黄烷酮的不对称合成研究进展

doi:10.6023/cjoc202109030

摘要/Abstract

黄烷酮及其衍生物是一种重要的生物活性的天然产物, 在很多复杂的天然产物中存在该骨架结构, 具有广泛的生物活性, 对于黄烷酮的研究越来越得到重视. 手性黄烷酮其本身在植物当中是种重要的化学物质, 具有潜在的药用价值, 但其含量较少, 很多化学家致力于通过合成的方法来解决问题, 推动了对映体富集的黄烷酮类的制备, 但其制备过程存在一定的局限性, 对于一些复杂结构的黄烷酮类化合物仍很难实现, 这将是未来需要攻克的难题. 本文综述了近年来黄烷酮的不对称合成方法. 合成方法包括对羰基的还原、手性拆分、碳-碳键的形成、碳-杂键的形成及其他类型的合成方法.

关键词: 黄烷酮, 不对称合成, 综述

Flavanones and their derivatives are important bioactivenatural products. The skeleton structure exists in many complex natural products and has a wide range of biological activities. The research on flavanones is getting more and more attention. Chiral flavanone itself is an important chemical substance in plants and has potential medicinal value, but its content is small. Many chemists are committed to solve the problem through synthetic methods, which promotes the preparation of enantiomerically enriched flavanones. The preparation process has certain limitations, but for some complex structures of flavanone compounds it is still difficult to achieve, This is going to be a problem to overcome in the future. The asymmetric synthesis methods of flavanones are reviewed in recent years. The synthesis methods include carbonyl reduction and chiral resolution of raceme, formation of carbon-carbon bonds, formation of carbon-heterobonds and other types of synthesis methods.

Key words: flavanones, asymmetric synthesis, review

引用此文

王立花, 公绪顺, 雷婷, 江世智. 黄烷酮的不对称合成研究进展[J]. 有机化学, 2022, 42(3): 758-769.

Lihua Wang, Xushun Gong, Ting Lei, Shizhi Jiang. Research Progress on Asymmetric Synthesis of Flavanones[J]. Chinese Journal of Organic Chemistry, 2022, 42(3): 758-769.

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图/表 30

图式1. 钌催化的黄酮类化合物1的不对称氢化反应

Scheme 1. Ruthenium-catalyzed asymmetric hydrogenation of flavonoids 1

图式2. 利用L-(+)-2,3-丁二硫醇对外消旋黄烷酮4进行拆分

Scheme 2. Resolution of racemic flavanone 4 with L-(+)-2,3-butanedithiol

图式3. 黄烷酮类化合物4通过转化成顺式胺类化合物6a和6b进行拆分

Scheme 3. Flavanone compound 4 resolved by converting into cis-amine compounds 6a and 6b

图式4. 铑催化的外消旋黄烷酮衍生物的非酶动力学拆分

Scheme 4. Rhodium-catalyzed nonenzymatic kinetic resolution of racemic flavanone derivatives

图式5. 外消旋黄烷醇酯8的酶促动力学拆分

Scheme 5. Enzymatic kinetic resolution of racemic flavanol ester 8

图式6. 外消旋黄烷酮肟乙酸酯9的酶促动力学拆分

Scheme 6. Enzymatic kinetic resolution of racemic flavanone oxime acetate 9

图式7. Mitsunobu反应与酶促拆分结合生成对映体富集的黄烷酮对映体

Scheme 7. Mitsunobu reaction combined with enzymatic resolution to generate enantiomerically enriched flavanone enantiomers

图式8. 利用手性亚砜结构通过共轭加成合成手性黄烷酮类化合物

Scheme 8. Synthesis of chiral flavanones by conjugate addition using chiral sulfoxide structure

图式9. 在C2对称手性双亚砜配体存在下铑催化色酮与四芳基硼酸钠的不对称1,4-加成反应

Scheme 9. Rhodium catalyzed asymmetric 1,4-addition reactions of chromone with sodium tetraarylborate in the presence of C2 chiral disulfone ligand

图式10. 铑催化芳基硼酸对色烯酮18的1,4-对映选择性加成反应

Scheme 10. Rh-catalyzed enantioselective 1,4-addition of arylboronic acids to chromenones 18

图式11. 铑催化芳基硼酸与色酮的不对称共轭加成

Scheme 11. Rhodium-catalyzed asymmetric conjugate addition of arylboronic acid to chromone

图式12. 铑催化色酮与苯基硼酸的不对称1,4-加成反应

Scheme 12. Rhodium-catalyzed asymmetric 1,4-addition reaction of chromone and phenylboronic acid

图式13. 铑催化芳基硼酸与色酮的不对称1,4-加成反应

Scheme 13. Rhodium-catalyzed asymmetric 1,4-addition reaction of arylboronic acid and chromone

图式14. Pd/PyOX催化芳基硼酸与色酮的不对称共轭加成反应

Scheme 14. Pd/PyOX catalyzed the asymmetric conjugate addition reaction of aryl boronic acid and chromone

图式15. 利用配体1,10-菲咯啉催化苯基硼酸与色酮的不对称1,4-加成

Scheme 15. Asymmetric 1,4-addition of phenylboronic acid and chromone catalyzed by ligand 1,10-phenanthroline

图式16. 手性硫脲催化黄烷酮的对映选择性合成

Scheme 16. Enantioselective synthesis of flavanone catalyzed by chiral thiourea

图式17. Ni (29)催化的α,β-不饱和酮的不对称分子内Oxa- Michael加成反应

Scheme 17. Ni (29)-catalyzed asymmetric intramolecular Oxa- Michael addition reaction of α,β-unsaturated ketones

图式18. 手性N-三氟磷酰胺催化的α,β-不饱和酮的不对称分子内Oxa-Michael加成反应

Scheme 18. Asymmetric intramolecular oxa-Michael addition reaction of α,β-unsaturated ketones catalyzed by chiral N-trifluorophosphoramide

图式19. 双功能金鸡纳生物碱催化的Oxa-Michael加成/脱羧反应

Scheme 19. Oxa-Michael addition/decarboxylation reaction catalyzed by bifunctional cinchona alkaloid

图式20. 金鸡纳生物碱催化2,6-二羟基查尔酮32的不对称环化反应

Scheme 20. Cinchona alkaloid catalyzed the asymmetric cycli- zation of 2,6-dihydroxychalcone 32

图式21. 2-羟基查尔酮可逆环化为黄烷酮的不对称离子对催化

Scheme 21. Asymmetric ion pair catalysis for the reversible cyclization of 2-hydroxychalcone to flavanone

图式22. 2-羟基查尔酮的对映选择性仿生环化合成黄烷酮

Scheme 22. Synthesis of flavanones by enantioselective bionic cyclization of 2-hydroxychalcone

图式23. 仿生查尔酮环化反应

Scheme 23. Bionic chalcone cyclization reaction

图式24. S-三嗪催化2-羟基查尔酮的不对称环化反应

Scheme 24. S-Ttriazine-catalyzed asymmetric cyclization of 2-hydroxychalcone

图式25. Mitsunobu法合成(S)-(–)-Pinostrobin

Scheme 25. Synthesis of (S)-(–)-pinostrobin by Mitsunobu method

图式26. Mitsunobu法合成(S)-(-)-Pinostrobin

Scheme 26. Synthesis of (S)-(-)-pinostrobin by Mitsunobu method

图式27. 双功能金鸡纳生物碱催化串联分子内Oxa-Michael加成/亲电氟化反应

Scheme 27. Bifunctional cinchona alkaloids catalyze tandem intramolecular oxa-Michael addition/electrophilic fluorination reaction

图式28. 分子内Oxa-Michael加成/亲电卤代串联反应

Scheme 28. Intramolecular oxa-Michael addition/electrophilic halogenation tandem reaction

图式29. MBH碳酸酯与苄胺的对映选择性串联反应

Scheme 29. Enantioselective tandem reaction of MBH carbonate and benzylamine

图式30. 分子内的安息香反应立体选择性的合成黄烷酮

Scheme 30. Stereoselective synthesis of flavanones by intramolecular benzoin reaction

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