RESUMO
The successful synthesis of the highly complex model compound (2) of the CEFGH ring system of schindilactoneâ A (1) is described. Several synthetic methodologies were developed and applied to achieve this goal, including ring-closing metathesis (RCM) and Co-thiourea-catalyzed Pauson-Khand reactions. Furthermore, two independent approaches were developed for the construction of the GH ring of model compound 2, the key steps of which included Pd-thiourea-catalyzed carbonylative annulation, methylation, and sequential RCM/oxa-Michael-addition reactions. The chemistry developed herein has provided a greater understanding of the synthesis of schindilactoneâ A (1) and its analogous compounds of the same family.
Assuntos
Triterpenos/síntese química , Catálise , Cristalografia por Raios X , Ciclização , Lactonas/química , Metilação , Conformação Molecular , Paládio/química , Estereoisomerismo , Tioureia/química , Triterpenos/químicaRESUMO
The final phase for the total synthesis of (±)-schindilactoneâ A (1) is described herein. Two independent synthetic approaches were developed that featured Pd-thiourea-catalyzed cascade carbonylative annulation reactions to construct intermediate 3 and a RCM reaction to make intermediate 4. Other important steps that enabled the completion of the synthesis included: 1)â A Ag-mediated ring-expansion reaction to form vinyl bromide 17 from dibromocyclopropane 30; 2)â a Pd-catalyzed coupling reaction of vinyl bromide 17 with a copper enolate to synthesize ketoester 16; 3)â a RCM reaction to generate oxabicyclononenol 10 from diene 11; 4)â a cyclopentenone fragment in substrate 8 was constructed through a Co-thiourea-catalyzed Pauson-Khand reaction (PKR); 5)â a Dieckmann-type condensation to successfully form the Aâ ring of schindilactoneâ A (1). The chemistry developed for the total synthesis of schindilactoneâ A (1) will shed light on the synthesis of other family members of schindilactoneâ A.