Total Synthesis of (−)-Preussochromone A

Abstract

All non-aqueous reactions were carried out using flame-dried glassware under argon atmosphere. All solvents were distilled by rotary evaporation. Solvents for non-aqueous reactions were dried as follows prior to use: THF was distilled from Solvona®. CH2Cl2 was distilled from CaH2. MeOH and DMF were purchased from Acros Organics in extra dry quality and stored under an argon atmosphere over MS 4 Å. Toluene was distilled from Solvona®. DMSO was dried over CaSO4 overnight, distilled from CaH2 and stored over MS 4 Å. All commercially available reagents and reactants were used without purification unless otherwise noted.Reactions were monitored by thin layer chromatography (TLC) using Merck Silica Gel 60 F254-plates and visualized by fluorescence quenching under UV-light. In addition, TLC-plates were stained using a ceric sulfate/phosphomolybdic acid stain. Chromatographic purification of products was performed on Merck Silica Gel 60 (230-400 mesh) unless otherwise noted using a forced flow of eluents. Concentration under reduced pressure was performed by rotary evaporation at 40 °C and appropriate pressure and by exposing to fine vacuum at room temperature if necessary. NMR spectra were recorded on a Bruker AV 300 MHz, AV III 500 MHz, AV III HD 500 MHz spectrometer at room temperature. Chemical shifts are reported in ppm with the solvent resonance as internal standard. Data are reported as follows: s = singlet, d = doublet, t = triplet, q = quartet, quint = quintet, m = multiplet.Mass spectra were recorded by the mass service department of the Philipps-Universität Marburg. HR-ESI mass spectra were acquired with an LTQ-FT mass spectrometer (Thermo Fischer Scientific). The resolution was set to 100 000. IR spectra were recorded on a Bruker IFS 200 spectrometer. The absorption bands are given in wave numbers (cm -1 ), intensities are reported as follows: s = strong, m = medium, w = weak, br = broad band.Melting points were determined on a Mettler Toledo MP70 using one end closed capillary tubes.Diastereomeric ratios were accurately determined by integration of 1 H-NMR spectra.Optical rotations were determined at 20 °C for the Na-D wavelength (589 nm) with a Krüss P8000 T polarimeter. Absorption coefficient 2.366 mm -1 F(000) 560 Data collection: Diffractometer type STOE STADIVARI Wavelength 1.54186 Å Temperature 100(2) K Theta range for data collection 4.530 to 75.466°. Index ranges -10<=h<=12, -13<=k<=13, -16<=l<=9Data collection software X-Area Pilatus3_SV 1.31.127.0 (STOE, 2016) [2] Cell refinement software X-Area Recipe 1.33.0.0 (STOE, 2015) [3] Data reduction software X-Area Integrate 1.71.0.0 (STOE, 2016) [4] X-Area LANA 1.68.2.0 (STOE, 2016) [5] Solution and refinement: Reflections collected 24893Independent reflections 6509 [R(int) = 0.0201] Completeness to theta = 67.686° 99.3 % Observed reflections 6337[I > 2σ(I)]Reflections used for refinement 6509 Absorption correctionSemi-empirical from equivalents [5] Max. and min. transmission 0.4452 and 0.2044 Flack parameter (absolute struct.) 0.011(11) [6] Larges...

Synthetic Studies on Chromone Natural Products: The Preusso­chromones

“…Main problem probably was the β-elimination of the resulting anion VI , eliminating the side chain or opening the chromenone core which results in decomposition. 15…”

“…Oxidation of the thiomethyl group with mCPBA led to the desired sulfonylchromenone 55. 15 Thiol 56 was synthesized starting from known alcohol 60 (Scheme 15). 26 A Mitsunobu reaction with thiobenzoic acid gave, with inversion of configuration, thioester 61 in good yield.…”

“…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 2020, the Koert group disclosed the synthesis of (−)-preussochromone A (24), a fungal metabolite with a highly substituted tetrahydrothiopyrane core annulated to a chromenone [10]. The tetrahydrothiopyrane ring was closed by a Lewis-acid-promoted cycloisomerization of the α-ketoester 22, which can be described as a Friedel-Crafts-type reaction or an aldol reaction of an S,O-ketene acetal (Scheme 4).…”

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

“…Compound 1 shows moderate activity against human HeLa cells (IC 50 25.5 μM) and weak activity against A549 with an IC 50 value of 8.34 μM . Our ongoing interest in the synthesis of chromone-based natural products previously led to the synthesis of preussochromones A ( 1 ) and D ( 2 ). − Because of the synthetically challenging trans connection, we aimed for a total synthesis of 3 and 4 . Our synthetic plan for the synthesis of the trans -preussochromones is based on a ring-closing metathesis (RCM) to close the five-membered ring and subsequent bishydroxylation (Scheme ).…”