11024-56-9Relevant academic research and scientific papers
Total Synthesis of Paspaline A and Emindole PB Enabled by Computational Augmentation of a Transform-Guided Retrosynthetic Strategy
Kim, Daria E.,Zweig, Joshua E.,Newhouse, Timothy R.
, p. 1479 - 1483 (2019)
We report the total syntheses of two indole diterpenoid natural products, paspaline A and emindole PB. Paspaline A is synthesized in a 9-step sequence from commercially available materials. The first total synthesis of emindole PB is accomplished in 13 steps and confirms a previously ambiguous structural assignment. Density functional theory calculations are utilized to interrogate the key carbocationic rearrangement in a predictive capacity to aid in the selection of the most favorable precursor substrate. This work highlights how retrosynthetic design can be augmented with quantum chemical calculations to reveal energetically feasible synthetic disconnections, minimizing time-consuming and expensive empirical evaluation.
Asymmetric Total Synthesis of the Indole Diterpene Alkaloid Paspaline
Sharpe, Robert J.,Johnson, Jeffrey S.
, p. 9740 - 9766 (2015/10/12)
An enantioselective synthesis of the indole diterpenoid natural product paspaline is disclosed. Critical to this approach was the implementation of stereoselective desymmetrization reactions to assemble key stereocenters of the molecule. The design and execution of these tactics are described in detail, and a thorough analysis of observed outcomes is presented, ultimately providing the title compound in high stereopurity. This synthesis provides a novel template for preparing key stereocenters in this family of molecules, and the reactions developed en route to paspaline present a series of new synthetic disconnections in preparing steroidal natural products.
A global and local desymmetrization approach to the synthesis of steroidal alkaloids: Stereocontrolled total synthesis of paspaline
Sharpe, Robert J.,Johnson, Jeffrey S.
, p. 4968 - 4971 (2015/05/05)
A stereocontrolled total synthesis of the indole diterpenoid natural product paspaline is described. Key steps include a highly diastereoselective enzymatic desymmetrization, substrate-directed epoxidation, Ireland-Claisen rearrangement, and diastereotopi
Indole Diterpene Synthetic Studies. 2. First-Generation Total Synthesis of (-)-Paspaline
Mewshaw, Richard E.,Taylor, Michael D.,Smith, Amos B.
, p. 3449 - 3462 (2007/10/02)
We record here a full account of the first total synthesis of (-)-paspaline (1), the simplest member of a rapidly growing class of architecturally complex diterpene indole alkaloids, many of which possess potent tremorgenic activity.In terms of sequential annulation, the strategy involves the following operations: DE -> CDE -> CDEF -> ABCDEF.Proceeding in 23 steps from Wieland-Miescher ketone, the synthesis afforded (-)-paspaline (1) in high enantiomeric purity.
