Amino Acids in Synthesis

We found that simple amino acids may serve as very effective chiral inducing agents in diastereoselective synthesis of heterocyclic systems. We used mild Pictet-Spengler-type condensation to the synthesis of several tetrahydro-β-carboline and tetrahydroisoquinoline derivatives. L-Amino acids were promoters of 1,4-chirality transfer with up to 100% de. The stereochemistry of the final diketopiperazines strongly depended on the structure of the L-amino acids used: acyclic amino acids gave predominantly the (R)-configuration at the newly created stereogenic centre, whereas L-proline afforded the opposite configuration, as established by X-ray crystallography.

fig 1

We synthesized the Markovnikov-type enol esters selectively from N-protected amino acids by ruthenium-mediated coupling with the appropriate acetylenes.

fig 2

The presence of a carbon–carbon double bond in enol esters allows their application in many different types of reactions in sustainable organic chemistry.

The introduction of the chiral carboxylic acid moiety allows diastereofacial functionalization of the double bond which may find applications in procedures aimed at preparing enantiomerically enriched products.

 

Zawadzka A., Leniewski A., Maurin J.K., Wojtasiewicz K., Czarnocki Z., “Diastereoselective Synthesis of 1-Benzyltetrahydroisoquinoline Derivatives from Amino Acids via 1,4 Chirality Transfer. Part I”  Organic Letters, 3, 997-999 (2001)

Zawadzka A., Leniewski A., Maurin J.K., Wojtasiewicz K., Siwicka A., Błachut D., Czarnocki Z., “Diastereoselective Synthesis of 1-Benzyltetrahydroisoquinoline Derivatives from Amino Acids by 1,4 Chirality Transfer”, Eur. J. Org. Chem., 2443-2553 (2003)

Zawadzka A., Leniewski A., Maurin J.K., Wojtasiewicz K., Siwicka A., Czarnocki Z., “Synthesis and Crystal Structure of Hydrogenated Pyrazino[2,1-a]isoquinoline Derivatives”, Pol. J. Chem., 77, 565-576 (2003)

Siwicka A., Wojtasiewicz K., Zawadzka A., Maurin J.K., Czarnocki Z., “The structure of some trans-diketopiperazine derivatives of isoquinoline and β-carboline”, Tetrahedron: Asymmetry, 16, 2071-2073 (2005)

Siwicka A., Wojtasiewicz K., Rosiek B., Leniewski A., Maurin J.K., Czarnocki Z., “Diastereodivergent synthesis of 2,5-diketopiperazine derivatives of β-carboline and isoquinoline from L-amino acids”, Tetrahedron: Asymmetry, 16, 975-993 (2005)

Kalinowska I.M., Szawkało J., Krawczyk K.K., Maurin J.K., Czarnocki Z.

“Diastereoselective transformations of enol esters derived from acetylenes and chiral carboxylic acid”, Synthesis, 11, 1809-1813 (2011)

Comments are closed

Do NOT follow this link or you will be banned from the site!