Presentation Title

Diastereoselective Synthesis of Unnatural Amino Acids via Auxiliary-Directed Enolate Alkylation

Faculty Mentor

Jeffrey S. Cannon

Start Date

17-11-2018 12:30 PM

End Date

17-11-2018 2:30 PM

Location

CREVELING 99

Session

POSTER 2

Type of Presentation

Poster

Subject Area

physical_mathematical_sciences

Abstract

We aim to diastereoselectively synthesize unnatural amino acids (UAAs) by incorporating chiral auxiliaries into substrate compounds prior to performing enolate alkylations. Diastereoselective synthesis of UAAs is worthwhile because the difference in the stereochemistry of a biological molecule dictates its biochemical significance, and selectively synthesizing a specific geometric configuration may prove useful in further studies in biology as well as in pharmaceutical pursuits. To achieve this, our project uses the commercially available and easily synthesized tert-butanesulfinamide auxiliary developed by Ellman. The hypothesis is that the attachment of this chiral auxiliary, followed by an enolate alkylation at the alpha-carbon, followed by the subsequent removal of said auxiliary theoretically affords a diastereomerically enriched product. Previous studies conducted on the scope of stereoselective sulfinamidoester alkylation has shown promising results both in terms of yield and diastereomeric ratios. The immediate next step taken towards diastereoselective synthesis of unnatural amino acids was to investigate the ability of the chiral substrate to control multiple stereocenters. Initial attempts at the aldol reaction and the Ireland-Claisen rearrangements have been challenging, with results showing some promise for future success in optimization and improvements in diastereomeric ratios. We expect that the optimized conditions for the alkylation will serve as the key to unlock the potential of the diastereoselective synthesis for a greater scope of alpha-substitution.

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Nov 17th, 12:30 PM Nov 17th, 2:30 PM

Diastereoselective Synthesis of Unnatural Amino Acids via Auxiliary-Directed Enolate Alkylation

CREVELING 99

We aim to diastereoselectively synthesize unnatural amino acids (UAAs) by incorporating chiral auxiliaries into substrate compounds prior to performing enolate alkylations. Diastereoselective synthesis of UAAs is worthwhile because the difference in the stereochemistry of a biological molecule dictates its biochemical significance, and selectively synthesizing a specific geometric configuration may prove useful in further studies in biology as well as in pharmaceutical pursuits. To achieve this, our project uses the commercially available and easily synthesized tert-butanesulfinamide auxiliary developed by Ellman. The hypothesis is that the attachment of this chiral auxiliary, followed by an enolate alkylation at the alpha-carbon, followed by the subsequent removal of said auxiliary theoretically affords a diastereomerically enriched product. Previous studies conducted on the scope of stereoselective sulfinamidoester alkylation has shown promising results both in terms of yield and diastereomeric ratios. The immediate next step taken towards diastereoselective synthesis of unnatural amino acids was to investigate the ability of the chiral substrate to control multiple stereocenters. Initial attempts at the aldol reaction and the Ireland-Claisen rearrangements have been challenging, with results showing some promise for future success in optimization and improvements in diastereomeric ratios. We expect that the optimized conditions for the alkylation will serve as the key to unlock the potential of the diastereoselective synthesis for a greater scope of alpha-substitution.