Intermediates for the production of picropodophyllin and related

Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...

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560 56, 564158, 568312, 568327, C07D31744, C07C 6976

Patent

active

043919820

ABSTRACT:
The present invention provides compounds having the structure: ##STR1## wherein R.sup.1 represents alkoxy or aralkoxy, R.sup.2 represents hydrogen, alkoxy, aralkoxy, alkyl, aralkyl, or R.sup.1 and R.sup.2 taken together represent the group --O--CH.sub.2 --O--, R.sup.3 represents hydrogen, alkyl, aralkyl, acyl or a protecting group, Y represents Cl, Br, I or a leaving group; and X represents Cl, Br or I.
The present invention also provides a process for preparation of compounds VI in a single step wherein X and Y are the same and represent Cl, Br, ,or I, and R.sup.3 is as previously defined except that in this instance, it does not represent a protecting group.
According to another aspect of the present invention there are provided compounds VII-a and VII-b having the structure: ##STR2## wherein R.sup.1, R.sup.2 and R.sup.3 are as previously defined, j is an integer having a value of 0 or 1, Z.sup.1 represents a non-reacting electron withdrawing group, and Z.sup.2 represents a non-reacting electron withdrawing group or hydrogen, R.sup.8 and R.sup.9 are the same or different and represent hydrogen, alkyl, aralkyl, alkoxy, or aralkoxy, and R.sup.7 represents hydrogen, alkyl, aralkyl or acyl. Compounds VII-a may be prepared from compounds VI through the use of the process of "insertion-cyclization" which is provided by another aspect of the present invention.
According to a further aspect of the present invention, compounds VII-a are converted into tetralone III-a shown below: ##STR3## wherein R.sup.1, R.sup.2, R.sup.3, Z.sup.1, Z.sup.2, R.sup.7, R.sup.8 and R.sup.9 are as previously defined. Certain of these compounds can, in turn, be readily converted into picropodophyllin and picrosikkimotoxin. The latter can be converted into known antineoplastic agents by known procedures.

REFERENCES:
patent: 2507473 (1950-05-01), Koelsch
patent: 2658910 (1953-11-01), Johnson et al.
Gensler et al, Journ. Amer. Chem. Society, vol. 82, pp. 1714-1727, (1960).

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