尼亚那属二萜天然产物的全合成研究进展

doi:10.6023/cjoc202409037

摘要/Abstract

尼亚那属二萜是从中/南美洲大枫子科灌木中分离得到的一类天然产物, 是一类具有五环笼状结构、多个连续立体中心及高度氧化态的二萜天然产物. 生物学研究发现, 其成员ryanodine对心肌钙离子通道(PyR)具有专一的亲和调节作用, 是迄今发现的少数几个具有此功能的有机小分子化合物之一, 对心血管疾病的治疗具有潜在药用价值, 然而, 复杂的化学结构使得这类天然产物的合成充满了极大挑战. 综述了目前有机合成化学家对该类天然产物的全合成研究进展.

关键词: 尼亚那属二萜, 天然产物, 全合成

Ryania diterpene natural products were isolated from Ryania speciosa in the Central/South American, structurally which have a cage-type pentacyclic core, multiple continuous stereocenters, and a high oxidation state. Biological studies have found that its member ryanodine has a specific regulatory effect on myocardial calcium ion channels (PyR). It is one of the few organic small molecule compounds with this function discovered so far and has potential medicinal value for treating cardiovascular diseases. However, the complex chemical structure makes the synthesis of these natural products full of challenges. Herein the current research progress of organic chemists on the total synthesis of these natural products is reviewed.

Key words: ryania diterpenoid, natural product, total synthesis

引用此文

孟龙, 乔金宝, 赵玉明. 尼亚那属二萜天然产物的全合成研究进展[J]. 有机化学, 2025, 45(3): 804-813.

Long Meng, Jin-Bao Qiao, Yu-Ming Zhao. Progress on the Total Synthesis of Ryania Diterpenoids[J]. Chinese Journal of Organic Chemistry, 2025, 45(3): 804-813.

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图/表 12

图1. 代表性的尼亚那属二萜天然产物

Figure 1. Representative ryania diterpene natural product

图式1. ryanodol(3)的全合成

Scheme 1. Total synthesis of ryanodol (3)

图式2. 天然产物3-epi-ryanodol (4)的全合成

Scheme 2. Total synthesis of the natural product 3-epi-ryanodol (4)

图式3. ryanodol (3)的全合成

Scheme 3. Total synthesis of ryanodol (3)

图式4. ryanodine (1)的全合成

Scheme 4. Total synthesis of ryanodine (1)

图式5. ryanodine (1)和ryanodol (3)的不对称全合成

Scheme 5. Asymmetric total synthesis of ryanodine (1) and ryanodol (3)

图式6. 天然产物cinncassiols A, B (54, 6), cinnzeylanol (5)和3-epi-ryanodol (4)的全合成

Scheme 6. Total synthesis of the natural products cinncassiols A, B (54, 6), cinnzeylanol (5) and 3-epi-ryanodol (4)

图式7. (+)-ryanodol (3)的不对称全合成

Scheme 7. Asymmetric total synthesis of (+)-ryanodol (3)

图式8. 天然产物(+)-ryanodine (1)与(+)-20-deoxyspiganthine (8)的不对称全合成

Scheme 8. Asymmetric total synthesis of natural products (+)-ryanodine (1) and (+)-20-deoxyspiganthine (8)

图式9. Anhydroryanodol (20)的全合成

Scheme 9. Total synthesis of anhydroryanodol (20)

图式10. Garajonone (7)的全合成

Scheme 10. Total synthesis of garajonone (7)

项目	课题组	天然产物	关键步骤
1	Deslongchamps	(+)-Ryanodol (3), 3-epi-ryanodol (4)	分子间的Diels-Alder反应、氧化裂解/跨环的Aldol反应
2	Inoue	(+)-Ryanodine (1), (+)-ryanodol (3), 3-epi-ryanodol (4), cinnzeylanol (5), cinncassiols B (6), cinncassiols A (51)	自由基介导的C—C/C—O的偶联反应、RCM反应
3	Reisman	(+)-Ryanodine (1), (+)-ryanodol (3), (+)-20-deoxyspiganthine (8)	Pauson-Khand成环反应、二氧化硒介导的选择性氧化反应
4	Micalizio	Ryanodol (3)	钛介导的炔烃与1,3-二羰基分子内立体选择性的偶联反应
5	赵玉明	Garajonone (7)	钯催化Heck/插羰串联环化反应、氧化去芳构化、熔金属还原环化反应

表1. 尼亚那属二萜天然产物全合成的研究进展

Table 1. Progress in total synthesis of natural products of Ryania Diterpenoids

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