The structures of metabolites produced in microgram quantities by enzymatic reductions with baker's yeast were analyzed using the crystalline sponge method. The crystalline sponge method coupled with HPLC purification would be a useful method for metabolic analysis and drug discovery.
An enantioselective route to the tetracyclic skeleton of sarain A has been developed. Asymmetric reduction of an ynone introduced a chiral center which was transferred to the contiguous tertiary stereogenic centers through an Ireland-Claisen rearrangement. The 2-azabicyclo[3.3.1]nonane framework was constructed by an unprecedented intramolecular cycloaddition of an eight-membered cyclic nitrone. Using the steric bias of the bicyclic system, the quaternary carbon atom was constructed by a stereoselective aldol reaction. Further ring formations were performed by ring-closing metathesis for the 13-membered ring and an iodoamidation reaction for the pyrrolidine ring. The present synthesis has successfully provided an alternative route to the late-stage intermediate of Overman's synthesis.
An enantioselective route to the tetracyclic skeleton of sarain Ah as been developed. Asymmetric reduction of an ynone introduced ac hiral center which was transferred to the contiguous tertiary stereogenic centers through an Ireland-Claisen rearrangement. The 2-azabicyclo[3.3.1]nonane framework was constructed by an unprecedented intramolecular cycloaddition of an eight-membered cyclic nitrone.U sing the steric bias of the bicyclic system, the quaternary carbon atom was constructed by astereoselective aldol reaction. Further ring formations were performed by ring-closing metathesis for the 13-membered ring and an iodoamidation reaction for the pyrrolidine ring. The present synthesis has successfully provided an alternative route to the late-stage intermediate of Overmans synthesis.
Formal Synthesis of Sarain A: Intramolecular Cycloaddition of an Eight-Membered Cyclic Nitrone to Construct the 2-Azabicyclo[3.3.1]nonane Framework. -A synthetic route to the tetracyclic skeleton of sarain A is developed, featuring an intramolecular cycloaddition of an eight-membered cyclic nitrone to construct the 2-azabicyclo[3.3.1]nonane framework and an iodoamidation reaction to form the pyrrolidine ring. This approach provides an alternative route to the intermediate in Overman's synthesis of sarain A. -(HIGO, T.; UKEGAWA, T.; YOKOSHIMA*, S.; FUKUYAMA, T.; Angew. Chem., Int. Ed. 54 (2015) 25, 7367-7370, http://dx.
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