Yuehchukene

Yuehchukene is a dimeric indole alkaloid natural product that possesses anti-fertility and estrogenic activities. Yuehchukene is isolated from the roots of Murraya paniculata and other species of the plant genus Murraya. Its natural abundance is in the range of 10-52 ppm. Yuehchukene is a dimeric indole alkaloid natural product that possesses anti-fertility and estrogenic activities. Yuehchukene is isolated from the roots of Murraya paniculata and other species of the plant genus Murraya. Its natural abundance is in the range of 10-52 ppm. Yuehchukene consists of a tetracylic unit with a C6 indole substituent. Since its discovery no other natural product of similar structure has been found. Particularly, yuehchukene differs from other natural bis-indole alkaloids because it does not seem to be derived from tryptophan. The steric environments of the two nitrogen atoms are very different. One nitrogen is part of a rigid ring system and is shielded by the C6 indole. The other is part of the freely rotating indole making it readily assessable and therefore more reactive. Interest in this compound stems from its biological activity. Yuehchukene possesses a potent anti-fertility activity, with the (R)-(+)-enantiomer having been identified as the active form. The mode of action has been reported to be blockage of blastocyte implantation sites. Extensive structure-activity relationship investigations have been undertaken. Activity was found to be abolished by nitrogen substitution, 2, 5 and 5'-position substitution, hydroxylation of the benzene ring, hydroxylation of C9-C10 double bond and deletion of 7,7-dimethyl group. The activity was unaffected by saturation of the C9-C10 double bond. It was concluded that biological activity is dependent upon an optimal conformation defined by a narrowly fixed angle between the planes of the C6-indole and the tetracyclic unit. Yuehchukene also possesses estrogenic activity. This is interesting because the compound lacks oxygen functionalities and phenyl groups common to other natural or synthetic estrogen compounds. It is a mixed agonist/antagonist, binding competitively to rat uterine estrogen receptors, though with a very low binding affinity of ~1/300. Yuehchukene has not been developed as a pharmaceutical drug due to the effects of this estrogenic activity.