Cytotoxic bicyclo[7.3.1]tridec-4-ene-2,6-diyne compounds and process for the preparation thereof
AssigneeBristol-Myers Squibb Company
InventorsJohn F. Kadow, Mark D. Wittman
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Abstract
The present invention relates to a novel and efficient process for the preparation of 8-hydroxybicyclo[7.3.1]tridec-4-ene-2,6-diyne ring system which is part of the aglycone of esperemicin and to novel cytotoxic antitumor agents having said bicyclic ring system. The present invention also provides a method for treating mammalian malignant tumors by administering to an animal in need of such treatment an antitumor effective amount of a compound of the present invention.
Claims5
A process for preparing a compound having the formula
- wherein
- R.sup.1 is hydroxy protecting group;
- R.sup.2 is H or protected hydroxy;
- R.sup.3 and R.sup.4 are independently H or protected hydroxy, or R.sup.3 and R.sup.4 taken together represent a protected keto group;
- and
- R.sup.5 is C.sub.1-5 alkyl, C.sub.3-6 cycloalkyl, C.sub.6-10 aryl, or C.sub.6-10 aryl substituted with one or more groups selected from C.sub.1-5 alkyl and C.sub.1-5 alkoxy, which comprises the steps of:
- a) reacting a compound having the formula ##STR39## with a compound having the formula
- R.sup.5 --S--Al(R.sup.6).sub.2
- wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, and R.sup.5 are as defined above and R.sup.6 is C.sub.1-5 alkyl;
- and
- b) reacting the product of step a with a reagent selected from Ti[O--(C.sub.1-5)alkyl].sub.4 and XTi[O--(C.sub.1-5)alkyl].sub.3, wherein X is halogen.
A compound having the formula ##STR40## wherein R.sup.1 is hydroxy protecting group;
- R.sup.2 is H or protected hydroxy;
- R.sup.3 and R.sup.4 are independently H or protected hydroxy, or R.sup.3 and R.sup.4 taken together represent a protected keto group;
- and
- R.sup.5 is C.sub.1-5 alkyl, C.sub.3-6 cycloalkyl, C.sub.6-10 aryl, or C.sub.6-10 aryl substituted with one or more groups selected from C.sub.1-5 alkyl and C.sub.1-5 alkoxy.
Dependencies are inferred from the claim text.