Amino acids yields from neutral atmospheres

We have reinvestigated abiotic synthesis from model neutral atmospheres (CO2/N2/H2O) and found that amino acid yields are much higher than previously reported. As discussed here, our results suggest that the previously reported low yields were likely the result of both the experimental conditions and the analytical procedures. 

Table 1. Yields of Amino Acids and other Small Molecules from Neutral Atmospheres. 

Dimethyl-2-oxazoline is commercially available from Columbia Organic Chemicals, 912 Drake Street, Columbia, South Carolina, or may be prepared as follows. In a 250-ml., three-necked flask is placed 89.14 g. (1.0 mole) of 2-amino-2-methyl-l-propanol, and the flask is cooled in an ice bath. The amine is carefully neutralized with 52.3 g. (1.0 mole) of 90.6% formic acid over a 1-hour period. A magnetic stirring bar is added, the flask is fitted with a short path distillation head, and the reaction mixture is placed in a silicon oil bath which is rapidly heated to 220-250°. The azeotropic mixture of water and oxazoline distills over a period of 2-4 hours and is collected in an ioe-cooled flask containing ether. The aqueous layer is separated, saturated with sodium chloride, and extracted with three 50-ml. portions of ether. The combined ethereal extracts are dried over potassium carbonate, filtered to remove the drying agent, and the ether is removed at 35-40° at atmospheric pressure. The 4,4-dimethyl-2-oxazoline is collected as the temperature rises above 85°. The yield is 56.7-62.7 g. (57—63%) of a colorless mobile liquid, b.p. 99-100° (758 mm. Hg). 

To a suspension of 77.7 mg 4-amino-l-(3,4-dihydroxy-5-hydroxymethyltetra-hydrofuran-2-yl)-lH-pyrimidin-2-one 3-oxide (cytidine -oxide, 0.30 mmol) and 12.6 mg 95% pure lithium hydride (1.5 mmol) in 5 mL dry methanol was added 40 /xL 98% pure benzyl bromide (0.33 mmol) the mixture was stirred at 37°C for 1 day under an argon atmosphere. TLC analysis of the reaction mixtures with chloroform/methanol/acetic acid (16 6 3) and chloroform/methanol (10 1) as the developing solvents showed complete consumption of the starting material for almost quantitative conversion to a less polar compound. After being neutralized with 1 N HCl solution and subsequent removal of the solvent under reduced pressure, the resulting residue was subjected to a short silica gel column by eluting with chloroform/methanol (20 1) to isolate 99.5 mg l-(3,4-dihydroxy-5-hydroxymethyltetrahydrofuran-2-yl)-17/-pyrimidin-2,4-dione 4- 0-benzyl oxime (uridine 4-0-benzyloxime) as a colorless amorphous powder, in a yield of 95%, m.p. 123-125°C (from methanol). 

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