Exploring the synthetic potential of epoxide ring opening reactions toward the synthesis of alkaloids and terpenoids: a review

Abstract

Epoxides are oxygen containing heterocycles which are significantly employed as crucial intermediates in various organic transformations. They are considered highly reactive three-membered heterocycles due to ring strain and they undergo epoxide ring opening reactions with diverse range of nucleophiles. Epoxide ring-opening reactions have gained prominence as flexible and effective means to obtain various functionalized molecules. These reactions have garnered substantial attention in organic synthesis, driven by the need to comprehend the synthesis of biologically and structurally important organic compounds. They have also found applications in the synthesis of complex natural products. In this review article, we have summarized the implementation of epoxide ring opening reactions in the synthesis of alkaloids and terpenoids based natural products reported within the last decade (2014-2023).

Fig. 1. General reaction of epoxide ring opening reaction.

Fig. 2. Structures of some biologically active natural products (Epothilone A 3, (±)-Merrilactone A 4, (±)-Epiasarinin 5, Methyl-l-callipeltose 6, (+)-8-Deoxyvernolepin 7).

Scheme 1. Synthesis of (−)-Citrinadin A 13a and (+)-Citrinadin B 16b.

Scheme 2. Synthesis of (−)-Chaetominine 26 and (±)-Cruciferane 27.

Scheme 3. Synthesis of Murrayakonine D 30.

Scheme 4. Synthesis of Weisaconitine D 35, Cochlearenine 39, Paniculamine 40, Veratroyldictyzine 42.

Scheme 5. Synthesis of optically active Cananodine 49a.

Scheme 6. Total synthesis of Alstolactine A 54.

Scheme 7. Synthesis of (−)-Melodinine K 60.

Scheme 8. Synthesis of Virdicatin 65.

Scheme 9. Synthesis of Siamine 69, Cassiarin A 71, and Rupreschstyril 75.

Scheme 10. Synthesis of Glyphaeaside C 84.

Scheme 11. Synthesis of tricyclic core 93 of Eurifoloid A 94.

Scheme 12. Synthesis of (±)-Brussonol 104 (±)-Komaroviquinone 106.

Scheme 13. Synthesis of (−)-Scabrolide A 116.

Scheme 14. Total syntheses of Marrubasch F 121, Marrubiin 121, Desertine 124b, Marrulibacetal 125a, Marrulibacetal A 125b, Marrulactone 129, Marrulanic acid 130 and Cyllenine C 132.

Scheme 15. First total synthesis of (±)-Rameswaralide 140.

Scheme 16. Synthesis of (+/−)-Anhydroryanodol 145.

Scheme 17. Synthesis of Isodehydrothyrsiferol 154.

Scheme 18. Total synthesis of Xiamycin 163 and Dixiamycin C 167.

Scheme 19. Synthesis of (−)-Siphonodictyal B 170 and (+)-Liphagal 171.

Scheme 20. Synthesis of Rhodonoids C 174, D 175 and 176.

Scheme 21. Regioselective synthesis of (+)-Heronapyrrole C 186.

Scheme 22. Syntheses of Guaiane-type sesquiterpenoids (Guaia-4(5)-en-11-ol 191, Aciphyllene 192, 1-epi-Melicodenones C 193, 1-epi-Melicodenones E 194, Guaia-5(6)-en-11-ol 195, 1-epi- Aciphyllene 198, 1-epi-Guaia-4(5)-en-11-ol 200).

Scheme 23. Hemisynthesis of Arglabin 203.

Scheme 24. Synthesis of (R)-α-Cuparenone 208, (R)-β-Cuparenone 210 and (S)-Cuparene 209.

Scheme 25. Synthesis of (±)-Isoclavukerin A 216.

Scheme 26. Total synthesis of (−)-Artatrovirenol A 226.