrogen then various enantiomers are available but when R is not hydrogen a diastereomeric relationship is apparent between certain pairs of the compounds shown.
According to the invention compounds of therapeutic value are obtainable for example by subjecting trans-hexen-3-ene-1,6-diol to an iodo-etherification reaction to give the corresponding 3-iodotetrahydrofuran which retains the free .alpha.-hydroxyl which must be protected for subsequent reaction to displace the iodine yielding the cis 3-hydroxytetrahydrofuran which upon deprotection and Swern oxidation provides the desired racemic (3-ketotetrahydrofuran-2-yl)ethanal.
The same compounds can be derived by starting from an appropriate dihydrofuran having a protected primary alcohol side chain in the 2-position. Thus one route to these therapeutically active compounds is to subject the said protected alcohol side chain-substituted dihydrofuran to oxidation using a chromium-based reagent to yield the corresponding acid which in turn is subjected to iodolactonisation conditions to yield the cis, cis, trans-trisubstituted iodo-lactone which upon displacement of the iodine provides the cis, cis, cis-tri-substituted hydroxy-lactone capable of being reduced to obtain a lactol which is in equilibrium with the corresponding open chain aldehyde.
In this invention it is preferred that the .alpha.-hydroxyl is protected using a lipophilic tri-hydrocarbylsilyl derivative, e.g. using triisopropylsilyl chloride as reagent.
The invention will now be illustrated by way of example but it will be understood by those in th
REFERENCES:
Rearrangement of Oxonium Ylides," J. Am. Chem. Soc. 1986,108, 6060-6042.
Biocure Limited
Owens Amelia
LandOfFree
(-3-ketotetrahydrofuran-2-yl) ethanal derivatives and a method f does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with (-3-ketotetrahydrofuran-2-yl) ethanal derivatives and a method f, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and (-3-ketotetrahydrofuran-2-yl) ethanal derivatives and a method f will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1834198