Preussochromone Puzzle: Structural Revision of Preussochromones E and F by Total Synthesis

Abstract

A stereoselective synthesis of the proposed and actual structures of the natural products preussochromones E and F is reported. The key step is a ring-closing metathesis to close the five-membered ring and install the trans configuration of the annulated five–six ring system. The analysis of the 3 J NMR couplings of the isolated natural product with the synthesized compound revealed its real structure with a cis annulation, which could also be synthesized using an intramolecular aldol reaction of a vic-tricarbonyl compound.

Synthetic Studies on Chromone Natural Products: The Preusso­chromones

“…In the end, using NaBH4 at low temperatures gave the desired natural product preussochromone E (53) in moderate yield, ultimately confirming its actual structure. 14 4 Total Synthesis of Preussochromone A…”

“…This finding laid the cornerstone for our approach towards preussochromones E (11) and F (12). 14 A Grubbs metathesis of trans-substituted diene 39 should establish the desired trans annulation, yielding cyclopentene 38 (Scheme 10). Diene 39 should be accessible by S N 1 enolate alkylation and methylenation.…”

“…The synthesis started with a challenging methylenation (Scheme 11 ). 14 Alcohol 40 was oxidized by IBX to its corresponding aldehyde which was directly employed in the olefination reaction using Nysted reagent and BF 3 ·OEt 2 . 22 Other methylenation attempts (e.g., Wittig) had problems with reproducibility and upscaling.…”

“…12 For these reasons we selected all four natural products as synthetic targets and review here our synthetic studies in the preussochromone field. [13][14][15] A retrosynthetic analysis led to a common general strategy for all four natural products using similar key steps (Scheme 1). The cyclopentanoide preussochromones D (10), E (11), and F (12) could be accessible by closure of the C7a-C7 bond via an intramolecular aldol reaction.…”

Vicinal ketoesters – key intermediates in the total synthesis of natural products

“…In a short and enantioselective total synthesis of preussochromone E (110) and F (109), Koert et al used the complex vic-tricarbonyl compound 108 to set two stereogenic centers and correct one via an intramolecular aldol addition (108 → 109; Scheme 18) [34]. The vic-tricarbonyl compound 108 was synthesized via DMDO oxidation from α-diazo-β-ketoester 107, which was easily accessible from 5-methoxy-4H-chromen-4one (106).…”