Convergent Total Syntheses of (-)-Rubriflordilactone B and (-)-pseudo-Rubriflordilactone B

Abstract

A highly convergent strategy for the synthesis of the natural product (-)-rubriflordilactone B, and the proposed structure of (-)-pseudo-rubriflordilactone B, is described. Late stage coupling of diynes containing the respective natural product FG rings with a common AB ring aldehyde precedes rhodium-catalyzed [2+2+2] alkyne cyclotrimerization to form the natural product skeleton, with the syntheses completed in just one further operation. This work resolves the uncertainty surrounding the identity of pseudo-rubriflordilactone B and provides a robust platform for further synthetic and biological investigations.

Keywords: cyclotrimerization; natural products; schinortriterpenoids; structure elucidation; total synthesis.

Scheme 1

Rubriflordilactone B natural products, and our synthetic strategy.

Scheme 2

Synthesis of rubriflordilactone B diyne fragments. Ac=acetyl; BAIB=PhI(OAc)₂; CSA=(±)‐camphorsulfonic acid; DDQ=2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone; LDA=LiN(i‐Pr)₂; LiHMDS=LiN(SiMe₃)₂; NaHMDS=NaN(SiMe₃)₂; NMO=N‐methylmorpholine‐N‐oxide; PMB=4‐methoxybenzyl; TBAF=n‐Bu₄NF; TEMPO=(2,2,6,6‐tetramethylpiperidin‐1‐yl)oxyl; Tf=SO₂CF₃; TIPS=Si(i‐Pr)₃; TMS=SiMe₃.

Scheme 3

Synthesis of pseudo‐rubriflordilactone B diyne fragments. DIBALH=i‐Bu₂AlH; TBS=SiMe₂ t‐Bu; TPAP=tetrapropylammonium perruthenate.

Scheme 4

Late‐stage introduction of the butenolide G ring towards rubriflordilactone B.

Scheme 5

Synthesis of rubriflordilactone B and pseudo‐rubriflordilactone B. p‐Ts=p‐toluenesulfonyl.