Stereocontrolled total synthesis of (+)-trans-dihydronarciclasine.
A highly stereoselective and efficient total synthesis of trans-dihydronarciclasine from a readily available chiral starting material was developed. The synthesis defines two of the five stereogenic centers of the natural product by an amino acid ester-enolate Claisen rearrangement. The other three stereogenic centers are created in a highly stereocontrolled fashion via a six-ring vinylogous ester intermediate, which is generated from the γ,δ-unsaturated ester functional group of the Claisen rearrangement product in an efficient three-step sequence. This concise total synthesis exemplifies the use of a highly regioselective Friedel-Crafts-type cyclization to form the B ring via an isocyanate intermediate derived from an N-Boc group, which is superior to the conventional method using an imino triflate intermediate. This same N-Boc group is employed to give high selectivity in the Claisen rearrangement earlier in the sequence.
College of Pharmacy, Seoul National University, San 56-1, Shilim, Kwanak, Seoul 151-742, Korea.
Soonho
S
Hwang
Deukjoon
D
Kim
Sanghee
S
Kim
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry*; D003500:Cyclization; D004952:Esters; D015394:Molecular Structure; D013237:Stereoisomerism
D000470:Alkaloids; D004952:Esters; C064338:dihydronarciclasine