Synthesis and biological evaluation of (S)-4-aminoquinazoline alcohols

A simple synthetic method for the preparation of enantiomerically pure (S)-4-aminoquinazoline alcohols from (S)-quinazolinone alcohols by key steps including chlorination, nucleophilic ipso substitution, and deacetylation is presented. Mutagenic and antimutagenic properties of the (S)-4-aminoquinazoline alcohols were investigated by using Salmonella typhimurium TA1535, and Escherichia coli WP2uvrA tester strains at 0.01, 0.1, and 1 μg/plate concentrations. (S)-4-aminoquinazoline alcohols were found to be genotoxically safe at the tested concentrations. Among the tested (S)-4-aminoquinazoline alcohols, the best antimutagenic activity was obtained with a methyl derivative at 0.1 μg/plate dose.

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(S)-1-(4-Oxo-3,4-dihydroquinazolin-2-yl)ethyl acetateC12H12N2O3Ee: 99%[α]D20=-70.9 (c 1, EtOH)Source of chirality: l-lactic acidAbsolute configuration: (S)

(S)-2-Methyl-1-(4-oxo-3,4-dihydroquinazolin-2-yl)propyl acetateC14H16N2O3Ee: 99%[α]D20=-64.2 (c 1, EtOH)Source of chirality: l-valineAbsolute configuration: (S)

(S)-2,2-Dimethyl-1-(4-oxo-3,4-dihydroquinazolin-2-yl)propyl acetateC15H18N2O3Ee: 99%[α]D20=-19.2 (c 0.52, EtOH)Source of chirality: l-tert-leucineAbsolute configuration: (S)

(S)-(4-Oxo-3,4-dihydroquinazolin-2-yl)(phenyl)methyl acetateC17H14N2O3Ee: 99%[α]D20=+49.0 (c 1, EtOH)Source of chirality: l-mandelic acidAbsolute configuration: (S)

(S)-1-(4-Oxo-3,4-dihydroquinazolin-2-yl)-2-phenylethyl acetateC18H16N2O3Ee: 99%[α]D20=-16.5 (c 1, EtOH)Source of chirality: l-phenylalanineAbsolute configuration: (S)

(S)-1-(4-Chloroquinazolin-2-yl)ethyl acetateC12H11ClN2O2[α]D20=-98.7 (c 1, CH2Cl2)Source of chirality: l-lactic acidAbsolute configuration: (S)

(S)-1-(4-Chloroquinazolin-2-yl)-2-methylpropyl acetateC14H15ClN2O2[α]D20=-86.7 (c 1, CH2Cl2)Source of chirality: l-valineAbsolute configuration: (S)

(S)-1-(4-Chloroquinazolin-2-yl)-2,2-dimethylpropyl acetateC15H17ClN2O2Ee: 99%[α]D20=-17.0 (c 1, CH2Cl2)Source of chirality: l-tert-leucineAbsolute configuration: (S)

(S)-(4-Chloroquinazolin-2-yl)(phenyl)methyl acetateC17H13ClN2O2Ee: 99%[α]D20=+52.0 (c 1, CH2Cl2)Source of chirality: l-mandelic acidAbsolute configuration: (S)

(S)-1-(4-Chloroquinazolin-2-yl)-2-phenylethyl acetateC18H15ClN2O2Ee: 99%[α]D20=-35.5 (c 1, CH2Cl2)Source of chirality: l-phenylalanineAbsolute configuration: (S)

(S)-1-(4-Aminoquinazolin-2-yl)ethanolC10H11N3OEe: 99%[α]D20=-66.5 (c 1, EtOH)Source of chirality: l-lactic acidAbsolute configuration: (S)

(S)-1-(4-Aminoquinazolin-2-yl)-2-methylpropan-1-olC12H15N3OEe: 99%[α]D20=-56.6 (c 1, EtOH)Source of chirality: l-valineAbsolute configuration: (S)

(S)-1-(4-Aminoquinazolin-2-yl)-2,2-dimethylpropan-1-olC13H17N3OEe: 99%[α]D20=-57.0 (c 1, EtOH)Source of chirality: l-tert-leucineAbsolute configuration: (S)

(S)-(4-Aminoquinazolin-2-yl)(phenyl)methanolC15H13N3OEe: 99%[α]D20=+30.4 (c 1, EtOH)Source of chirality: l-mandelic acidAbsolute configuration: (S)

(S)-1-(4-Aminoquinazolin-2-yl)-2-phenylethanolC16H15N3OEe: 99%[α]D20=-40.5 (c 1, EtOH)Source of chirality: l-phenylalanineAbsolute configuration: (S)