Utilizing the nitrogen-substituted donor-acceptor cyclopropane, enantiospecific total syntheses of (−)-hyacinthacine A₁⋅HCl and (+)-hyacinthacine A₁⋅HCl were achieved. The key reactions were highly stereo- and regioselective intramolecular cyclopropanation with rhodium(II) acetate and regioselective ring opening of nitrogen-substituted D−A cyclopropanes.

Abstract

A concise and efficient enantiospecific total synthesis of (−)-hyacinthacine A₁ and (+)-hyacinthacine A₁ was achieved from commercially available starting material L-pyroglutamic acid and D-glutamic acid, respectively. For the synthesis of this trihydroxylated pyrrolizidine ring, we employed the nitrogen-substituted donor-acceptor cyclopropane as a key intermediate. The synthetic approach relies on two crucial steps, highly stereo- and regioselective intramolecular cyclopropanation with Rh₂(OAc)₄ and regioselective ring opening of a nitrogen-substituted donor-acceptor cyclopropane.