Recent Progress in the Synthesis of the Malagasy Alkaloids

doi:10.6023/cjoc202407032

Abstract

The Malagasy alkaloids have characteristic trans-fused C/D ring systems and multiple chiral centers, which pose great challenge for their synthesis research. These alkaloids also have potential synergistic anti-malarial activity, especially malagashanine as a natural sensitizer, which can enhance the sensitivity of drug-resistant plasmodium to chloroquine. The unique and challenging structure combined with preonunced pharmacological activity makes the synthesis of these natural products attractive, and their synthesis research also has important value for the development of new antimalarial drugs. The current research progress in the synthesis of the Malagasy alkaloidshis is summarized, including semi-synthesis, core skeleton construction, and total synthesis.

Key words: Malagasy alkaloids, total synthesis, skeleton construction, semi-synthesis, antimalarial activity

Cite this article

Weigang He, Yadong Liu, Yingkai Deng, Xianyu Sun. Recent Progress in the Synthesis of the Malagasy Alkaloids[J]. Chinese Journal of Organic Chemistry, 2025, 45(4): 1153-1165.

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Fig. & Tab. 16

Figure 1. Malagasy alkaloids and the related alkaloids

Figure 2. Chemosensitizers for antimalarial therapy

Scheme 1. Proposed biosynthetic pathways of the Malagasy alkaloids

Scheme 2. Trigalo group’s attempt at semi-synthesis of malagashanine

Scheme 3. Route for preparing the core skeleton of malagashanol by Canesi?s group

Scheme 4. Construction of tetracyclic skeleton of the Malagasy alkaloids using tandem cyclization strategy

Scheme 5. Construction of core skeleton of mattogrossine using tandem cyclization strategy

Scheme 6. Construction of core tetracyclic skeleton of indole alkaloid using the [2＋2＋2] cycloaddition strategy

Scheme 7. Construction of trans-fused skeleton through reduction reaction

Scheme 8. Construction of A/B/C tricyclic system through tandem Michael addition

Scheme 9. Total synthesis of magagashanine by Blakey’s group (I)

Scheme 10. Total synthesis of magagashanine by Blakey’s group (II)

Scheme 11. Blakey’s attempt to synthesize 11-demethoxymyrtoydine

Scheme 12. Tang and Wang’s total synthesis of myrtoidine analogue

Scheme 13. Waser’s formal synthesis of 11-demethoxy-16-epi-myrtoidine

Scheme 14. Total synthesis of the Malagasy alkaloids by Tang and Wang’s group

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Malagasy生物碱的合成研究进展