Asymmetric Biomimetic Oxidations of Phenols: Enantioselective Synthesis of (+)- and (-)-Dehydrodiconiferyl Alcohol

Abstract

Stereoselective bimolecular radical coupling reactions of phenylpropenoid phenols are described. Oppolzer's camphor sultam 1 and Evans's 2-oxazolidinone 2a-d derivatives of ferulic acid were prepared and oxidized to give dimeric benzofuran neolignan structures 11 in 40-50% overall yields. The chiral phenols were oxidized either enzymatically with hydrogen peroxide and horseradish peroxidase (HRP) or by silver oxide. The observed enantioselectivity after reductive cleavage of chiral auxiliaries gave the neolignan dehydrodiconiferyl alcohol 12 in 18-84% e.e.

Novel Conjugates of Aspirin with Phenolic Acid as Anti‐inflammatory Agents Having Significantly Reduced Gastrointestinal Toxicity

“…The key intermediate 3a [15] was generated by treating the acid chloride of aspirin directly with excessive 2a, while compound 3b was synthesized by coupling aspirin with 2c in the presence of DCC-DMAP and followed by debenzyla-tion. With the two aspirin derivatives 3a, b in hand, six derivatives 4a-f [16][17][18][19][20][21] of the three natural antioxidants 1a-c bearing different phenolic hydroxyl protecting groups were coupled with 3a, b to provide 5a-i either through their acid chlorides or promoted by DCC-DMAP directly. Removal of the acetyl group on 5a-c using 3 M HCl in acetone led to compounds 6a-c (Scheme 1).…”

Podophyllotoxin and Antitumor Synthetic Aryltetralines. Toward a Biomimetic Preparation

“…The enzymatic oxidative coupling of ferulic acid derivatives was observed by us to result in the diastereoselective synthesis of benzo [b]phenylcoumarans (Bolzacchini et al, 1998). Stereocontrol in this reaction to enantioselectively give benzo [b]phenylcoumarans has been recently shown by us to be possible (Rummalko et al, 1999) using a chiral inducer and the horseradish peroxidase (HRP)-catalyzed oxidative coupling in presence of hydrogen peroxide as the oxidant. The chiral inducers were aminoacid ethyl esters, camphorsultam and aryloxazolidinones (Bruschi et al, 2006).…”

The Stereoselective Synthesis of Neolignans

“…91 On the other hand, an enzyme fraction from the leaves of Piper regnellii converted 4-hydroxyphenylpropene (27) to conocarpan (29) (see Scheme 4) in 85% ee, 55 whereas oxidation of coniferyl alcohol (2) using the cell-free extracts of Eucommia ulmoides provided racemic dehydrodiconiferyl alcohol (16) and an optically active 8-O-4¢-dehydrodimer. 92 An alternative approach, in which chiral auxiliaries, covalently bonded to phenylpropenes, were prepared and diastereoselectively dimerized, was developed by Orlandi et al Following their strategy, ferulic acid (1) was reacted with phenyl-and benzyloxazolidinones, 93 with camphor sultam 6,93 and with alanine ethylester 6,94 affording the chiral amides 78-81. These amides were subjected to the oxidative dimerization by either horseradish peroxidase/ H 2 O 2 or Ag 2 O.…”