Organic compounds -- part of the class 532-570 series – Organic compounds – Cyclopentanohydrophenanthrene ring system containing
Patent
1993-01-11
1995-02-21
Dees, Jose G.
Organic compounds -- part of the class 532-570 series
Organic compounds
Cyclopentanohydrophenanthrene ring system containing
552625, 552643, C07C 4565
Patent
active
053917782
DESCRIPTION:
BRIEF SUMMARY
This invention relates to new intermediate products of general formula I ##STR2## in which R.sup.1 stands for a hydrogen atom or a straight-chain or branched alkyl group with 1 to 4 carbon atoms, radical or else
A hydrogen atom or a methyl group is preferred for R.sup.1.
As acyloxy group R.sup.4, first of all the acetoxy group is suitable.
This invention especially relates to the following compounds:
The intermediate products of general formula I are suitable in an excellent way for introducing a .DELTA..sup.1 double bond in the steroid skeleton with the simultaneous presence of a .DELTA..sup.4 double bond as well as saturated carbonyl groups.
Reaction of a compound of general formula I with a base in an amidic solvent at elevated temperature with cleavage of hydrogen iodide results in a compound of general formula II ##STR3## in which R.sup.1, R.sup.2, R.sup.3 and R.sup.4 have the meaning indicated in formula I.
If R.sup.2 stands for a hydrogen atom, after the hydrogen iodide cleavage, the A-ring aromatizes with the formation of a compound of general formula II' ##STR4##
This invention further relates to a process for the production of new intermediate products of general formula I.
In this connection, either a compound of general formula III ##STR5## in which R.sup.5 means an acyl or trialkylsilyl group with up to 10 carbon atoms in the group (EP-A 0290378; DE-A 3 715 869), is reacted with N-iodosuccinimide, optionally generated in situ, in a solvent, for example in an alcohol such as methanol, ethanol, propanol or the like to the compound of general formula Ia ##STR6## or with iodomonochloride or iodomonobromide in an aprotic solvent in the presence of a base or with elementary iodine in acetic acid by adding a base to the compound of formula Ib ##STR7## or a compound of general formula IV ##STR8## in which R.sup.1, R.sup.2, R.sup.3 and R.sup.4 have the meaning indicated in formula I, N-iodosuccinimide or an N-iodamide, such as 1,3-diiodo-5,5-dimethylhydantoin or another N-iodimide in the presence of an equimolar amount of a copper compound in acetic acid or in an inert solvent, e.g., in an ether such as THF, by adding a catalytic amount of acetic acid or another C.sub.1 -C.sub.3 carboxylic acid to a compound of general formula Ic ##STR9##
By selecting the reaction conditions, the stereochemistry of the iodization reaction can thus be controlled, namely so that either the 2.alpha.-form Ia, the 2.beta.-form Ib or a 2.alpha./2.beta. mixture can be produced. Regioselective iodizations on 3,17-diketo steroids are new, as is the already mentioned .DELTA..sup.1 -introduction on 1-alkyl-substituted steroids by hydrogen iodide cleavage. The reaction in the allyl position frequently occurring in brominations (see the literature indicated on p. 6: C. Djerassi; A. Corbellini) is not observed in the iodization.
Similar compounds with 2-iodo-3-keto-.DELTA..sup.4 structure (without 1-alkyl substituent) are already known, but have been produced in low yield from the corresponding bromine compound by halogen exchange with sodium iodide [J. Am. Chem. Soc. 72, 4077, (1962)].
Advantageous embodiments of the process for the production of compounds of general formula I follow from subclaims 4 to 10.
The reaction of the compounds of general formula III with N-iodosuccinimide is preferably performed in an alcohol such as methanol, ethanol, propanol or 2-propanol. The reaction takes place with N-iodosuccinimide generated in situ, best of all in acetone or methanol.
As solvent for the iodization of the compounds of general formula III or IV with iodomonochloride or iodomonobromide, ethers such as tetrahydrofuran or ketones such as, for example, acetone or methyl isobutyl ketone, have proven especially suitable.
The iodization of compounds of general formula III with elementary iodine is performed preferably of all in glacial acetic acid as solvent.
As a base for iodization with iodomonochloride, iodomonobromide or with elementary iodine, especially a carboxylic acid salt such as sodium acetate or the like or an amine such as, f
REFERENCES:
patent: 3546259 (1970-12-01), Boswell, Jr. et al.
patent: 3775404 (1973-11-01), Buzby, Jr. et al.
patent: 4311646 (1982-01-01), Nitta et al.
patent: 4871482 (1989-10-01), Nickisch et al.
Brodie et al., "Steroids", 6:6, Dec. 1965, pp. 659-674.
Shaw et al., "Journal of Medicinal Chemistry", 7:4, Jul. 1964, pp. 555-560.
Berkoz et al., "Journal of Organic Chemistry", 28:8, Aug. 1963, pp. 1976-1982.
Harre Michael
Nickisch Klaus
Rohde Ralph
Westermann Jurgen
Dees Jos,e G.
Frazier B.
Schering Aktiengesellschaft
LandOfFree
2-iodo-3-keto-.DELTA..sup.4 steroids, process for their producti does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with 2-iodo-3-keto-.DELTA..sup.4 steroids, process for their producti, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and 2-iodo-3-keto-.DELTA..sup.4 steroids, process for their producti will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1931566