A method of preparation of intermediates for the production of picropodophyllin.

摘要

The present invention provides compounds having the structure: IMAGE VI wherein R1 represents alkoxy or aralkoxy, R2 represents hydrogen, alkoxy, aralkoxy, alkyl, aralkyl, or R1 and R2 taken together represent the group -O-CH2-O-, R3 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 R3 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: IMAGE wherein R1, R2 and R3 are as previously defined, j is an integer having a value of 0 or 1, Z1 represents a non-reacting electron withdrawing group, and Z2 represents a non-reacting electron withdrawing group or hydrogen, R8 and R9 are the same or different and represent hydrogen, alkyl, aralkyl, alkoxy, or aralkoxy, and R7 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: IMAGE III-a wherein R1, R2, R3, Z1, Z2, R7, R8 and R9 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.