Kinesin motor protein inhibitor

Utilization of a similar [Sc(OTf)3-promoted)] approach by Overman on the ger-anylgeraniol-derived cyclization substrate 98 provided the desired tetracyclization product 99, in which the terminator of the cationic cyclization is an arene group. Compound 99 is then transformed into the kinesin motor protein inhibitor adocia-sulfate 1 (Scheme 8.27) [47]. 

Bogaistfitter, M. Limb g, A. Overman. L.E. Tmnasi, A.L. (1999) Enantioselective total synthesis of the kinesin motor protein inhibitor adociasulfate I. J. Am. Chem. Soc., 121,12206-7. 

Adociasulfates 1-6 (380-385) were isolated from a Haliclona (aka Adocia) sp. from Palau and were all inhibitors of kinesin motor proteins [331]. Adociasulfate 2 (381) had earlier been shown to inhibit the activity of the motor protein kinesin by interference with its binding to microtubules [332], An Adocia sp. from the Great Barrier Reef contained adociasulfates 1 (380), 7 (386) and 8 (387), which inhibit vacuolar H -ATPase [333]. Adociasulfates 5 (384) and 9 (388) were obtained from Adocia aculeata from the Great Barrier Reef [334], The structure of adociasulfate 1 (380) was confirmed by an enantioselective total synthesis [335]. Adociasulfate 10 (389) from Haliclona sp. from Palau also inhibits the kinesin motor proteins [336]. 

Monastrol Synthehc, idenhhed as cell-division inhibitor (24). Inhibits the kinesin-5 motor protein. 

Figure 1.9 Identification of monastrol (an inhibitor of the normal mitotic spindle formation) and its molecular target (a molecular motor protein, kinesin, Eg5) using chemical genomics.

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