Repository logo

Asymmetric syntheses of cyclopropane-containing amino acids




Fegley, Glenn Jeffery, author
Williams, Robert M., advisor

Journal Title

Journal ISSN

Volume Title


Chiral, non-racemic (D)-erythro-4-(tert-butoxycarbonyl)-3-(dimethoxyphosphoryl)- 5,6-diphenyl-2,3,5,6-tetrahydro-4H-1,4-oxazin-2-one was efficiently condensed with various alkyl and aryl aldehydes via the Emmons-Horner-Wadsworth procedure to provide the corresponding (E)-α,β-dehydrolactones. These compounds were smoothly cyclopropanated by racemic sodium [(diethylamino)phenyl]oxosulfonium methylide to furnish in high chemical and optical yields the desired cyclopropyllactones. Interestingly, the ylide consistently delivered the methylene unit almost exclusively syn to the C-5 and C-6 phenyl rings of the α,β-dehydrolactones. Removal of the chiral auxiliary was accomplished by dissolving-metal reduction using lithium metal and liquid ammonia to afford the corresponding t-BOC-protected 2-alkyl-1-aminocyclopropane-1-carboxylic acids in good yield. Sequential treatment of these protected amino acids with anhydrous methanolic HCl (or aqueous HCl) and propylene oxide provided the corresponding free amino acids in high chemical and optical yields. In this fashion the asymmetric syntheses of (1S)-[2,2-2H2]ACC, (1S,2S)-MeACC (norcoronamic acid), (1S,2S)-EtACC (coronamic acid), (1S,2S)-PrACC, and three diastereomers of cyclopropyldiaminopimelic acid (cyclopropylDAP) were achieved in 83-99% de. Deblocking of a phenyl-substituted cyclopropyllactone was accomplished via a stepwise sequence involving the lead tetraacetate cleavage of the chiral auxiliary as the key step. This protocol furnished (1S,2R)-2-phenyl-1-aminocyclopropane-1-carboxylic acid in greater than 95% de, and revealed a potential route to other aromatic-substituted cyclopropane amino acids. Finally, several (E)- α,β-dehydrolactones were treated with the azomethine ylide of N-benzyl-N-(methoxymethyl)-N-[(tlimethylsilyl)methyl]amine to furnish the corresponding spiropyrrolidine lactones in moderate to excellent yields and in high diastereomeric excesses. Deprotection of one spiropyrrolidine adduct by palladium-catalyzed hydrogenolysis resulted in the synthesis of enantiomerically pure (S)-(-)-cucurbitine.


Rights Access


Organic compounds -- Synthesis
Amino acids


Associated Publications