手性香料(–)-薄荷醇的不对称合成进展

doi:10.6023/cjoc202512024

摘要/Abstract

(–)-薄荷醇特有的风味使其在食品、医药及日化领域应用广泛. 持续增长的市场需求促使高效不对称合成方法的快速发展. 综述了(–)-薄荷醇的主流工业化合成路线与不对称催化前沿进展, 旨在梳理其合成策略的发展脉络与技术演进趋势. 目前工业上主要采用三条技术路线: Symrise路线以手性拆分获得产物; Takasago通过铑催化不对称异构化高选择性合成中间体; BASF则通过铑催化柠檬醛不对称氢化直接获得关键中间体香茅醛. 此外, 以胡椒烯酮为前体的还原路线及有机小分子催化的转移氢化策略也提供了合成多样性. 值得关注的是, List团队近期设计的手性强布朗斯特酸催化剂, 通过空间限域效应实现了柠檬醛的高选择性环化, 为开发步骤经济性和原子经济性的合成新工艺提供了借鉴.

关键词: (–)-薄荷醇, 不对称合成, 手性香料

The unique flavor of (–)-menthol makes it widely used in the fields of food, medicine, and daily chemicals. The continuously growing market demand has driven the rapid development of efficient asymmetric synthetic routes. This review summarizes the mainstream industrial synthesis routes and advances in asymmetric catalysis of (–)-menthol, aiming to outline the development and technological evolution of its synthetic strategies. Currently, three major technical pathways are predominantly employed in industrial production: the Symrise route obtains the target product via chiral resolution; the Takasago process achieves highly selective synthesis of key intermediates through rhodium-catalyzed asymmetric isome- rization. While the BASF route directly affords the crucial intermediate citronellal via rhodium-catalyzed asymmetric hydrogenation of citral. Furthermore, synthetic diversity is also provided by reductive strategies using piperitenone as a precursor and transfer hydrogenation approaches catalyzed by organocatalysts. Notably, the recent design of a chiral strong Brønsted acid catalyst by the List group, which enables highly selective cyclization of neral through a spatial confinement effect. This advancement offers a valuable paradigm for developing novel synthetic processes with enhanced step and atom economy.

Key words: (–)-menthol, asymmetric synthesis, chiral fragrances

引用此文

刘如灿, 唐杰, 朱立军, 马明, 胡旭东, 刘文博. 手性香料(–)-薄荷醇的不对称合成进展[J]. 有机化学, 2026, 46(6): 2267-2274.

Rucan Liu, Jie Tang, Lijun Zhu, Ming Ma, Xudong Hu, Wenbo Liu. Advances in the Asymmetric Synthesis of Chiral Fragrance (–)-Menthol[J]. Chinese Journal of Organic Chemistry, 2026, 46(6): 2267-2274.

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图/表 10

图1. 薄荷醇8种立体异构体的清凉感阈值(采用风味稀释法测定)

Figure 1. Cooling thresholds of the eight stereoisomers of menthol (by taste dilution analysis)

图式1. 植物体内(–)-薄荷醇的合成途径

Scheme 1. Biosynthetic pathway of (–)-menthol in plants

图式2. Symrise公司拆分策略的(–)-薄荷醇生产工艺

Scheme 2. Resolution process for (–)-menthol established by Symrise

图式3. Takasago公司不对称烯烃迁移策略的(–)-薄荷醇生产工艺

Scheme 3. Takasago process for (–)-menthol production via an asymmetric olefin isomerization strategy

图式4. BASF公司烯醛不对称氢化策略的(–)-薄荷醇生产工艺

Scheme 4. BASF process for (–)-menthol production via an asymmetric enal hydrogenation strategy

图式5. 万华化学不对称烯烃迁移策略的(–)-薄荷醇生产工艺

Scheme 5. Wanhua chemical process for (–)-menthol production via an asymmetric olefin isomerization strategy

图式6. Vasile Pârvulescu团队发展的多相催化体系用于(–)-薄荷醇合成

Scheme 6. Heterogeneous catalytic system developed by Vasile Pârvulescu’s team for the synthesis of (–)-menthol

图式7. Mashima或王林团队基于胡椒烯酮还原策略的(–)-薄荷醇合成路线

Scheme 7. A piperitenone-based reductive strategy for the synthesis of (–)-menthol by the Mashima or Wang Lin teams

图式8. List团队转移氢化策略实现(+)-香茅醛不对称合成

Scheme 8. Transfer hydrogenation strategy for the asymmetric synthesis of (+)-citronellal by the List team

图式9. List团队布朗斯特酸催化的柠檬醛不对称合成(–)-薄荷醇路线

Scheme 9. List group’s Brønsted acid-catalyzed asymmetric synthesis of (–)-menthol from citral

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