Synthesis of a C(1)–C(23) Fragment for Spirastrellolide E: Development of a Mechanistic Rationale for Spiroketalization

Abstract

Synthetic analysis of spirastrellolide E envisioned to entail a cross-metathesis union of the northern and southern hemispheres followed by a Sharpless epoxidation/methylation sequence to achieve the C(22,23) stereogenicity leads to the design of a C(1)–C(23) advanced southern hemisphere exploiting a gold-catalyzed directed spiroketalization as a key step. Stereochemical analysis of this strategic transformation provides insight on the impact of the directing group carbinol stereogenicity on the reaction efficiency and, in turn, permits the conversion of the minor isomer of the spiroketal precursor to the requisite congener for successful spiroketalization.

Total Synthesis of (−)-Secu’amamine A Exploiting Type II Anion Relay Chemistry

“…We subsequently demonstrated the potential of the two ARC tactics with the synthesis of a series of biologically important natural products, for example early studies on the construction of two frog alkaloids − utilizing the Type I tactic, and more recently in Diversity Oriented Synthesis with an effective, general protocol for the construction of all stereoisomers of a 2,4,6-trisubstituted piperidine library . Herein, we illustrate application of the ARC Type II multicomponent union tactic with a total synthesis of (−)-secu’amamine A ( 4 ).…”

Stereoselective Aldol Additions of Glycolic Acid and Its Derivatives

“…The yields are good as long as the oxazolidinone reacts to completion. 104,110,115,116,118,119,126 T. Engesser et al…”

Synthesis and Biological Evaluation of the Southern Hemisphere of Spirastrellolide A and Analogues

“…Protein phosphatases are recognized as potential targets in drug discovery for Parkinson’s disease, Alzheimer’s disease, and specifically tumor suppressors for blood cancers. − Due to these features, spirastrellolide is potentially a lead compound for anticancer therapeutics. This activity has inspired a significant amount of interest from the synthetic community resulting in elegant total syntheses − and synthetic strategies toward this natural product. − Despite its potency, a comprehensive biological evaluation of spirastrellolide A has not been undertaken, perhaps due to limited supplies from these studies or from natural sources. , Inspired by the eribulin work, we envisioned that SAR studies on simplified analogues of the marine macrolide spirastrellolide A might help identify the pharmacophore.…”