2-oxopropanoic acid

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:7.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 14 mL (0.2 mol) of pyruvic acid and 80 mL of triethylorthoformate at 10° C. was added 1 mL of concentrated sulfuric acid. The resulting mixture was stirred at 5-10° C. for 1 h and then diluted with 200 mL of dichloromethane. The organic solution was washed successively with water (3×80 mL) and saturated sodium chloride solution (80 mL) and then dried over anhydrous sodium sulfate. The mixture was filtered and then concentrated to give a quantitative yield of 2,2-diethoxypropionic acid as an oil. 1H NMR (CDCl3, 400 MHz): δ 1.30 (t, 6H), 1.61 (s, 3H), 3.57 (q, 4H), 8.62 (s, 1H). The acid form was quantitatively converted to its cesium salt by dissolving the acid in water (25 mL) followed by treatment with an equimolar quantity of cesium carbonate, and then lyophilization. 1H NMR (D2O, 400 MHz): δ 0.98 (t, 6H), 1.28 (s, 3H), 3.22 (q, 2H), 3.47 (q, 2H). The organic solution was washed successively with water (3×80 mL) and saturated sodium chloride solution (80 mL) dried over anhydrous sodium sulfate The mixture was filtered concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a boiling solution of 2-thiophenecarboxaldehyde (1.22 ml), pyruvic acid (0.904 ml) and 50 ml absolute EtOH is added dropwise a solution of 3,4-dimethoxyaniline (2.00 g) in 100 ml EtOH. The mixture is refluxed for approximately 4 hours, then stored at room temperature overnight. The greenish-yellow precipitate is collected by filtration, washed with fresh EtOH then with ether and allowed to air dry to obtain 2-(thien-2-yl)-4-carboxy-6,7-dimethoxyquinoline m.p. 260°-263° C.). The mixture is refluxed for approximately 4 hours The greenish-yellow precipitate is collected by filtration washed with fresh EtOH to air dry

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of 2-methoxybenzamide in 1,2-di-chloroethane (24.5 ml/g) is brought to reflux in the presence of 3 equivalents of freshly distilled pyruvic acid in a round-bottomed flask surmounted by a system which makes it possible to remove the water formed during the reaction. When the formation of water has finished 15 (approximately 7 hours), the reaction mixture is left at room temperature. After filtering off the insoluble materials, the filtrate is extracted with an aqueous sodium bicarbonate solution. The combined aqueous phases are extracted with dichloromethane and then acidified with hydrochloric acid. The precipitate formed is filtered off, dried and then taken up in ethyl acetate. After filtering off the insoluble material, the filtrate is concentrated under vacuum, dissolved in dichloromethane and then precipitated with heptane, thus providing pure N-(2-methoxybenzoyl)dehydroalanine. (Nonoptimized yield 8.5%). to remove the water formed during the reaction 15 (approximately 7 hours) the reaction mixture is left at room temperature After filtering off the insoluble materials the filtrate is extracted with an aqueous sodium bicarbonate solution The combined aqueous phases are extracted with dichloromethane The precipitate formed is filtered off dried After filtering off the insoluble material the filtrate is concentrated under vacuum dissolved in dichloromethane precipitated with heptane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Nature's utilization of a potential counterpart in the formation of zoanthoxanthins forms a basis of our biogenic hypothesis and involves the introduction of a two-carbon unit (or equivalent) to the C3N3 heterocycle as the penultimate step prior to dimerization. Incorporation of this hypothetical two-carbon entity could be accomplished by a hitherto unknown hydroxyalkylation of 2-aminoimidazole with a suitably functionalized two-carbon aldehyde or pyruvic acid. To test this hypothesis, 2-aminoimidazole sulfate was heated at 95°-100° C. with chloroacetaldehyde in concentrated hydrochloric acid for 24 hours. After basification to pH 12 and chromatography, parazoanthoxanthin A (1A) (41% yield) and pseudozoanthoxanthin A (2A) (7% yield) were obtained. Most importantly, moderate amounts of (1A) and (2A) were produced at room temperature after 7 days. Under acidic conditions, the proton serves as a natural protecting group for nitrogen as well as catalyst for hydroxyalkylation and subsequent dimerization. Similar results were seen with pyruvic acid and the more highly reduced two-carbon unit, acetaldehyde, but with less efficiency. Reactions involving pyruvic acid and acetaldehyde were carried out in 37% HCl between 95°-100° C. for 24 hours. Acetaldehyde gave a 25% yield of parazoanthoxanthin A and pseudozoanthoxanthin A in a 3:1 ratio, respectively, whereas pyruvic acid produced a 15% yield of parazoanthoxanthin A and trace amounts of pseudozoanthoxanthin A. With these reactants, decarboxylation and/or final oxidation to the ten-electron azulene ring system is necessary (the oxidation is probably assisted by sulfuric acid derived from the commercial starting material, 2-aminoimidazole sulfate) and most likely accounts for the lower overall yields. At 23° C., the reaction between (AI) and acetaldehyde afforded products (12) (ref. 29); and (14) [Compound 5.2HCl, colorless solid, mp 240° C. (dec); 1H NMR (DMSO-D6, 300 MHz) δ ppm: 1.51 (d, 7.2 Hz, 3H), 3.97 (q, 7.2 Hz, 1H), 6.65 (s, 2H), 7.37 (s, 4H, exchanged with D2O), 11.85 (s, 2H, exchanged with D2O), 12.37 (s, 2H, exchanged with D2O); 13C NMR (free-base, DMSO-D6, 75.1 MHz) δ ppm: 20.0 (q), 30.4 (d), 111.0 (d), 135.8 (s), 148.9 (s); IR (nujol) ν cm-1 : 3240, 3126, 1667; MS (CI, NH3) m/z 193 (MH+)] (10-40% yields); in addition to small amounts of zoanthoxanthins. Formation of (14) [Dimer (14), when heated at 95°-100° C. with 1 eq. of acetaldehyde produced parazoanthoxanthin A], a precursor to parazoanthoxanthin A (1A), can be explained by dehydration of (12) to intermediate (B) followed by C-attack of the imidazole to the exocyclic double bond. Intermediate (14) could next undergo hydroxyalkylation with acetaldehyde followed by dehydration, cyclization, and oxidation to give (1A). A similar process in which initial addition to the endocyclic double bond of species (B) would account for the formation of pseudozoanthoxanthin A (2A), although no intermediates have been isolated. Whether the actual biosynthetic pathway proceeds via a sequential series of hydroxyalkylation--dimerization--hydroxyalkylation events involving 2-aminoimidazole or by direct dimerization of two C5N3 monomers (ref. 28, 29) remains to be determined. Our results in combination with the known metabolic conversion of arginine to (AI) (ref. 31) suggest that the key biosynthetic intermediate is not a direct product of arginine metabolism but evolves from hydroxyalkylation of arginine derived (AI). One additional consideration is formation of the methylated metabolites of zoanthoxanthins since they comprise the majority of pigments isolated. The parent compounds (1A) and (2A) could serve as potential precursors in a late methylation scheme, or contrastly, an early, predimeric methylation process would yield N-methylated 2-aminoimidazoles as biogenic forerunners. ##STR27##

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirring solution of 5-(4-{[(2Z)-2-(5-ethylpyridin-2-yl)-2-(methoxyimino)ethyl]oxy}benzyl)-1,3-thiazolidine-2,4-dione (81 mg, 0.20 mmol; Supplier=Kalexsyn; Lot=1003-TTP-194) in 6M HCl (2 ml) and pyruvic acid (0.5 ml) was heated at 75° C. After 2 h at 75° C. HPLC showed reaction was complete. Neutralized with sat'd NaHCO3 and extracted with EtOAc. Extract dried (Na2SO4), filtered and evaporated in vacuo to give 45 mg (60%) pale yellow oil. 1H-NMR (DMSO-d6): δ12.02 (brs, 1H), 8.64 (s, 1H), 7.91 (m, 1H), 7.14 (d, J=8.5 Hz, 2H), 6.88 (d, J=8.5 Hz, 2H), 5.66 (s, 2H), 4.87 (dd, J=9.2, 4.3 Hz, 1H), 3.31 (m, 1H), 3.05 (dd, J=14.1, 9.1 Hz, 1H), 2.74 (q, J=7.7 Hz, 2H), 1.23 (t, J=7.7 Hz, 3H). HPLC (3.860 min., 100 area % @ 210 and 254 nm. MS (ESI—) for C19H18N2O4S m/z 371.3 (M+H)+: m/z 369.4 (M−H)− reaction Neutralized with sat'd NaHCO3 and extracted with EtOAc Extract dried (Na2SO4) filtered evaporated in vacuo to give 45 mg (60%) 3.860 min., 100 area

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of ethyl 4-amino-2-chloro-5-iodobenzoate (1.82 g, 5.59 mmol) in N,N-dimethylformamide (18 ml) under argon was admixed with pyruvic acid (1.27 ml, 18.2 mmol) and 1,4-diazabicyclo[2.2.2]octane, evacuated and flooded with argon. Then argon was passed through the solution for 5 min, and then palladium(II) acetate (68 mg, 0.30 mmol) was added and the mixture was heated to 100° C. for 2 h. The cooled solution was filtered through Celite and the filtercake was rinsed with ethyl acetate (100 ml). The filtrate (suspension) was washed with hydrochloric acid (2 M; 2×25 ml) and with water (2×25 ml), dried over sodium sulphate and filtered. The filtrate was concentrated to dryness under reduced pressure and gives a red-brown solid (1.93 g, approx. 51% product), which was used for the next step without further purification. evacuated The cooled solution was filtered through Celite the filtercake was rinsed with ethyl acetate (100 ml) The filtrate (suspension) was washed with hydrochloric acid (2 M; 2×25 ml) and with water (2×25 ml) dried over sodium sulphate filtered The filtrate was concentrated to dryness under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2.85 g. (0.01 mole) of 7-chloro-2-hydrazino-5-phenyl-3H-1,4-benzodiazepine in 100 ml. of tetrahydrofuran under nitrogen is added with stirring, 0.847 ml. (0.012 mole) of pyruvic acid. After 2.5 hours at room temperature and overnight at 0° C. 7-chloro-2-[(1-carboxyethylidene)hydrazino]-5-phenyl-3H-1,4-benzodiazepine is obtained. overnight at 0° C

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Nature's utilization of a potential counterpart in the formation of zoanthoxanthins forms a basis of our biogenic hypothesis and involves the introduction of a two-carbon unit (or equivalent) to the C3N3 heterocycle as the penultimate step prior to dimerization. Incorporation of this hypothetical two-carbon entity could be accomplished by a hitherto unknown hydroxyalkylation of 2-aminoimidazole with a suitably functionalized two-carbon aldehyde or pyruvic acid. To test this hypothesis, 2-aminoimidazole sulfate was heated at 95-100° C. with chloroacetaldehyde in concentrated hydrochloric acid for 24 hours. After basification to pH 12 and chromatography, parazoanthoxanthin A (1A) (41% yield) and pseudozoanthoxanthin A (2A) (7% yield) were obtained. Most importantly, moderate amounts of (1A) and (2A) were produced at room temperature after 7 days. Under acidic conditions, the proton serves as a natural protecting group for nitrogen as well as catalyst for hydroxyalkylation and subsequent dimerization. Similar results were seen with pyruvic acid and the more highly reduced two-carbon unit, acetaldehyde, but with less efficiency. Reactions involving pyruvic acid and acetaldehyde were carried out in 37% HCl between 95-100° C. for 24 hours. Acetaldehyde gave a 25% yield of parazoanthoxanthin A and pseudozoanthoxanthin A in a 3:1 ratio, respectively, whereas pyruvic acid produced a 15% yield of parazoanthoxanthin A and trace amounts of pseudozoanthoxanthin A. With these reactants, decarboxylation and/or final oxidation to the ten-electron azulene ring system is necessary (the oxidation is probably assisted by sulfuric acid derived from the commercial starting material, 2-aminoimidazole sulfate) and most likely accounts for the lower overall yields. At 23° C., the reaction between (AI) and acetaldehyde afforded products (12) (ref. 29); and (14) [Compound 5.2HCl, colorless solid, mp 240° C. (dec); 1H NMR (DMSO-D6, 300 MHz) δ ppm: 1.51 (d, 7.2 Hz, 3H), 3.97 (q, 7.2 Hz, 1H), 6.65 (s, 2H), 7.37 (s, 4H, exchanged with D2O), 11.85 (s, 2H, exchanged with D2O), 12.37 (s, 2H, exchanged with D2O); 13C NMR (free-base, DMSO-D6, 75.1 MHz) δ ppm: 20.0 (q), 30.4 (d), 111.0 (d), 135.8 (s), 148.9 (s); IR (nujol) υ cm−1: 3240, 3126, 1667; MS (CI, NH3) m/z 193 (MH+)] (10-40% yields); in addition to small amounts of zoanthoxanthins. Formation of (14) [Dimer (14), when heated at 95-100° C. with 1 eq. of acetaldehyde produced parazoanthoxanthin A], a precursor to parazoanthoxanthin A (1A), can be explained by dehydration of (12) to intermediate (B) followed by C-attack of the imidazole to the exocyclic double bond. Intermediate (14) could next undergo hydroxyalkylation with acetaldehyde followed by dehydration, cyclization, and oxidation to give (1A). A similar process in which initial addition to the endocyclic double bond of species (B) would account for the formation of pseudozoanthoxanthin A (2A), although no intermediates have been isolated. Whether the actual biosynthetic pathway proceeds via a sequential series of hydroxyalkylation-dimerization-hydroxyalkylation events involving 2-aminoimidazole or by direct dimerization of two C5N3 monomers (ref. 28, 29) remains to be determined. Our results in combination with the known metabolic conversion of arginine to (AI) (ref. 31) suggest that the key biosynthetic intermediate is not a direct product of arginine metabolism but evolves from hydroxyalkylation of arginine derived (AI). One additional consideration is formation of the methylated metabolites of zoanthoxanthins since they comprise the majority of pigments isolated. The parent compounds (1A) and (2A) could serve as potential precursors in a late methylation scheme, or contrastly, an early, predimeric methylation process would yield N-methylated 2-aminoimidazoles as biogenic forerunners.