Total synthesis of (-)-mucocin and studies toward the asymmetric total synthesis of brianthein A

Total synthesis of (-)-mucocin and studies toward the asymmetric total synthesis of brianthein A Public Deposited

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A highly convergent asymmetric total synthesis of antitumor acetogenin natural product (-)-mucocin is described. This approach combined asymmetric glycolate aldol additions with ring-closing metatheses to construct cyclic ethers. In addition, a relay ring-closing metathesis strategy was successfully applied to the regioselective formation of an intermediate dihydrofuran. Finally, the two complex alkene fragments were coupled via a selective cross metathesis reaction. During efforts toward the asymmetric total synthesis of bioactive natural product brianthein A, a novel asymmetric aldol addition-thioimide transesterificationdianionic Claisen rearrangement strategy was developed. This strategy showcased the utility and versatility of the thiazolidinethione-mediated propionate aldol methodology previously developed in the Crimmins laboratories, and allowed rapid access to several complex intermediates containing all-carbon quaternary stereocenters in high yield and diastereoselectivity. Furthermore, synthesis of the highly functionalized trans-fused 6,10-bicyclic core of brianthein A was accomplished. By utilizing ring-closing metathesis as the key cyclization strategy, along with introducing an appropriate conformational constraint to the cyclization substrate, formation of the challenging ten-membered carbocycle was successful.

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