A New Method for the Synthesis of Kermesic Acid

doi:10.6023/cjoc202604007

Chinese Journal of Organic Chemistry ›› 2026, Vol. 46 ›› Issue (8): 3212-3218.DOI: 10.6023/cjoc202604007 Previous Articles Next Articles

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胭脂酮酸的合成新方法

高鑫^a, 张晓莹^a, 胡志飞^a^,^*(), 曹鸿志^a^,^b^,^c^,^*()

^a 中国海洋大学医药学院山东省糖科学与糖药物重点实验室青岛 266003
^b 中国海洋大学三亚海洋研究院三亚 572025
^c 青岛海洋科技中心海洋药物与生物制品实验室青岛 266237

收稿日期:2026-04-06 修回日期:2026-04-22 发布日期:2026-05-13
通讯作者: 胡志飞, 曹鸿志
基金资助:
国家重点研发计划(2025YFC3409500); 国家自然科学基金(92478131); 国家自然科学基金(22277111); 国家自然科学基金(22577125); 山东省重点研发计划（重大科技创新工程）(2024CXGC010615); 泰山学者特聘专家(TSTP20221114)

A New Method for the Synthesis of Kermesic Acid

Xin Gao^a, Xiaoying Zhang^a, Zhifei Hu^a^,^*(), Hongzhi Cao^a^,^b^,^c^,^*()

^a Key Laboratory of Marine Drugs of Ministry of Education, Shandong Key Laboratory of Glycoscience and Glycotherapeutics, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003
^b Sanya Oceanographic Institute, Ocean University of China, Sanya 572025
^c Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237

Received:2026-04-06 Revised:2026-04-22 Published:2026-05-13
Contact: Zhifei Hu, Hongzhi Cao
Supported by:
National Key Research and Development Program of China(2025YFC3409500); National Natural Science Foundation of China(92478131); National Natural Science Foundation of China(22277111); National Natural Science Foundation of China(22577125); Department of Science and Technology of Shandong Province(2024CXGC010615); Taishan Scholar Project(TSTP20221114)

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Abstract

Kermesic acid is an aromatic polyketide primarily isolated from cochineal insects, which has been widely employed as a natural red colorant. In the biosynthetic pathway, glycosylation of kermesic acid yields carminic acid, a compound of significant economic value with broad applications in dyes, cosmetics, food additives, and related industries. Accordingly, kermesic acid has attracted extensive attention as a key intermediate for the synthesis of carminic acid. Herein, a new chemical method for the synthesis of kermesic acid was reported. The key steps involve the in situ generation of arynes from bromoarenes followed by cyclization with phthalides, under the action of lithium diisopropylamide (LDA), enabling the rapid construction of the anthraquinone core and the convenient introduction of major functional groups. Subsequent manipulations, including oxidation state adjustment and demethylation, enabled the efficient total synthesis of kermesic acid in 9 steps with an overall yield of 12.5%, providing a crucial material foundation for functional studies of kermesic acid and the development of animal-free carminic acid synthesis.

Key words: kermesic acid, chemical synthesis, aryne-phthalide annulation, carminic acid

Cite this article

Xin Gao, Xiaoying Zhang, Zhifei Hu, Hongzhi Cao. A New Method for the Synthesis of Kermesic Acid[J]. Chinese Journal of Organic Chemistry, 2026, 46(8): 3212-3218.

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Fig. & Tab. 7

Figure 1. Structures of kermesic acid, isokermesic acid, and carminic acid

Scheme 1. Retrosynthetic analysis of Kermesic acid

Scheme 2. Model reaction of aryne-phthalide annulation

Scheme 3. Preparation of compound 4 and attempt of aryne-phthalide annulation reaction

Scheme 4. Synthesis and methylation transformation of compounds 15a and 15b

Position	¹H NMR δ_H		Δδ
Position	Reported 17	Synthetic 16a	Δδ
1-CH₃	2.63	2.65	0.02
2-CO₂CH₃; 3,5,6,8-OCH₃	3.93, 3.96, 3.97 (15H)	3.95, 3.96, 4.00, 4.01 (15H)	0.02~0.04
7-H	6.76	6.80	0.04
4-H	7.50	7.55	0.05

Table 1. Comparison of 1H NMR (400 MHz, CDCl3) data of compounds 16a and 17 reported in the literature

Scheme 5. Demethylation reaction of compound 15a

References 20

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胭脂酮酸的合成新方法

A New Method for the Synthesis of Kermesic Acid

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