A Direct and Efficient Stereocontrolled Synthetic Route to the Pseudopterosins, Potent Marine Antiinflammatory Agents

Abstract

Described herein is a new synthetic route to pseudopterosin aglycone (3), a key intermediate for the synthesis of a group of antiinflammatory natural products including pseudopterosin A (1) and E (2). The pathway of synthesis starts with the abundant and inexpensive (S)-(-)-limonene and its long-known cyclic hydroboration product (4) and leads to the chiral hydroxy ketone 6. Conversion of 6 to 10 followed by a novel aromatic annulation produced 15 which underwent a highly diastereoselective cyclization to afford the protected pseudopterosin aglycone 16. The naturally occurring pseudopterosins such as 1 and 2 are readily available from this key intermediate.

C−C Bond Formation via C−H Bond Activation: Synthesis of the Core of Teleocidin B4

“…In this instance, the presence of the methoxy group meta to the amine facilitated the Friedel-Crafts reaction mediated by methanesulfonic acid, 11 providing racemic compound 5 in 83% yield (Scheme 1). Note that under anhydrous conditions, the Schiff base protection was retained, and the resultant product was ready for the second cycle of C-H activation/C-C bond formation without interruption.…”

Navigating the Chiral Pool in the Total Synthesis of Complex Terpene Natural Products

“…327 In this work, (−)-limonene was converted to ketone 259 via a three-step protocol previously developed by Corey. 317 Notably, the use of a cyclic hydroboration/oxidation strategy (thexylborane/H 2 O 2 ) was key in setting the stereocenter alpha to the future ketone selectively. 331 Chemoselective oxidation of the secondary alcohol (NaOCl) furnished ketone 258 .…”

Chemistry of Fluorinated Carbon Acids: Synthesis, Physicochemical Properties, and Catalysis

“…For example, 2,4-dialkylated triflylbenzenes 24e-h were obtained in good overall yields from the cyclohexenes through the thermal elimination of trifluoromethanesulfinic acid and subsequent aromatization using Corey's procedure. 43,44) Recently, triflylated aromatics including navitoclax (ABT-263) and ponazuril have attracted a great deal of attention in medicinal chemistry (Chart 20). Such highly substituted triflylarenes were traditionally synthesized through a combination of aromatic electrophilic substitution reactions.…”