Synthesis, optical resolution, absolute configuration, and osteogenic activity of cis-pterocarpans

Abstract

A convenient synthesis of natural and synthetic pterocarpans was achieved in three steps. Optical resolution of the respective enantiomers was accomplished by analytical and semi-preparative HPLC on a chiral stationary phase. For medicarpin and its synthetic derivative 9-demethoxymedicarpin, the absolute configuration was confirmed by a combination of experimental LC-ECD coupling and quantum-chemical ECD calculations. (-)-Medicarpin and (-)-9-demethoxymedicarpin are both 6aR,11aR-configured, and consequently the corresponding enantiomers, (+)-medicarpin and (+)-9-demethoxymedicarpin, possess the 6aS,11aS-configuration. A comparative mechanism study for osteogenic (bone forming) activity of medicarpin (racemic versus enantiomerically pure material) revealed that (+)-(6aS,11aS)-medicarpin (6a) significantly increased the bone morphogenetic protein-2 (BMP2) expression and the level of the bone-specific transcription factor Runx-2 mRNA, while the effect was opposite for the other enantiomer, (-)-(6aR,11aR)-medicarpin (6a), and for the racemate, (±)-medicarpin, the combined effect of both the enantiomers on transcription levels was observed.

From α-Bromomethylbutenolide to Fused Tri(Tetra) Cyclic Dihydrofurandiones through Barbier Reaction–Heck Arylation Sequence

“…The structure of 4 was unambiguously assigned by NMR experiments. Our strategy represents an alternative to the construction of fused tricyclic lactone architectures combining fused cyclopentenone and dihydrofuranone or γ-lactone-fused benzopyrans [8,9,15,16,17]. After 16 h, we noticed full conversion of the starting material and lactone 4 was isolated in a fair 60% yield together with some unidentified degradation material (entry 2).…”

“…The interest of the scientific community for such lactones also stems from their use as intermediates in the synthesis of complex and polycyclic molecular architectures. As examples, the synthesis of the pterocarpan [8,9] and the podophyllotoxin skeletons illustrate α-methylidene butyrolactones as key intermediates for the construction of the final ring D and central ring B, respectively (Figure 1) [10,11,12,13]. …”

Assessment of Dihydro[1,3]oxazine‐Fused Isoflavone and 4‐Thionoisoflavone Hybrids as Antibacterials

“…For the synthesis of desired isoflavone and 4‐thionoisoflavone functionalized dihydro‐1,3‐oxazine hybrids ( 8 a – j and 9 a – d ), 6‐chloro‐7‐hydroxy‐3‐(2‐methoxy‐phenyl)‐chromen‐4‐one ( 4 ) and 6‐chloro‐7‐hydroxy‐3‐(2‐methoxy‐phenyl)‐chromene‐4‐thione ( 7 ) were synthesized as precursors by following the literature procedures [23–26] . Initially, Friedel‐Craft acylation of 4‐chlororesorcinol ( 1 ) was carried out by using 2‐methoxyphenylacetic acid ( 2 ) in presence of BF 3 ‐OEt 2 at 100–110 °C to afford corresponding deoxybenzoin ( 3 ) which on treatment with mesyl chloride in DMF, afforded a key starting material 6‐chloro‐7‐hydroxy‐3‐(2‐methoxy‐phenyl)‐chromen‐4‐one ( 4 ).…”

Medicarpin, a Natural Pterocarpan, Heals Cortical Bone Defect by Activation of Notch and Wnt Canonical Signaling Pathways

“…Med was synthesized in three steps with improved yield according to the modified procedure [ 22 ]. Briefly, med was prepared by a reaction of resorcinol and 2-(2,4-dimethoxyphenyl) acetic acid in the presence of lewis acid BF 3 -OEt 2 complex solution at 110°C with subsequent addition of mesyl chloride in DMF to furnish an intermediate 3-(2,4-dimethoxyphenyl)-7-hydroxy-4H-chromen-4-one followed by demethylation od 2’-methoxy group.…”