反应 #2308003

反应方程式

7-hydroxy isoflavone

BF3

2,4-dihydroxyphenyl benzyl ketone

deoxybenzoin

→

compound 20

7-Hydroxy-2-ethoxycarbonylisoflavone

反应条件

后处理

1. 1
   其他were obtained
2. 2
   其他were prepared
3. 3
   其他All compounds synthesized
4. 4
   其他were purified by Sephadex-
5. 5
   其他Purity of all compounds prepared in this study

实验过程

Deoxybenzoins undergo α-keto formylation, intramolecular acetal formation, and a facile dehydration to give the pyrone ring C and hence, the isoflavones as shown in Scheme 1, Step 2 and below. Substituted deoxybenzoins were synthesized by reacting appropriate substituted phenyl acetic acids with properly substituted resorcinols in the presence of BF3. The starting material (7-hydroxy isoflavone, compound 1) for the synthesis of the 7-O-substituted isoflavones was prepared by cyclization of 2,4-dihydroxyphenyl benzyl ketone (Aldrich Chemical Co. Milwaukee, Wis.) as described by WO 91/15483, and shown in steps 2 and 3 of scheme 1, and further described in Gao et al. (2003) Bioorganic & Medicinal Chemistry, in press. 7-Hydroxy-2-ethoxycarbonylisoflavone (compound 20) was prepared by cyclization of the corresponding deoxybenzoin in the presence of an appropriate formyl equivalent as shown in Li, D. Y.; Gao, Z. J.; Ji, Q. E. Synthesis of isoflavones derivatives (I)-7-methoxy-3′-N, N-dialkylaminomethyl-4′-hydroxy isoflavones (Chinese J. Med. Chem. 1991, 1 (2), 38-42). The 2-carboxy derivatives (compounds 16, 21, and 22) were obtained by hydrolyzing their respective ethyl esters. The 4′-amino derivatives (compounds 32 and 33) were prepared by reducing their corresponding 4′-nitro derivatives (compounds 27 and 28) under the condition set forth in WO 91/15483, and Li, D. Y.; Gao, Z. J.; Ji, Q. E. Synthesis of isoflavones derivatives (I)-7-methoxy-3′-N, N-dialkylaminomethyl-4′-hydroxy isoflavones. Chinese J. Med. Chem. 1991, 1 (2), 38-42. Full explanations of the syntheses are set forth below. All compounds synthesized were purified by Sephadex-LH-20 and/or silica gel columns. Products were identified by 1HNMR, 13C-NMR, MS, and elemental analyses. Purity of all compounds prepared in this study was greater than 97.8% as judged by HPLC with UV detection at 254 mn. Molecular weights, melting points, molecular formulae, and elemental analysis data of these analogs are included in EXAMPLE IV, below.

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