doi: 10.1002/anie.201601834. Epub 2016 Apr 27.
Synthesis of (-)-Cannabimovone and Structural Reassignment of Anhydrocannabimovone through Gold(I)-Catalyzed Cycloisomerization
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- PMID:27119910
- PMCID: PMC5053274
- DOI: 10.1002/anie.201601834
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Synthesis of (-)-Cannabimovone and Structural Reassignment of Anhydrocannabimovone through Gold(I)-Catalyzed Cycloisomerization
Javier Carreras et al. Angew Chem Int Ed Engl..
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Abstract
The first total synthesis of cannabimovone from Cannabis sativa and anhydrocannabimovone was achieved by means of a highly stereoselective gold(I)-catalyzed cycloisomerization. The results led to reassignment of the structure of anhydrocannabimovone.
Keywords: cannabinoids; cycloisomerization; gold; oxy-Michael reaction; total synthesis.
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Figures
Cannabinoids THC (1), CBD (2), and cannabimovone (3).
Synthesis of anhydrocannabimovone (6) from cannabidiol (CBD,2).9
Retrosynthetic analysis for3 and6.
a) LDA, HMPA, prenyl bromide, THF, −70 °C to −10 °C, 3 h, 81 %; b) TBSCl, DBU, CH2Cl2, 25 °C, 14 h, 89 %; c) DIBAL‐H, Toluene, −78 °C to −50 °C, 4 h, 84 %; d) Oxalyl chloride, DMSO, Et3N, CH2Cl2, −60 °C to 25 °C, 1 h; e) Ohira–Bestmann reagent, K2CO3 MeOH, 25 °C, 5 h, 51 % (2 steps); f) Pd(PPh3)2Cl2 (5 mol %), CuI (10 mol %), Et3N/iPr2EtN (1:1), 25 °C, 16 h, 83 %; g) [(JohnPhos)Au(MeCN)]SbF6 (5 mol %), CH2Cl2 1 m , 25 °C, 30 min, 49 %; h) [(JohnPhos)Au(MeCN)]SbF6 (5 mol %), MeOH 1 m , 25 °C, 30 min, 93 %. i) [(JohnPhos)Au(MeCN)]SbF6 (5 mol %), DMSO 0.5 m , 25 °C, 3 h, 88 %. LDA=lithium diisopropylamide, HMPA=hexamethylphosphoramide, THF=tetrahydrofuran, TBSCl=tert‐butylsilyl chloride, DBU=1,8‐diazabicyclo[5.4.0]undec‐7‐ene, DIBAL‐H=diisobutylalane, DMSO=dimethyl sulfoxide, JohnPhos=(2‐biphenyl)‐di‐tert‐butylphosphine.
a) mCPBA, NaHCO3, CH2Cl2, 0 °C to 25 °C, 3 h, 57 %; b) BF3⋅OEt2, THF, 25 °C, 30 min, 93 %; c) HCl dil./THF, 25 °C, 1 h, 88 %; d) TBAF, THF, 25 °C, 14 h, 83 %; e) mCPBA, NaHCO3, CH2Cl2, 0 °C to 25 °C, 4 h, 58 %; f) BF3⋅OEt2, THF, 25 °C, 1 h, 48 %; g) NaBH(OAc)3, CH2Cl2, 25 °C, 48 h, 48 % (77 % brsm); h) AllocCl, TMEDA, CH2Cl2, −40 °C, 1.5 h, 41 % (72 % brsm); i) DMP, NaHCO3, CH2Cl2, 25 °C, 1.5 h, 87 %; j) MgBr2, BnSH, Et2O, 25 °C, 30 h, 62 %; k) Pd(PPh3)4 (5 mol %), dimedone, THF, 25 °C, 1 h, 85 %.mCPBA=m‐chloroperbenzoic acid, TBAF=tetrabutylammonium fluoride, Alloc=allyloxycarbonyl, TMEDA=tetramethylethylenediamine, DMP=Dess–Martin periodinane.
a) m‐ClC6H4CO2H, CH2Cl2, 25 °C, 1 h, 77 %; b) ZnI2, (NaBH4), (CH2Cl)2, 25 °C, 14 h, 63 %. X‐Ray structure for21.
X‐Ray structures for6 and23.
a) Ac2O, Et3N, DMAP, CH2Cl2, −30 °C, 1 h, 50 % (56 % brsm); b) DMP, NaHCO3, CH2Cl2, 25 °C, 1 h, 73 %; c) MgBr2, BnSH, Et2O, 25 °C, 24 h, 82 %; d) K2CO3, MeOH, 25 °C, 15 min, 60 % (6) and 19 % (6′′).
Energy profile (cis andtrans) for the oxy‐Michael cyclization. DFT calculations (M06‐2x/6‐31G(d,p) (MeOH), ΔG (kcal mol−1).
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References
- None
- Thakur G. A., R. I. Duclos Jr , Makriyannis A., Life Sci. 2005, 78, 454–466; - PubMed
- Marijuana and the Cannabinoids (Ed. M. A. ElSohly), Humana, Totowa, NJ, 2007;
- Robson P. J., Drug Test. Anal. 2014, 6, 24–30; - PubMed
- Mechoulam R., Hanus L. O., Pertwee R., Howlett A. C., Nat. Rev. Neurosci. 2014, 15, 757–764; - PubMed
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