6790-63-2

Basic information

• Product Name: (3S)-7-Bromo-2,3,3a,8b-tetrahydro-3,3aβ,6,8bβ-tetramethyl-1H-cyclopenta[b]benzofuran
• Synonyms: (3S)-7-Bromo-2,3,3a,8b-tetrahydro-3,3aβ,6,8bβ-tetramethyl-1H-cyclopenta[b]benzofuran;Aplysin
• CAS NO: 6790-63-2
• Molecular Formula: C₁₅H₁₉BrO
• Molecular Weight: 295.21476
• Mol File: 6790-63-2.mol
• Article Data: 7

Chemical Properties

• Boiling Point: 335.1°Cat760mmHg
• Flash Point: 131.7°C
• Appearance: /
• Density: 1.307g/cm³
• Vapor Pressure: 0.000239mmHg at 25°C
• Refractive Index: 1.567
• CAS DataBase Reference: (3S)-7-Bromo-2,3,3a,8b-tetrahydro-3,3aβ,6,8bβ-tetramethyl-1H-cyclopenta[b]benzofuran(CAS DataBase Reference)
• NIST Chemistry Reference: (3S)-7-Bromo-2,3,3a,8b-tetrahydro-3,3aβ,6,8bβ-tetramethyl-1H-cyclopenta[b]benzofuran(6790-63-2)
• EPA Substance Registry System: (3S)-7-Bromo-2,3,3a,8b-tetrahydro-3,3aβ,6,8bβ-tetramethyl-1H-cyclopenta[b]benzofuran(6790-63-2)

Safety Data

• Hazardous Substances Data: 6790-63-2(Hazardous Substances Data)

Usage

General Description

"(3S)-7-Bromo-2,3,3a,8b-tetrahydro-3,3aβ,6,8bβ-tetramethyl-1H-cyclopenta[b]benzofuran" is a complex organic compound with multiple functional groups including bromine, methyl, and a fused cyclopenta[b]benzofuran ring structure. The compound's stereochemistry is specified by its (3S), αβ, αβ configuration. Its precise physical and chemical properties, such as its melting point, boiling point, polarity, solubility, and reactivity would be determined by the specific arrangement and interactions of its atoms and functional groups. Unfortunately, its specific uses, natural occurrence, or synthesis have not been widely reported in scientific literature. (3S)-7-Bromo-2,3,3a,8b-tetrahydro-3,3aβ,6,8bβ-tetramethyl-1H-cyclopenta[b]benzofuran, like others of its kind, may be researched and synthesized for various purposes in the field of organic chemistry or materials science.

InChI:InChI=1/C15H19BrO/c1-9-7-13-11(8-12(9)16)14(3)6-5-10(2)15(14,4)17-13/h7-8,10H,5-6H2,1-4H3

Synthetic route

(-)-Debromoaplysin (23444-68-0) → (-)-Aplysin (6790-63-2)

Conditions	Yield
With N-Bromosuccinimide In tetrachloromethane Heating;	87%
With bromine; sodium hydrogencarbonate In chloroform for 0.166667h; Ambient temperature;	84%
With bromine In chloroform at 0 - 20℃; for 0.166667h;	81%
With bromine; sodium carbonate In hexane for 0.0333333h;

laurinterol (10539-87-4) → (-)-Aplysin (6790-63-2)

Conditions	Yield
With hydrogen bromide In diethyl ether at 20℃; for 0.25h;

(3aS,8bS)-(-)-3a,8b-Dihydro-3,3a,6,8b-tetramethyl-1H-cyclopentabenzofuran (73307-78-5) → (-)-Aplysin (6790-63-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 79 percent / H2 / PtO2 / ethanol / 3 h / Ambient temperature 2: 84 percent / NaHCO3, Br2 / CHCl3 / 0.17 h / Ambient temperature View Scheme
Multi-step reaction with 2 steps 1: 83 percent / H2 / PtO2 / ethanol 2: 87 percent / N-bromosuccinimide / CCl4 / Heating View Scheme
Multi-step reaction with 2 steps 1: 69 percent / H2 / Adams's catalyst / ethanol / 2 h 2: Br2, anhydrous sodium carbonate / hexane / 0.03 h View Scheme

1-(methoxymethoxy)-3-methylbenzene (57234-27-2) → (-)-Aplysin (6790-63-2)

Conditions	Yield
Multi-step reaction with 9 steps 2: 90.5 percent / NaH / diethyl ether; dimethylformamide / 0.5 h 3: 37 percent / 1.) n-Butyllithium / diethyl ether / 1.) 15 min, 0 deg C, 2.) 10 min 4: 52 percent / KOH / methanol / 84 h / Heating 5: PCl3 / diethyl ether / 0.17 h 6: 96 percent / diethyl ether 7: 41 percent / Triphenylphosphine / (Ph3P)3RhCl / toluene; various solvent(s) / 120 h / Heating 8: 69 percent / H2 / Adams's catalyst / ethanol / 2 h 9: Br2, anhydrous sodium carbonate / hexane / 0.03 h View Scheme
Multi-step reaction with 9 steps 2: 90.5 percent / NaH / diethyl ether; dimethylformamide / 0.5 h 3: 37 percent / 1.) n-Butyllithium / diethyl ether / 1.) 15 min, 0 deg C, 2.) 10 min 4: 52 percent / KOH / methanol / 84 h / Heating 5: PBr3 / diethyl ether / 1 h 6: diethyl ether / 1 h 7: 41 percent / Triphenylphosphine / (Ph3P)3RhCl / toluene; various solvent(s) / 120 h / Heating 8: 69 percent / H2 / Adams's catalyst / ethanol / 2 h 9: Br2, anhydrous sodium carbonate / hexane / 0.03 h View Scheme

2-bromo-5-methylphenol (14847-51-9) → (-)-Aplysin (6790-63-2)

Conditions	Yield
Multi-step reaction with 8 steps 1: 90.5 percent / NaH / diethyl ether; dimethylformamide / 0.5 h 2: 37 percent / 1.) n-Butyllithium / diethyl ether / 1.) 15 min, 0 deg C, 2.) 10 min 3: 52 percent / KOH / methanol / 84 h / Heating 4: PCl3 / diethyl ether / 0.17 h 5: 96 percent / diethyl ether 6: 41 percent / Triphenylphosphine / (Ph3P)3RhCl / toluene; various solvent(s) / 120 h / Heating 7: 69 percent / H2 / Adams's catalyst / ethanol / 2 h 8: Br2, anhydrous sodium carbonate / hexane / 0.03 h View Scheme
Multi-step reaction with 8 steps 1: 90.5 percent / NaH / diethyl ether; dimethylformamide / 0.5 h 2: 37 percent / 1.) n-Butyllithium / diethyl ether / 1.) 15 min, 0 deg C, 2.) 10 min 3: 52 percent / KOH / methanol / 84 h / Heating 4: PBr3 / diethyl ether / 1 h 5: diethyl ether / 1 h 6: 41 percent / Triphenylphosphine / (Ph3P)3RhCl / toluene; various solvent(s) / 120 h / Heating 7: 69 percent / H2 / Adams's catalyst / ethanol / 2 h 8: Br2, anhydrous sodium carbonate / hexane / 0.03 h View Scheme

(-)-3-Methylphenyl(Isopinocampheyloxy)methyl Ether (73286-60-9) → (-)-Aplysin (6790-63-2)

Conditions	Yield
Multi-step reaction with 7 steps 1: 1.) tert-Butyllithium, TMEDA / 1.) Pentan, room temp., 0.5 h, 2.) 0 deg C, ether, 15 min 2: 52 percent / KOH / methanol / 84 h / Heating 3: PCl3 / diethyl ether / 0.17 h 4: 96 percent / diethyl ether 5: 41 percent / Triphenylphosphine / (Ph3P)3RhCl / toluene; various solvent(s) / 120 h / Heating 6: 69 percent / H2 / Adams's catalyst / ethanol / 2 h 7: Br2, anhydrous sodium carbonate / hexane / 0.03 h View Scheme
Multi-step reaction with 7 steps 1: 1.) tert-Butyllithium, TMEDA / 1.) Pentan, room temp., 0.5 h, 2.) 0 deg C, ether, 15 min 2: 52 percent / KOH / methanol / 84 h / Heating 3: PBr3 / diethyl ether / 1 h 4: diethyl ether / 1 h 5: 41 percent / Triphenylphosphine / (Ph3P)3RhCl / toluene; various solvent(s) / 120 h / Heating 6: 69 percent / H2 / Adams's catalyst / ethanol / 2 h 7: Br2, anhydrous sodium carbonate / hexane / 0.03 h View Scheme

(-)-2-Bromo-5-methylphenyl (Isopinocampheyloxy)methyl Ether (73286-62-1) → (-)-Aplysin (6790-63-2)

Conditions	Yield
Multi-step reaction with 7 steps 1: 37 percent / 1.) n-Butyllithium / diethyl ether / 1.) 15 min, 0 deg C, 2.) 10 min 2: 52 percent / KOH / methanol / 84 h / Heating 3: PCl3 / diethyl ether / 0.17 h 4: 96 percent / diethyl ether 5: 41 percent / Triphenylphosphine / (Ph3P)3RhCl / toluene; various solvent(s) / 120 h / Heating 6: 69 percent / H2 / Adams's catalyst / ethanol / 2 h 7: Br2, anhydrous sodium carbonate / hexane / 0.03 h View Scheme
Multi-step reaction with 7 steps 1: 37 percent / 1.) n-Butyllithium / diethyl ether / 1.) 15 min, 0 deg C, 2.) 10 min 2: 52 percent / KOH / methanol / 84 h / Heating 3: PBr3 / diethyl ether / 1 h 4: diethyl ether / 1 h 5: 41 percent / Triphenylphosphine / (Ph3P)3RhCl / toluene; various solvent(s) / 120 h / Heating 6: 69 percent / H2 / Adams's catalyst / ethanol / 2 h 7: Br2, anhydrous sodium carbonate / hexane / 0.03 h View Scheme

(-)-8b-Hydroxy-3a,8b-dihydro-3,3a,6-trimethyl-3H-cyclopentabenzofuran (73307-73-0) → (-)-Aplysin (6790-63-2)

Conditions	Yield
Multi-step reaction with 5 steps 1: PCl3 / diethyl ether / 0.17 h 2: 96 percent / diethyl ether 3: 41 percent / Triphenylphosphine / (Ph3P)3RhCl / toluene; various solvent(s) / 120 h / Heating 4: 69 percent / H2 / Adams's catalyst / ethanol / 2 h 5: Br2, anhydrous sodium carbonate / hexane / 0.03 h View Scheme
Multi-step reaction with 5 steps 1: PBr3 / diethyl ether / 1 h 2: diethyl ether / 1 h 3: 41 percent / Triphenylphosphine / (Ph3P)3RhCl / toluene; various solvent(s) / 120 h / Heating 4: 69 percent / H2 / Adams's catalyst / ethanol / 2 h 5: Br2, anhydrous sodium carbonate / hexane / 0.03 h View Scheme

(1R,4R,5R)-5-Chloro-4,5-dimethyl-1-[4-methyl-2-((1R,2R,3R,5S)-2,6,6-trimethyl-bicyclo[3.1.1]hept-3-yloxymethoxy)-phenyl]-cyclopent-2-enol (73286-61-0) → (-)-Aplysin (6790-63-2)

Conditions	Yield
Multi-step reaction with 6 steps 1: 52 percent / KOH / methanol / 84 h / Heating 2: PCl3 / diethyl ether / 0.17 h 3: 96 percent / diethyl ether 4: 41 percent / Triphenylphosphine / (Ph3P)3RhCl / toluene; various solvent(s) / 120 h / Heating 5: 69 percent / H2 / Adams's catalyst / ethanol / 2 h 6: Br2, anhydrous sodium carbonate / hexane / 0.03 h View Scheme
Multi-step reaction with 6 steps 1: 52 percent / KOH / methanol / 84 h / Heating 2: PBr3 / diethyl ether / 1 h 3: diethyl ether / 1 h 4: 41 percent / Triphenylphosphine / (Ph3P)3RhCl / toluene; various solvent(s) / 120 h / Heating 5: 69 percent / H2 / Adams's catalyst / ethanol / 2 h 6: Br2, anhydrous sodium carbonate / hexane / 0.03 h View Scheme

3-methyl-phenol (108-39-4) → (-)-Aplysin (6790-63-2)

Conditions	Yield
Multi-step reaction with 8 steps 1: 92 percent / NaH / diethyl ether; dimethylformamide / 0.17 h 2: 1.) tert-Butyllithium, TMEDA / 1.) Pentan, room temp., 0.5 h, 2.) 0 deg C, ether, 15 min 3: 52 percent / KOH / methanol / 84 h / Heating 4: PCl3 / diethyl ether / 0.17 h 5: 96 percent / diethyl ether 6: 41 percent / Triphenylphosphine / (Ph3P)3RhCl / toluene; various solvent(s) / 120 h / Heating 7: 69 percent / H2 / Adams's catalyst / ethanol / 2 h 8: Br2, anhydrous sodium carbonate / hexane / 0.03 h View Scheme
Multi-step reaction with 8 steps 1: 92 percent / NaH / diethyl ether; dimethylformamide / 0.17 h 2: 1.) tert-Butyllithium, TMEDA / 1.) Pentan, room temp., 0.5 h, 2.) 0 deg C, ether, 15 min 3: 52 percent / KOH / methanol / 84 h / Heating 4: PBr3 / diethyl ether / 1 h 5: diethyl ether / 1 h 6: 41 percent / Triphenylphosphine / (Ph3P)3RhCl / toluene; various solvent(s) / 120 h / Heating 7: 69 percent / H2 / Adams's catalyst / ethanol / 2 h 8: Br2, anhydrous sodium carbonate / hexane / 0.03 h View Scheme

(3S,3aR,8bS)-(-)-2,3,3a,8b-Tetrahydro-3-hydroxy-3,3a,6,8b-tetramethyl-1H-cyclopentabenzofuran (154800-88-1) → (-)-Aplysin (6790-63-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: 100 percent / POCl3, pyridine / 18 h / Ambient temperature 2: 79 percent / H2 / PtO2 / ethanol / 3 h / Ambient temperature 3: 84 percent / NaHCO3, Br2 / CHCl3 / 0.17 h / Ambient temperature View Scheme

(1S,3R)-3-(2-hydroxy-4-methylphenyl)-1,3-dimethyl-2-methylidenecyclopentanol (154699-13-5) → (-)-Aplysin (6790-63-2)

Conditions	Yield
Multi-step reaction with 4 steps 1: 88 percent / Hg(OCOCF3)2 / tetrahydrofuran / 2 h / Ambient temperature 2: 100 percent / POCl3, pyridine / 18 h / Ambient temperature 3: 79 percent / H2 / PtO2 / ethanol / 3 h / Ambient temperature 4: 84 percent / NaHCO3, Br2 / CHCl3 / 0.17 h / Ambient temperature View Scheme

(3R)-3-<2-(tert-Butyldimethylsiloxy)-4-methylphenyl>-1,3-dimethyl-2-methylidenecyclopentanol → (-)-Aplysin (6790-63-2)

Conditions	Yield
Multi-step reaction with 5 steps 1: 88 percent / n-Bu4N(1+)*F(1-) / tetrahydrofuran / 2 h / Ambient temperature 2: 88 percent / Hg(OCOCF3)2 / tetrahydrofuran / 2 h / Ambient temperature 3: 100 percent / POCl3, pyridine / 18 h / Ambient temperature 4: 79 percent / H2 / PtO2 / ethanol / 3 h / Ambient temperature 5: 84 percent / NaHCO3, Br2 / CHCl3 / 0.17 h / Ambient temperature View Scheme

(3R,3aS,8bR)-8b-Chloro-3,3a,6-trimethyl-3a,8b-dihydro-3H-benzo[b]cyclopenta[d]furan (73286-64-3) → (-)-Aplysin (6790-63-2)

Conditions	Yield
Multi-step reaction with 4 steps 1: 96 percent / diethyl ether 2: 41 percent / Triphenylphosphine / (Ph3P)3RhCl / toluene; various solvent(s) / 120 h / Heating 3: 69 percent / H2 / Adams's catalyst / ethanol / 2 h 4: Br2, anhydrous sodium carbonate / hexane / 0.03 h View Scheme

(3R,3aS,8bR)-8b-Bromo-3,3a,6-trimethyl-3a,8b-dihydro-3H-benzo[b]cyclopenta[d]furan (73286-63-2) → (-)-Aplysin (6790-63-2)

Conditions	Yield
Multi-step reaction with 4 steps 1: diethyl ether / 1 h 2: 41 percent / Triphenylphosphine / (Ph3P)3RhCl / toluene; various solvent(s) / 120 h / Heating 3: 69 percent / H2 / Adams's catalyst / ethanol / 2 h 4: Br2, anhydrous sodium carbonate / hexane / 0.03 h View Scheme

(-)-3,3a,8b-Trihydro-3,3a,6,8b-tetramethylcyclopentabenzofuran (73307-75-2) → (-)-Aplysin (6790-63-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: 41 percent / Triphenylphosphine / (Ph3P)3RhCl / toluene; various solvent(s) / 120 h / Heating 2: 69 percent / H2 / Adams's catalyst / ethanol / 2 h 3: Br2, anhydrous sodium carbonate / hexane / 0.03 h View Scheme

o-tolylhydrazine hydrochloride (635-26-7) → (-)-Aplysin (6790-63-2)

Conditions	Yield
Multi-step reaction with 9 steps 1: 1) pyridine, 2) conc. H2SO4, NaNO2 / 1) water, reflux, 2) 0 deg C 2: Li diisopropylamide / tetrahydrofuran 3: various solvent(s) / Heating 4: tetrahydrofuran 5: PCC / CH2Cl2 6: 60 percent / BBr3 / 1,2-dichloro-ethane / 80 °C 7: 1) i-Bu2AlH, 2) 10percent aq. HCl 8: 83 percent / H2 / PtO2 / ethanol 9: 87 percent / N-bromosuccinimide / CCl4 / Heating View Scheme

(3aS,4R,7S,7aR)-2-Methyl-2,3,3a,4,7,7a-hexahydro-4,7-methano-inden-1-one (139685-68-0) → (-)-Aplysin (6790-63-2)

Conditions	Yield
Multi-step reaction with 9 steps 1: 1) pyridine, 2) conc. H2SO4, NaNO2 / 1) water, reflux, 2) 0 deg C 2: Li diisopropylamide / tetrahydrofuran 3: various solvent(s) / Heating 4: tetrahydrofuran 5: PCC / CH2Cl2 6: 60 percent / BBr3 / 1,2-dichloro-ethane / 80 °C 7: 1) i-Bu2AlH, 2) 10percent aq. HCl 8: 83 percent / H2 / PtO2 / ethanol 9: 87 percent / N-bromosuccinimide / CCl4 / Heating View Scheme

(S)-5-(2-Methoxy-4-methyl-phenyl)-2,5-dimethyl-cyclopent-2-enone (139618-47-6) → (-)-Aplysin (6790-63-2)

Conditions	Yield
Multi-step reaction with 6 steps 1: tetrahydrofuran 2: PCC / CH2Cl2 3: 60 percent / BBr3 / 1,2-dichloro-ethane / 80 °C 4: 1) i-Bu2AlH, 2) 10percent aq. HCl 5: 83 percent / H2 / PtO2 / ethanol 6: 87 percent / N-bromosuccinimide / CCl4 / Heating View Scheme

(R)-4-(2-Hydroxy-4-methyl-phenyl)-2,3,4-trimethyl-cyclopent-2-enone (139618-50-1) → (-)-Aplysin (6790-63-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1) i-Bu2AlH, 2) 10percent aq. HCl 2: 83 percent / H2 / PtO2 / ethanol 3: 87 percent / N-bromosuccinimide / CCl4 / Heating View Scheme

(R)-4-(2-Methoxy-4-methyl-phenyl)-2,3,4-trimethyl-cyclopent-2-enone (139618-49-8) → (-)-Aplysin (6790-63-2)

Conditions	Yield
Multi-step reaction with 4 steps 1: 60 percent / BBr3 / 1,2-dichloro-ethane / 80 °C 2: 1) i-Bu2AlH, 2) 10percent aq. HCl 3: 83 percent / H2 / PtO2 / ethanol 4: 87 percent / N-bromosuccinimide / CCl4 / Heating View Scheme

(S)-5-(2-Methoxy-4-methyl-phenyl)-1,2,5-trimethyl-cyclopent-2-enol (139618-48-7, 139685-70-4) → (-)-Aplysin (6790-63-2)

Conditions	Yield
Multi-step reaction with 5 steps 1: PCC / CH2Cl2 2: 60 percent / BBr3 / 1,2-dichloro-ethane / 80 °C 3: 1) i-Bu2AlH, 2) 10percent aq. HCl 4: 83 percent / H2 / PtO2 / ethanol 5: 87 percent / N-bromosuccinimide / CCl4 / Heating View Scheme

(2S,3aS,4R,7S,7aR)-2-(2-Methoxy-4-methyl-phenyl)-2,7a-dimethyl-2,3,3a,4,7,7a-hexahydro-4,7-methano-inden-1-one (139618-46-5) → (-)-Aplysin (6790-63-2)

Conditions	Yield
Multi-step reaction with 7 steps 1: various solvent(s) / Heating 2: tetrahydrofuran 3: PCC / CH2Cl2 4: 60 percent / BBr3 / 1,2-dichloro-ethane / 80 °C 5: 1) i-Bu2AlH, 2) 10percent aq. HCl 6: 83 percent / H2 / PtO2 / ethanol 7: 87 percent / N-bromosuccinimide / CCl4 / Heating View Scheme

(2S,3aS,4R,7S,7aR)-2-(2-Methoxy-4-methyl-phenyl)-2-methyl-2,3,3a,4,7,7a-hexahydro-4,7-methano-inden-1-one (139618-44-3) → (-)-Aplysin (6790-63-2)

Conditions	Yield
Multi-step reaction with 8 steps 1: Li diisopropylamide / tetrahydrofuran 2: various solvent(s) / Heating 3: tetrahydrofuran 4: PCC / CH2Cl2 5: 60 percent / BBr3 / 1,2-dichloro-ethane / 80 °C 6: 1) i-Bu2AlH, 2) 10percent aq. HCl 7: 83 percent / H2 / PtO2 / ethanol 8: 87 percent / N-bromosuccinimide / CCl4 / Heating View Scheme

(R)-(+)-1-(2'-methoxy-4'-methylphenyl)ethanol (1344927-26-9) → (-)-Aplysin (6790-63-2)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: triethylamine / dichloromethane / 48 h / Reflux 2.1: N,N,N,N,-tetramethylethylenediamine; sec.-butyllithium / diethyl ether; hexane / 0.25 h / -78 °C / Inert atmosphere 2.2: 1 h / -78 °C / Inert atmosphere 3.1: tert.-butyl lithium / tetrahydrofuran / 0.5 h / -78 °C / UneV-irradiation 3.2: 2 h / -78 - -40 °C / Inert atmosphere 3.3: 1 h / -78 - 0 °C 4.1: Hoveyda-Grubbs catalyst second generation / toluene / 24 h / Reflux 5.1: trimethylsilyl iodide; ortho-cresol / dichloromethane / 20 °C 6.1: bromine / chloroform / 0.17 h / 0 - 20 °C View Scheme
Multi-step reaction with 6 steps 1.1: triethylamine / dichloromethane / 48 h / Reflux 2.1: N,N,N,N,-tetramethylethylenediamine; sec.-butyllithium / diethyl ether; hexane / 0.25 h / -78 °C / Inert atmosphere 2.2: 1 h / -78 °C / Inert atmosphere 3.1: tert.-butyl lithium / tetrahydrofuran / 0.5 h / -78 °C / UneV-irradiation 3.2: 2 h / -78 - -40 °C / Inert atmosphere 3.3: 1 h / -78 - 0 °C 4.1: Hoveyda-Grubbs catalyst second generation / toluene / 24 h / Reflux 5.1: trimethylsilyl iodide; 2,6-di-tert-butylphenol / dichloromethane / 20 °C 6.1: bromine / chloroform / 0.17 h / 0 - 20 °C View Scheme
Multi-step reaction with 6 steps 1.1: triethylamine / dichloromethane / 48 h / Reflux 2.1: N,N,N,N,-tetramethylethylenediamine; sec.-butyllithium / diethyl ether; hexane / 0.25 h / -78 °C / Inert atmosphere 2.2: 1 h / -78 °C / Inert atmosphere 3.1: tert.-butyl lithium / tetrahydrofuran / 0.5 h / -78 °C / UneV-irradiation 3.2: 2 h / -78 - -40 °C / Inert atmosphere 3.3: 1 h / -78 - 0 °C 4.1: Hoveyda-Grubbs catalyst second generation / toluene / 24 h / Reflux 5.1: trimethylsilyl iodide; 2,6-di-tert-butylphenol / dichloromethane / 24 h / -78 °C 6.1: bromine / chloroform / 0.17 h / 0 - 20 °C View Scheme

(R)-1-(2'-methoxy-4'-methylphenyl)ethyl diisopropylcarbamate (1394171-14-2) → (-)-Aplysin (6790-63-2)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: N,N,N,N,-tetramethylethylenediamine; sec.-butyllithium / diethyl ether; hexane / 0.25 h / -78 °C / Inert atmosphere 1.2: 1 h / -78 °C / Inert atmosphere 2.1: tert.-butyl lithium / tetrahydrofuran / 0.5 h / -78 °C / UneV-irradiation 2.2: 2 h / -78 - -40 °C / Inert atmosphere 2.3: 1 h / -78 - 0 °C 3.1: Hoveyda-Grubbs catalyst second generation / toluene / 24 h / Reflux 4.1: trimethylsilyl iodide; ortho-cresol / dichloromethane / 20 °C 5.1: bromine / chloroform / 0.17 h / 0 - 20 °C View Scheme
Multi-step reaction with 5 steps 1.1: N,N,N,N,-tetramethylethylenediamine; sec.-butyllithium / diethyl ether; hexane / 0.25 h / -78 °C / Inert atmosphere 1.2: 1 h / -78 °C / Inert atmosphere 2.1: tert.-butyl lithium / tetrahydrofuran / 0.5 h / -78 °C / UneV-irradiation 2.2: 2 h / -78 - -40 °C / Inert atmosphere 2.3: 1 h / -78 - 0 °C 3.1: Hoveyda-Grubbs catalyst second generation / toluene / 24 h / Reflux 4.1: trimethylsilyl iodide; 2,6-di-tert-butylphenol / dichloromethane / 20 °C 5.1: bromine / chloroform / 0.17 h / 0 - 20 °C View Scheme
Multi-step reaction with 5 steps 1.1: N,N,N,N,-tetramethylethylenediamine; sec.-butyllithium / diethyl ether; hexane / 0.25 h / -78 °C / Inert atmosphere 1.2: 1 h / -78 °C / Inert atmosphere 2.1: tert.-butyl lithium / tetrahydrofuran / 0.5 h / -78 °C / UneV-irradiation 2.2: 2 h / -78 - -40 °C / Inert atmosphere 2.3: 1 h / -78 - 0 °C 3.1: Hoveyda-Grubbs catalyst second generation / toluene / 24 h / Reflux 4.1: trimethylsilyl iodide; 2,6-di-tert-butylphenol / dichloromethane / 24 h / -78 °C 5.1: bromine / chloroform / 0.17 h / 0 - 20 °C View Scheme

(R)-2-methoxy-4-methyl-1-(1,2,3-trimethylcyclopent-2-enyl)benzene (1394171-12-0) → (-)-Aplysin (6790-63-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: trimethylsilyl iodide; 2,6-di-tert-butylphenol / dichloromethane / 20 °C 2: bromine / chloroform / 0.17 h / 0 - 20 °C View Scheme
Multi-step reaction with 2 steps 1: trimethylsilyl iodide; 2,6-di-tert-butylphenol / dichloromethane / 24 h / -78 °C 2: bromine / chloroform / 0.17 h / 0 - 20 °C View Scheme
Multi-step reaction with 2 steps 1: trimethylsilyl iodide; ortho-cresol / dichloromethane / 20 °C 2: bromine / chloroform / 0.17 h / 0 - 20 °C View Scheme

(R)-2-(2-(2-methoxy-4-methylphenyl)-5-methylhex-5-en-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1394171-13-1) → (-)-Aplysin (6790-63-2)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: tert.-butyl lithium / tetrahydrofuran / 0.5 h / -78 °C / UneV-irradiation 1.2: 2 h / -78 - -40 °C / Inert atmosphere 1.3: 1 h / -78 - 0 °C 2.1: Hoveyda-Grubbs catalyst second generation / toluene / 24 h / Reflux 3.1: trimethylsilyl iodide; ortho-cresol / dichloromethane / 20 °C 4.1: bromine / chloroform / 0.17 h / 0 - 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: tert.-butyl lithium / tetrahydrofuran / 0.5 h / -78 °C / UneV-irradiation 1.2: 2 h / -78 - -40 °C / Inert atmosphere 1.3: 1 h / -78 - 0 °C 2.1: Hoveyda-Grubbs catalyst second generation / toluene / 24 h / Reflux 3.1: trimethylsilyl iodide; 2,6-di-tert-butylphenol / dichloromethane / 20 °C 4.1: bromine / chloroform / 0.17 h / 0 - 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: tert.-butyl lithium / tetrahydrofuran / 0.5 h / -78 °C / UneV-irradiation 1.2: 2 h / -78 - -40 °C / Inert atmosphere 1.3: 1 h / -78 - 0 °C 2.1: Hoveyda-Grubbs catalyst second generation / toluene / 24 h / Reflux 3.1: trimethylsilyl iodide; 2,6-di-tert-butylphenol / dichloromethane / 24 h / -78 °C 4.1: bromine / chloroform / 0.17 h / 0 - 20 °C View Scheme

(R)-2-methoxy-4-methyl-1-(2,3,6-trimethylhepta-1,6-dien-3-yl)benzene (1394171-15-3) → (-)-Aplysin (6790-63-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: Hoveyda-Grubbs catalyst second generation / toluene / 24 h / Reflux 2: trimethylsilyl iodide; 2,6-di-tert-butylphenol / dichloromethane / 20 °C 3: bromine / chloroform / 0.17 h / 0 - 20 °C View Scheme
Multi-step reaction with 3 steps 1: Hoveyda-Grubbs catalyst second generation / toluene / 24 h / Reflux 2: trimethylsilyl iodide; 2,6-di-tert-butylphenol / dichloromethane / 24 h / -78 °C 3: bromine / chloroform / 0.17 h / 0 - 20 °C View Scheme
Multi-step reaction with 3 steps 1: Hoveyda-Grubbs catalyst second generation / toluene / 24 h / Reflux 2: trimethylsilyl iodide; ortho-cresol / dichloromethane / 20 °C 3: bromine / chloroform / 0.17 h / 0 - 20 °C View Scheme

4'-hydroxy-2'-methylacetophenone (6921-64-8) → (-)-Aplysin (6790-63-2)

Conditions	Yield
Multi-step reaction with 8 steps 1.1: potassium hydroxide / acetone / 16 h / 20 °C 2.1: [N-[(1R,2R)-2-(amino-κN)-1,2-diphenylethyl]-4-methylbenzenesulfonamidato-κN]chloro[(1,2, 3,4,5,6-η)-1-methyl-4-(1-methylethyl)benzene]-ruthenium; formic acid; triethylamine / 96 h / 20 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 48 h / Reflux 4.1: N,N,N,N,-tetramethylethylenediamine; sec.-butyllithium / diethyl ether; hexane / 0.25 h / -78 °C / Inert atmosphere 4.2: 1 h / -78 °C / Inert atmosphere 5.1: tert.-butyl lithium / tetrahydrofuran / 0.5 h / -78 °C / UneV-irradiation 5.2: 2 h / -78 - -40 °C / Inert atmosphere 5.3: 1 h / -78 - 0 °C 6.1: Hoveyda-Grubbs catalyst second generation / toluene / 24 h / Reflux 7.1: trimethylsilyl iodide; ortho-cresol / dichloromethane / 20 °C 8.1: bromine / chloroform / 0.17 h / 0 - 20 °C View Scheme
Multi-step reaction with 8 steps 1.1: potassium hydroxide / acetone / 16 h / 20 °C 2.1: [N-[(1R,2R)-2-(amino-κN)-1,2-diphenylethyl]-4-methylbenzenesulfonamidato-κN]chloro[(1,2, 3,4,5,6-η)-1-methyl-4-(1-methylethyl)benzene]-ruthenium; formic acid; triethylamine / 96 h / 20 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 48 h / Reflux 4.1: N,N,N,N,-tetramethylethylenediamine; sec.-butyllithium / diethyl ether; hexane / 0.25 h / -78 °C / Inert atmosphere 4.2: 1 h / -78 °C / Inert atmosphere 5.1: tert.-butyl lithium / tetrahydrofuran / 0.5 h / -78 °C / UneV-irradiation 5.2: 2 h / -78 - -40 °C / Inert atmosphere 5.3: 1 h / -78 - 0 °C 6.1: Hoveyda-Grubbs catalyst second generation / toluene / 24 h / Reflux 7.1: trimethylsilyl iodide; 2,6-di-tert-butylphenol / dichloromethane / 20 °C 8.1: bromine / chloroform / 0.17 h / 0 - 20 °C View Scheme
Multi-step reaction with 8 steps 1.1: potassium hydroxide / acetone / 16 h / 20 °C 2.1: [N-[(1R,2R)-2-(amino-κN)-1,2-diphenylethyl]-4-methylbenzenesulfonamidato-κN]chloro[(1,2, 3,4,5,6-η)-1-methyl-4-(1-methylethyl)benzene]-ruthenium; formic acid; triethylamine / 96 h / 20 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 48 h / Reflux 4.1: N,N,N,N,-tetramethylethylenediamine; sec.-butyllithium / diethyl ether; hexane / 0.25 h / -78 °C / Inert atmosphere 4.2: 1 h / -78 °C / Inert atmosphere 5.1: tert.-butyl lithium / tetrahydrofuran / 0.5 h / -78 °C / UneV-irradiation 5.2: 2 h / -78 - -40 °C / Inert atmosphere 5.3: 1 h / -78 - 0 °C 6.1: Hoveyda-Grubbs catalyst second generation / toluene / 24 h / Reflux 7.1: trimethylsilyl iodide; 2,6-di-tert-butylphenol / dichloromethane / 24 h / -78 °C 8.1: bromine / chloroform / 0.17 h / 0 - 20 °C View Scheme

Upstream product

• 23444-68-0 (-)-Debromoaplysin 
• 73307-78-5 (3aS,8bS)-(-)-3a,8b-Dihydro-3,3a,6,8b-tetramethyl-1H-cyclopentabenzofuran 
• 154800-88-1 (3S,3aR,8bS)-(-)-2,3,3a,8b-Tetrahydro-3-hydroxy-3,3a,6,8b-tetramethyl-1H-cyclopentabenzofuran 
• 154699-13-5 (1S,3R)-3-(2-hydroxy-4-methylphenyl)-1,3-dimethyl-2-methylidenecyclopentanol 
• 635-26-7 o-tolylhydrazine hydrochloride 
• 139685-68-0 (3aS,4R,7S,7aR)-2-Methyl-2,3,3a,4,7,7a-hexahydro-4,7-methano-inden-1-one 
• 139618-47-6 (S)-5-(2-Methoxy-4-methyl-phenyl)-2,5-dimethyl-cyclopent-2-enone 
• 139618-50-1 (R)-4-(2-Hydroxy-4-methyl-phenyl)-2,3,4-trimethyl-cyclopent-2-enone 
• 139618-49-8 (R)-4-(2-Methoxy-4-methyl-phenyl)-2,3,4-trimethyl-cyclopent-2-enone 
• 139618-48-7 (S)-5-(2-Methoxy-4-methyl-phenyl)-1,2,5-trimethyl-cyclopent-2-enol 
• 139618-46-5 (2S,3aS,4R,7S,7aR)-2-(2-Methoxy-4-methyl-phenyl)-2,7a-dimethyl-2,3,3a,4,7,7a-hexahydro-4,7-methano-inden-1-one 
• 139618-44-3 (2S,3aS,4R,7S,7aR)-2-(2-Methoxy-4-methyl-phenyl)-2-methyl-2,3,3a,4,7,7a-hexahydro-4,7-methano-inden-1-one 
• 57234-27-2 1-(methoxymethoxy)-3-methylbenzene 
• 14847-51-9 2-bromo-5-methylphenol 

Relevant articles and documents

Anti-acanthamoeba activity of brominated sesquiterpenes from laurencia johnstonii

Focused on our interest to develop novel antiparasistic agents, the present study was aimed to evaluate the biological activity of an extract of Laurencia johnstonii collected in Baja California Sur, Mexico, against an Acantamoeba castellanii Neff strain. Bioassay-guided fractionation allowed us to identify the amoebicidal diastereoisomers α-bromocuparane (4) and α-isobromocuparane (5). Furthermore, bromination of the inactive laurinterol (1) and isolaurinterol (2) yielded four halogenated derivatives, (6)-(9), which improved the activity of the natural sesquiterpenes. Among them, the most active compound was 3α-bromojohnstane (7), a sesquiterpene derivative which possesses a novel carbon skeleton johnstane.

A Remarkable Substituent Effect on the Enantioselectivity of Tandem Asymmetric Epoxidation and Enantiospecific Ring Expansion of Cyclopropylidene Alcohols: A New Enantiocontrolled Synthesis of (-)-Debromoaplysin and (-)-Aplysin

A remarkable substituent effect by the tert-butyldimethylsiloxy group on the enantioselectivity of the tandem asymmetric epoxidation and enantiospecific ring expansion of 2--2-cyclopropylideneethanol (18), affording (S)-(-)-2--2-hydroxymethylcyclobutanone (21) in high yield and high enantiomeric excess, was observed.This enabled us to accomplish a concise and highly enantioselective total synthesis of (-)-debromoaplysin (2) and (-)-aplysin (1), providing a new and general strategy for the enantioselective synthesis of biologically important substances having the dihydrobenzofuran framework.

The rearrangement of some cyclopentanone-aryloximes: Synthesis of (±)-aplysin, (±)-filiformin and of their debromo analogues

Upon acid catalyzed rearrangement after Sheradsky, the aryloximes A gave the tricyclic aminals C, which suffered hydrolysis to lactols E. The unique alcohol 29 was then prepared through a highly stereoselective equilibration-reductive alkylation of the epimeric mixture of lactols 22a,b. Two routes, one of which was stereospecific, allowed cyclization of 29 to (±)-aplysin 34. The yield was 2.5 % from oximes 2a,b. The isomeric epi-aplysin 35 and filiformin 36 were also obtained from 29. The debromo analogues 37,38 and 39 and their trideutero derivatives 41,42 and 43 were synthesized along similar line and allowed unequivocal structure elucidation by NMR spectroscopy.