Synthesis of the Hexahydropyrrolo-[3,2-c]-quinoline Core Structure and Strategies for Further Elaboration to Martinelline, Martinellic Acid, Incargranine B, and Seneciobipyrrolidine
Abstract
:1. Introduction
2. Total and Formal Synthesis of Martinellic Acid (2)
3. Tricyclic Core Scaffold Synthesis
4. Synthesis of Dipyrroloquinolines Towards Natural Products Seneciobipyrrolidine (3) and Incargranine B (4)
5. Elaborating Biological Properties
6. Concluding Remarks
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Compound | Optical Rotation [αD] | Concentration (mg/ 10 cm3) | Reference |
---|---|---|---|
1 (isolated) | +9.4 | 0.02 | [19] |
(−)-1 | −108.0 | 0.09 | [30] |
(+)-1 | +98.6 | 0.02 | [30] |
2 (isolated) | −8.5 | 0.01 | [19] |
(−)-2 | −122.7 | 0.37 | [29] |
(−)-2 | −118 | 0.3 | [32] |
(−)-2 | −164.3 | 0.14 | [30] |
(+)-2 | +165.5 | 0.11 | [30] |
(−)-2 | −164.8 | 0.33 | [31] |
3 (isolated) | −12 | 0.275 | [25] |
(±)-3 | −16.7 | 0.275 | [26] |
4 (isolated) | −72.9 | 0.10 | [27] |
Entry | Reaction Conditions | R1 | R2 | Enamide | Yield | Endo:Exo | Reference |
---|---|---|---|---|---|---|---|
1 | InCl3 (2 equiv.), MeCN, rt, 30 min | H | H | 73b | 41% | 1:1 | [58] |
2 | H | 2-NO2 | 73b | 50% | 2:1 | ||
3 | Zn(OTf)2 (10 mol%), DCM, rt | H | 2-OH | 73c | 42% | >20:1 | [59] |
4 | 76 (10 mol%), 5 Å MS, n-hexane −40 °C, 72 h | H | H | 73a | 94% | >20:1 | [60] |
5 | 77 (10 mol%), MeCN, rt, 0.5–1 h | H | H | 73a | 95% | 43:57 | [61] |
6 | 78 (10 mol%), MeCN, rt, 27 h | 4-OMe | H | 73d | 86% | 53:47 | [62] |
7 | Micellar-SO3H, H2O, 25 °C, 18 h | H | 4-O-DNA | 73d | >90% | NR | [63] |
Entry | Starting Material | Conditions | Yield a | Endo:Exo | Reference |
---|---|---|---|---|---|
1 | 240 | LiAlH4, ether, rt, 3.5 h | 27% | 38:36 | [100] |
2 | 242 | O3, n-hexane, 0 °C | 41% | NR | [101] |
3 | 242 | 1) DEAD, cyclohexane, reflux, 2 h, 80% 2) xylene, reflux, 15 h | 50% | 28:22 | [101] |
4 | 242 | γ-irradiation, 17 d | 9% | ~1:1 | [102] |
5 | 242 | di-t-butylperoxide, 140 °C, 44 h | NR | ~1:1 | [102] |
6 | 242 | Dibenzoyl peroxide, MeCN, 0 °C, 9 h | 28% | 1:0 | [102] |
7 | 242 | t-BuOOH, NaOAc•3H2O, cyclohexane 70 °C, 24 h | 72% | 1:0 | [103] |
8 | 242 | Cu(OAc)2, O2, Et3N | 26% | 11:15 | [104] |
9 | 240 | PhMe2SiLi, −78 to −20 °C | 47% | 31:16 | [105] |
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Haarr, M.B.; Sydnes, M.O. Synthesis of the Hexahydropyrrolo-[3,2-c]-quinoline Core Structure and Strategies for Further Elaboration to Martinelline, Martinellic Acid, Incargranine B, and Seneciobipyrrolidine. Molecules 2021, 26, 341. https://doi.org/10.3390/molecules26020341
Haarr MB, Sydnes MO. Synthesis of the Hexahydropyrrolo-[3,2-c]-quinoline Core Structure and Strategies for Further Elaboration to Martinelline, Martinellic Acid, Incargranine B, and Seneciobipyrrolidine. Molecules. 2021; 26(2):341. https://doi.org/10.3390/molecules26020341
Chicago/Turabian StyleHaarr, Marianne B., and Magne O. Sydnes. 2021. "Synthesis of the Hexahydropyrrolo-[3,2-c]-quinoline Core Structure and Strategies for Further Elaboration to Martinelline, Martinellic Acid, Incargranine B, and Seneciobipyrrolidine" Molecules 26, no. 2: 341. https://doi.org/10.3390/molecules26020341