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Total Synthesis and Structural Revision of (±)-Mauritamide B
Hirozumi, Ryosuke ; Kudo, Yuta ; Cho, Yuko ; Konoki, Keiichi ; Yotsu-Yamashita, Mari ;
Abstract: Mauritamide B (1a) is a taurine-connected cyclic guanidino-bromopyrrole alkaloid originally isolated from the marine sponge Agelas linnaei. To date, the total synthesis of taurine-connected guanidino-bromopyrrole alkaloids, including this compound, has not yet been reported. Herein, a total synthesis of (±)-mauritamide B (1b) was achieved by oxidation of 2-aminoimidazole of dihydro-sventrin (10) using activated carbon and air in the presence of taurine. The synthetic precursor of 10, 4-(3-aminopropyl)-2-aminoimidazole (22), was synthesized via our original route. The NMR data of the obtained product agreed with that reported for mauritamide B (1a). However, a detailed analysis of the NMR data of synthetic (±)-mauritamide B (1b) including 11H−15N HSQC spectrum revealed the need for a structural revision of the reported structure for mauritamide B (1b).
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CAS No. : | 152120-54-2 |
Formula : | C14H22N4O4 |
M.W : | 310.35 |
SMILES Code : | C(=O)(OC(C)(C)C)NC([N]1C=CC=N1)=NC(OC(C)(C)C)=O |
MDL No. : | MFCD01075122 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73.8% | Step F-2: tert-Butyl ( tert-butoxycarbonyliminopyrazol-1- yl-methyl)carbamate [compound (H)]A tetrahydrofuran (100 ml) solution of the compound (50 g) obtained in Step B-I was added to a tetrahydrofuran (100 ml) suspension of 60% sodium hydride (9.99 g) over 1 hour while maintaining the temperature in the range of -5C to 00C. After the mixture was stirred for 30 minutes at the same temperature, a tetrahydrofuran (100 ml) solution of ditert-butyl dicarbonate (57.1 g) was added while maintaining the temperature from -5C to 00C. and then tetrahydrofuran (250 ml) was added. After the reaction solution was stirred for 2 hours under reflux, acetic acid (20.4 ml) was added at room temperature, and the solvent was distilled off under reduced pressure until the amount of solution became approximately 150 ml. A 5% aqueous sodium hydrogencarbonate solution (500 ml) was added to the resulting solution and the mixture was extracted with ethyl acetate (500 <n="81"/>ml). The organic layer was washed with water (150 ml), and the solvent was distilled off until the amount of solution became approximately 75 ml. Hexane (200 ml) was added to the residue at room temperature, and seed crystal was inoculated. After stirring the solution for 40 minutes under ice-cooling, crystals were filtered, washed with hexane (50 ml), and dried under reduced pressure to give the title compound (54.47 g, 73.8% yield) .1H NMR (CDCl3, 500 MHz): 1.49 (9H, s), 1.55 (9H, s), 6.41 (IH, dd, J = 1.5, 2.7 Hz), 7.62 (IH. dd, J = 0.7, 1.5 Hz), 8.30 (IH, dd, J = 0.7. 2.7 Hz), 8.93 (IH, brs) .13C NMR (CDCl3, 125 MHz): 28.1, 28.2, 81.4, 83.4, 109.8, 129.0. 139.2, 142.8. 149.4, 157.4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With acetic acid; In tetrahydrofuran; hexane; ethyl acetate; | Step 2 Manufacture of N,N'-bis-tert-butoxycarbonyl-pyrazole-1-carboxamidine To a suspension of sodium hydride (1.60 g, 40 mmol) in 70 ml tetrahydrofurane at 0C 2.10 g N-tert-butoxycarbonyl-pyrazole-1-carboxamidine (10 mmol) were added. The suspension was intensely agitated for 1 h at 0C. Then 4.5 g di-tert-butyl dicarbonate (20 mmol) were added and placed at room temperature and then gradually heated to the reflux. After one night under reflux the reaction medium was cooled to 0C; 2.3 ml acetic acid were added and the solution was agitated during 15 min. The organic phase was washed with 60 ml 5 % (w/w) sodium hydrogen carbonate, 60 ml of a saturated NaCl solution, dried over magnesium sulfate and then evaporated to dryness. The obtained residue was purified by silica chromatography (gradient 5 to 15 % ethylacetate in hexane) to obtain 2.48 g of a white solid (8.0 mmol, yield=80 %). | |
Step 2: Preparation of di-tert-butyl [(Z)-1H-pyrazol-1-ylmethylylidene]biscarbamate A THF (50 mL) solution of <strong>[152120-61-1]tert-butyl (1H-pyrazol-1-ylcarbonoimidoyl)carbamate</strong> (17 g, 0.08 mol) was added to a THF (50 mL) suspension of 60% NaH (6.4 g, 0.16 mol) over 1 hr while maintaining the temperature in the range of -5 C.?0 C. Then Boc2O (34.6 g, 0.16 mol) in THF (60 mL) was added, and the mixture was stirred at 80 C. for 20 hrs. Acetic acid (10 mL) was added and stirred for 20 min. After removal of the volatiles, the residue was dissolved in EtOAc (200 mL) and the solution was washed with aq. NaHCO3 (100 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo to afford the title compound (17.5 g, 70% yield) as a yellow oil. The crude material was used in the next step. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | In N,N-dimethyl-formamide; at 20℃; for 1.0h; | A solution of (+/-)-<strong>[770-05-8]octopamine hydrochloride</strong> (500 mg, 2.89 mmol) and N,N'-bis(Boc)-lH-pyrazole-l-carboxamidine (1.13 g, 3.60 mmol) in DMF (1OmL) was stirred for 1 h at ambient temperatures. The reaction mixture was concentrated, and the residue was dissolved in EtOAc (60 mL). The solution was washed with 1 nu <n="26"/>KHSO4 (2 x 30 mL) and 5% Na2CO3 (30 mL). The organic layer was dried (Na2SO4), concentrated, and purified by flash chromatography (EtOAc/hexane 30/70 -> 50/50) to yield the title compound as a colorless solid (836 mg, 73%). 1H NMR (CDCl3, 600 MHz): delta 11.45 (bs, IH), 8.76 (s, IH), 7.15 (d, J= 8.4 Hz, 2H), 6.77 (d, J= 8.4 Hz, 2H), 6.52 (bs, IH), 4.81-4.78 (m, IH), 3.66-3.50 (m, 2H), 1.51 (s, 9H), 1.49 (s, 9H); 13C NMR (CDCl3, 150 MHz): delta 162.86, 157.52, 156.04, 153.19, 133.52, 127.34, 115.65, 83.83, 80.07, 73.95, 49.49, 28.41, 28.26. MS (ESI): 396.4 (M + H, 100), 340.3 (M + H - tBu, 15). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83.9% | With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 2.66667h;Product distribution / selectivity; | (Example 8)Synthesis of tert-butyl (tert-butoxycarbonyliminopyrazol- 1-yl-methyl)carbamate [compound (H)]Step F-I: N,N-dimethylformamide (350 ml) and N. N- diisopropyl ethylamine (125 ml) were added to tert- butyl( iminopyrazol-1-yl-methyl)carbamate lH-pyrazole-1- <n="80"/>carboxamidine hydrochloride (100 g) , and then a N.N- dimethylformamide (50 ml) solution of ditert-butyl dicarbonate (152 g) was added over 40 minutes at room temperature. After the mixture was stirred for 2 hours at the same temperature, water (500 ml) was added, the mixture was extracted with toluene (500 ml), and organic layer 1 and aqueous layer 1 were separated. Organic layer 1 was further washed twice with water (300 ml), and organic layer 2 was separated. Aqueous layer 1 was extracted with toluene (500 ml), and organic layer 3 was separated. Organic layer 2 and organic layer 3 were combined, and the solvent was distilled off under reduced pressure until the amount of the solution became approximately 300 ml. Hexane (500 ml) was added to the resulting solution at room temperature, the mixture was stirred for 30 minutes, followed by stirring for 30 minutes under ice-cooling, and then crystals were filtered. The crystals were washed with hexane (100 ml), and then dried under reduced pressure to give the title compound (120.3 g. 83.9% yield) . |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81.4% | With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 1.0h; | 4-(2-Amino-1-hydroxyethyl)phenol hydrochloride (0.493 g, 2.6 mmol), was dissolved in dry DMF (10.0 mL) then successively treated with N,N-diisopropylethylamine (645 muL, 3.6 mmol) and N,N'-di-Boc-1H-pyrazole-1-carboxamidine (1.15 g, 3.7 mmol), and the resulting solution stirred 1 h at ambient temperature. All volatiles were then removed in vacuo and the residue dissolved in EtOAc with transfer to a separatory funnel. The EtOAc solution was exhaustively washed with dilute aqueous solutions of KHSO4 and Na2CO3 then dried over Na2SO4, filtered and concentrated in vacuo. Purification by chromatography on silica using a step gradient from 7:3 hexanes/EtOAc to 1 : 1 hexanes/EtOAc afforded the title compound as a white solid (0.837 g, 2.12 mmol; 81.4%). |
Tags: N,N'-Di-Boc-1H-pyrazole-1-carboximidamide | Pyrazoles | Amines | Esters | Carbamates | Organic Building Blocks | Heterocyclic Building Blocks | 152120-54-2
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