Ryanodol (1) exists in nature in the form of the 1H-pyrrole-2-carboxylate ester derivative known as ryanodine, which is a potent modulator of the calcium release channel. The pentacyclic ABCDE-ring system of 1 is fabricated with eight oxy groups, three methyl groups, and one isopropyl group. All the eight tetrasubstituted stereocenters are concentrated within the 10-carbon ABDE framework. The total synthesis of this exceptionally complex molecule was achieved in 22 steps from the simple C2-symmetric tricycle 8. The synthetic route is based on installation of the seven stereogenic centers and formation of the four C-C bonds within the highly congested multicyclic format. The novel and flexible strategy developed here will enable the generation of chemical derivatives with different functional properties toward calcium release channels.
The fused 6/7/5/6/6-membered (ABCDE) ring system of talatisamine was synthesized in 22 steps. After preparation of the AE-ring structure from 2-(ethoxycarbonyl)cyclohexanone, elaboration of the carboskeleton was realized by sequential additions of allyl magnesium bromide and the lithiated C-ring. The C11-bridgehead radical derived from the ACE-ring underwent the 7-endo cyclization with the enone moiety to form the B-ring in C10-stereoselective and C11-stereospecific manners. The 6-endo cyclization of the remaining D-ring was in turn attained by using the silyl enol ether as the nucleophile and the PhSeCl-activated olefin as the electrophile. These radical and cationic cyclizations were demonstrated to be highly chemoselective, and they significantly contributed to streamlining the route to the intricately fused pentacycle of talatisamine.
The unique hexacyclic ring system of puberuline C was efficiently synthesized utilizing a radical-based cyclization/translocation/cyclization process and Mukaiyama aldol reaction.
SummaryThe stereoselective Diels–Alder reaction between an optically active 1,4-dimethylcycloheptadiene and acrolein was effectively promoted by TBSOTf to produce a bicyclo[3.2.2]nonene derivative bearing two quaternary carbons. Seven additional transformations from the obtained bicycle delivered the C
2-symmetric bicyclo[3.3.2]decene derivative, a key intermediate in our synthetic study of ryanodine.
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