Base catalyzed racemization of amino acid derivatives

Amino acid thioesters used as substrates for a chemo-enzymatic dynamic kinetic resolution (DKR) must be designed with a high enough acidity to be rapidly racemized in the presence of a suitable base. Kinetic data obtained from experimental proton exchange rates are correlated with thermodynamic data for the proton abstraction based on the density functional theory (DFT) calculations. The good correlation obtained allows to evaluate the contribution of different functional groups to the carbon acidity and to define bases able to perform the required racemization.

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(S)-N-Boc-phenylglycine-thioethyl esterC15H21NO3S[α]D25=+151.15 (c 1.1, CHCl3)Source of chirality: esterification of the N-Boc-amino acidAbsolute configuration: (S)

(S)-N-Boc-phenylglycine-thioethyl esterC15H21NO3S[α]D20=+73.6 (c 1.0, isopropanol)Source of chirality: esterification of the N-Boc-amino acidAbsolute configuration: (S)

(S)-S-Ethyl 2-(tert-butoxycarbonylamino)-2-(thiophen-2-yl)ethanethioateC13H19NO3S2[α]D20=+28.65 (c 1.0, isopropanol)Source of chirality: esterification of the N-Boc-amino acidAbsolute configuration: (S)

(S)-N-Boc-phenylalanine-thioethyl esterC16H23NO3S[α]D20=+24.4 (c 1.0, isopropanol)Source of chirality: esterification of the N-Boc-amino acidAbsolute configuration: (S)

(S)-N-Boc-phenylalanine-thiobenzyl esterC21H25NO3S[α]D20=+22.0 (c 1.0, isopropanol)Source of chirality: esterification of the N-Boc-amino acidAbsolute configuration: (S)

(S)-N-Boc-homophenylalanine-thioethyl esterC17H25NO3S[α]D20=+16.55 (c 1.0, isopropanol)Source of chirality: esterification of the N-Boc-amino acidAbsolute configuration: (S)

(S)-N-Boc-homophenylalanine-thiobenzyl esterC22H27NO3S[α]D20=+13.4 (c 1.0, isopropanol)Source of chirality: esterification of the N-Boc-amino acidAbsolute configuration: (S)

(S)-N-Boc-norleucine-thioethyl esterC13H25NO3S[α]D20=+20.3 (c 1.0, isopropanol)Source of chirality: esterification of the N-Boc-amino acidAbsolute configuration: (S)

(S)-N-Boc-norleucine-thiobenzyl esterC18H27NO3S[α]D20=+21.6 (c 1.0, isopropanol)Source of chirality: esterification of the N-Boc-amino acidAbsolute configuration: (S)