Asymmetric Total Synthesis of Hasubanan Alkaloids: Periglaucines A–C, N,O‐Dimethyloxostephine and Oxostephabenine

Abstract

We report herein the asymmetric total synthesis of periglaucines A–C, N,O‐dimethyloxostephine and oxostephabenine. The key strategies used include: 1) a RhI‐catalyzed regio‐ and diastereoselective Hayashi‐Miyaura reaction to connect two necessary fragments; 2) an intramolecular photoenolization/Diels–Alder (PEDA) reaction to construct the highly functionalized tricyclic core skeleton bearing a quaternary center; 3) a bio‐inspired intramolecular Michael addition and transannular acetalization to generate the aza[4.4.3]propellane and the tetrahydrofuran ring.

Enantioselective Total Synthesis of (+)-Stephadiamine

“…Structurally, this class of natural products, sharing a common aza[4.4.3]­propellane core, differs mainly on the oxidation level of the polycyclic structure and the presence of an additional oxa-heterocycle. While the total synthesis campaign started in the late 1960s, asymmetric syntheses have been accomplished only recently. − …”

Streamlined Strategy for Scalable and Enantioselective Total Syntheses of the Eburnane Alkaloids

“…We envisioned completing the synthesis of (−)-dihydroeburnamenine 33 by direct catalytic reduction of the lactam moiety in (−)-eburnamonine 3 (Scheme b). Catalytic reduction of lactam 3 promoted by the Vaska’s complex [IrCl­(CO)­(PPh 3 ) 2 ] in the presence of 1,1,3,3-tetramethyldisiloxane as the terminal reductant delivered (−)-dihydroeburnamenine 33 in an 82% yield. Accordingly, we explored the possibility of using an inexpensive and more sustainable catalyst.…”

Total Synthesis of Metaphanine and Oxoepistephamiersine

“…In 2021, the Nagasawa group achieved the total synthesis of 2 via a biomimetic diastereoselective oxidative phenolic coupling and regioselective intramolecular aza ‐Michael reaction in 23 steps from commercially available 3‐hydroxy‐benzaldehyde [7b] . Very recently, Gao and co‐workers realized the total syntheses of periglaucines B−C ( 3 – 4 ) and their three congeners (not shown) by using an intramolecular photoenolization/Diels–Alder (PEDA) reaction and intermolecular regio‐/diastereoselective Miyaura–Hayashi reactions in 20 to 23 steps [7c] . Continuing our interest in the synthesis of complex polycyclic natural products, [8] we sought to develop a divergent strategy for the total synthesis of this subgroup hasubanan alkaloids.…”