Combined directed remote metalation-transition metal catalyzed cross coupling strategies: the total synthesis of the aglycones of the gilvocarcins V, M, and E and arnottin I.
A key directed remote metalation (DreM)-carbamoyl migration strategy was applied in an efficient synthesis of the naturally occurring 6H-naphtho[1,2-b]benzopyran-6-one defucogilvocarcin V (1a, Scheme 11). The required biarylcarbamate 33d was best prepared by a high yielding Suzuki coupling reaction of 31a with the differentially protected trioxygenated naphthalene coupling partner 32d which was synthesized using a selective acylation of a juglone derivative. In the late stages of the synthesis, the triflate 39 served as the common intermediate to install the required C-8 vinyl group of 1a (Stille coupling) as well as the required substituents for the preparation of defucogilvocarcins M (1b) and E (1c). A variety of protecting group strategies were investigated and provided insight into which groups are preferred for the DreM-carbamoyl migration process. The strategic lessons learned from this total synthesis were applied in the successful total synthesis of the structurally similar natural product arnottin I (2).
Department of Chemistry, University of Waterloo, Waterloo, ON, Canada N2L 3G1.
Clint A
CA
James
Victor
V
Snieckus
D001578:Benzopyrans / Q000138:chemical synthesis; D001688:Biological Products / Q000138:chemical synthesis; D002384:Catalysis; D003374:Coumarins / Q000138:chemical synthesis*; D006027:Glycosides; D028561:Transition Elements
D001578:Benzopyrans; D001688:Biological Products; D003374:Coumarins; D006027:Glycosides; D028561:Transition Elements; C414400:arnottin I; C031782:gilvocarcin M; C031781:gilvocarcin V; C047300:defucogilvocarcin V; C033792:gilvocarcin E