3-N‘Oxalyl

Olney, J.W., Misra, C.H. and Rhee, V. (1976b). Brain and retinal damage from the lathyrus excitotoxin, /3-N-oxalyl-L-ajS-diaminopropionic acid (ODAP). Nature 264 659-661. 

Most of the early syntheses of psilocin and psilocybin employ the O-benzyl ether as a protecting group. This provides more stability to the chemical intermediates, but also requires the additional step of reductive debenzylation. The flow chart of this process is conversion of 4-hydroxyindole to 4-benzyloxyindole via the sodium salt, with benzyl chloride the conversion of this with oxalyl chloride to 4-benzyloxyindole-3-glyoxylchloride the conversion of this to 4-benzyloxy-3-(N,N-dimethyl-glyoxamide with anhydrous dimethylamine the conversion of this to... 

Scheme22 a [81,82] b 1M vinylmagnesium bromide, THE, -40°C, 30 C then saturated NaHCOs C oxalyl chloride, DMSO, EtsN, - 78 °C, CH2CI2 then saturated NaHCOs, 91% d 3 equiv. (S)-BINAL, THE, - 78 °C, 1 h, 89% e EtsN, CH2CI2, DMAP, AC2O, rt, 2 h, 98% f sat NaHCOs, THE, Et20, iodine, rt, 36h, 90% g silver benzoate, toluene, 12h, 92% h L1A1H4, THE, 0 °C, 30 min, 94% i H2, Pd/C, EtOAc, rt, 6h, then MeOH, Dowex 50W-X8, then added 3 N NH4OH, 89%...

N -Oxalyl-L-2,3-diaminopropionic acid (57) is derived from 2,3-diaminopropionic acid (69), which, in turn, is derived from asparagine (64) (Fig. 13.13), The oxalyl derivative (57) is a potent neurotoxin found in Lathyrus sativus and certain other legumes. The corresponding. /V -methyl derivative occurs in certain cycads such as Cycas drdnalis (Rosenthal, 1991). 

Consumption of seeds of the genus Lathyrus (Fabaceae) by man and his domestic animals produces a syndrome called lathyrism. Different amino acids produce the two forms of this malady neurolathyrism and osteolathyrism. 3-Aminopropionitrile 0-aminopropionitrile) (59) is the active osteolathyritic factor in Lathyrus species. Several factors are responsible for neurolathyrism. 3-Cyanoalanine (58), its 4-glutamyl derivative, 2,4-diaminobutyric acid (56), and the N-oxalyl derivative of 2,3-diaminopropionic (a,3-diamino-propionic) acid (57) are all known to be involved. These compounds are found primarily in plants of the genus iMth-yrus. 3-Cyanoalanine (58) and its 4-glutamyl derivative are also common in Vida species. Several related series of compounds are found in other members of the Fabaceae. 

Vilsmeier-Haack formylation of 2-(4-methyl-l-piperazinyl)-4//-pyrido-[l,2-n]pyrimidin-4-one with a mixture of POCI3 and DMF at 95°C gave a 3-formyl derivative (93FES1225) while ethyl 4-oxo-6,7,8, 9-tetrahydro-4//-pyrido[l,2-n]pyrimidine-2-acetate at 50 °C yielded a 9-dimethylaminomethylene-3-formyl derivative (01MI4). 3-Formyl-2-hydroxy-8-[2-(4-isopropyl-l,3-thiazol-2-yl)-l-ethenyl]-4//-pyrido[l,2-n]pyri-midin-4-one was obtained from the 3-unsubstituted derivative with oxalyl chloride-DMF reagent in CH2CI2 at room temperature for 3h (OlMIPl). 

To a stirred suspension of p-(p-methoxvbenzyloxy)-phenylmalonic acid (125 mg) in methylene chloride (3 ml) are added triethylamine (55 All) and oxalyl chloride (26 AH) at -15°C, and the suspension is stirred for 40 minutes at 0°C. The mixture Is added to a solution of diphenylmethyl 7 -amino-7a-methoxy-3-(1 -methyltetrazol-5-yl)thiomethyl-1 -oxadethia-3-cephem-4methylene chloride (3 ml) and pyridine (63 AH), and the mixture is stirred for 30 minutes at 0°C. The reaction mixture is diluted with ethyl acetate, washed with aqueous 2 N-hydrochloric acid and water, dried over sodium sulfate, and concentrated to give crude product (212 mg), which Is chromatographed on silica gel (20 g) and... 

Oxa-7,7-dichloronorcarane, 41, 76 Oxalyl chloride, condensation, with N,N-diethylaniline, 41, 3 with N,N-dimethylaniline, 41, 1 with N,N-di- -propylaniline, 41, 3... 

In 2001, Knaack and co-workers56 reported an application of the INADEQUATE experiment in the course of synthesizing and characterizing a biologically active 2-[l-(4-chlorobenzyl)-lH-indol-3-yl]-2-oxo-N-pyri-din-4-yl acetamide (6). Treatment of l-(4-chlorobenzyl)-lH-indole with oxalyl chloride afforded the corresponding oxoacetyl chloride that was finally subjected to aminolysis with 4-aminopyridine to afford the final product of the reaction scheme, 6. Although the NMR data supported the N-benzyl structure, a 1,1-ADEQUATE spectrum was acquired to provide additional confirmation of the structure of 6. 

N,N-Diethylaniline, condensation with oxalyl chloride, 41, 3 Diethyl bis(hydsoxymethyl)malo-nate, 40, 27... 

D. 1 -[N-Benzyloxycarbonyl-(IS)-1 -amino-2-oxoethyl]-4-methyl-2,6,7-trioxabi-cyclo[2.2.2]octane, [Cbz-L-Ser(ald) OBO ester, (4)7 Cbz-Ser OBO ester 3 (9.10 g, 28.0 mmol) (Note 21) is dissolved in dry CH2CI2 (80 mL) (Note 14) under Ar and cooled to -78°C in a 100-mL, round-bottomed flask labeled flask 1. Oxalyl chloride (3.9 mL, 45 mmol, 1.61 equiv) (Note 22) is added to dry CH2CI2 (120 mL) (Note 14) in a separate 250-mL, round-bottomed flask (flask 2) under Ar, and cooled to -78°C. Dry dimethyl sulfoxide (DMSO, 7.0 mL, 90 mmol, 3.21 equiv) (Note 23) is added to the oxalyl chloride solution (flask 2) and the mixture is stirred under Ar (magnetic stir bar) at -78°C for 15 min. The alcohol solution 3 (in flask 1) is transferred slowly by cannula to flask 2 over a period of 45 min and then rinsed with dry CH2CI2 (50 mL) (Note 14). The resulting cloudy white... 

Even an oligopeptide has been attached to (Table 4.3, compound 130) [111]. This was achieved by a coupling reaction of the carboxylic group in the side chain of the cyclopropane ring as well. First, the tert-butylcarboxylate 129 was synthesized by the reaction of the corresponding diazomethylbenzoate with Cgg. After hydrolysis with trifluoromethanesulfonic acid, the acyl chloride was generated by treatment with oxalyl chloride. Finally, in a one-step procedure the fullerene peptide 130 was obtained by the reaction with the N-deprotected pentapeptide H-(L-Ala-Aib)2-L-Ala-OMe. 

The action of phosphorus halides on pyrrolinones and related compounds offers an alternative route to chloropyrroles. Yields of around 60% of 2,5-dichloropyrroles were obtained in this way from N-substituted succinimides (82ZC126). Vilsmeier reaction of N-alkylsuccinimidals formed chlorinated pyrrole aldehydes in modest yields (90CJC791), and there are other examples [66YZ158 81H(15)547]. A useful synthesis of chloropyrrole-2-carboxylates employed the action of phosphorus pentachloride on pyrrolidin-2-one-5-carboxylates (40) (87CB45) (Scheme 15), and in a Pummerer-type reaction pyrrol-3-yl sulfoxides were transformed by thionyl chloride into chloropyrroles. Yields were increased to >80% by the use of oxalyl chloride (88JOC2634) (Scheme 15). 

A. N,N-Dimethylchloromethylenammonium chloride. A 500-mL, three-necked, round-bottomed flask is equipped with a magnetic stirring bar, thermometer (Note 1), and a three way stopcock fitted with a drying tube containing anhydrous calcium chloride and a rubber septum. The flask is charged with 50 mL of dichloromethane (Note 2) and 3.07 g (0.042 mol) of N,N-dimethylformamide (Note 3) added throu i the septum from a syringe, and cooled in an ice bath. To the cooled mixture is slowly added 5.23 mL (0.06 mol) of oxalyl chloride (Note 4) by means of a syringe. The addition 1s accompanied by gas evolution and formation of a white precipitate. The reaction mixture is stirred for an... 

Cooling below —10° should be avoided because the reaction stops at that temperature and large amounts of oxalyl chloride accumulate in the flask. If this mixture is then allowed to come to room temperature, a vigorous reaction that may get out of control will take place. It is probable that, at reaction temperatures about 10°, the yield of 4,4,-bis(dimethylamino)benzil is less and some Crystal Violet is formed as an impurity, for it has been reported that aluminum chloride effects the conversion of N,N-dimetbylaniline and oxalyl chloride to Crystal Violet in 92-95% yield when the reaction is allowed to proceed without cooling.2... 

SYNTHESIS (from indole) To a well stirred solution of 10 g of indole in 100 mL MTBE, cooled to 0 °C with an ice bath, there was added 8.6 g oxalyl chloride. The reaction mixture was stirred for 0.5 hr, and the solids removed by filtration and washed twice with 50 mL MTBE. This acid chloride was added to 20 mL anhydrous diisopropylamine. There was then added an excess of 2N HCI, the mixture cooled, and the resulting solids removed by filtration. These were recrystallized from MeOH to give, after air drying, 11.4 g (49%) indol-3-yl N,N-diisopropylglyoxylamide with a mp of 200-202 °C. 

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