Diastereocontrolled Formal Syntheses of (±)-Lepadiformines A, B, and C and the Divergent Synthesis of 2-epi-Lepadiformine C through Unexpected Double Consecutive Epimerizations

Abstract

We describe here the diastereocontrolled formal racemic syntheses of tricyclic marine alkaloids, lepadiformines A, B, and C as well as their C2 epimers, featuring divergent and stereoselective syntheses of the N-acetyl-8a-cyanodecahydroquinoline frameworks and the base-mediated intramolecular cyclization to establish the spiral quaternary center of the tricyclic framework from sterically well-defined α-aminonitrile 2. The approach allows us to accomplish the tricyclic core structure efficiently from readily available starting materials through simple operations. An unexpected pair of consecutive epimerizations at two contiguous stereocenters is observed on the basis of single-crystal X-ray analyses of the intermediates and derivatives. The findings have been successfully applied to the total synthesis of 2-epi-lepadiformine C. The epimerization mechanism has been elucidated through a series of deuterium-labelling-controlled experiments.

Conglomerate Crystallization in the Cambridge Structural Database (2020–2021)

“…Further examples of conglomerate crystallization were observed to have occurred within the synthesis of natural products in this updated distribution of the CSD, as shown in Figure (OWUREG, XOLNIY, and OCUGOM). Another example of a natural product structure, Sanctis B (SULHOZ), was noted to have crystallized as a conglomerate crystal.…”

Diastereoselective Synthesis oftrans‐anti‐Hydrophenanthrenes via Ti‐mediated Radical Cyclization and Total Synthesis of Kamebanin

“…Then, the resulting secondary alcohol was protected, and treated with 20 in the presence of KHMDS/TIPSOTf to produce enol ether 21 in 26 % yield, along with tetracyclic compound 22 in 63 % yield. We postulated that TIPSOTf activates the nitrile of 21 as a Lewis acid to generate the tetracyclic 22 in one step via a Thorpe‐Ziegler‐type reaction [19] . Therefore, the three‐step conversion from 21 to 22 using the intramolecular Mukaiyama aldol reaction [20] is unnecessary.…”

Expeditious Access to Spiro-Fused 2,5-Cyclohexadienones via Thio(seleno)cyanative ipso-Cyclization

“…To further widen the substrate choice, we tested the reactivity of N -(alkynoyl)-6-methoxytetrahydroquinolines with AgSCN in the presence of CAN to get pyrrolo-[2,1- j ]-quinolone, an inspiring structural motif found in tricyclic marine alkaloids . Gratifyingly, the domino thiocyanative ipso -cyclization of 3 progressed well, giving the thiocyanato-pyrrolo-[2,1- j ]-quinolone 4 in 80% yield (Scheme ).…”