Back to results
US 5,294,737 AGranted
Process for the production of chiral hydroxy-.beta.-lactams and hydroxyamino acids derived therefrom
AssigneeThe Research Foundation of State University of New York
InventorIwao Ojima
Life of this patent
Estimating the term…
Abstract
The reaction between a hydroxyacetic acid derivative bearing an oxygen protecting group and a chiral auxiliary group and an imine produces chiral .beta.-lactams. Hydrolysis of the chiral .beta.-lactams produces chiral amino acid analogs.
Claims15
A process for the production of a hydroxyamino acid with high enantiomeric purity from a chiral .beta.-lactam of the formula:
- ##STR29## wherein R.sup.1 is as defined below in an imine;
- R.sup.2 is selected from the group consisting of hydrogen, and the groups for R.sup.7 defined below in the imine;
- R.sup.3 is hydrogen or an oxygen protecting group R.sup.4 ;
- comprising reacting an O-protected hydroxyacetic acid derivative of the formula
- R.sup.4 OCH.sub.2 C(O)Xc
- wherein
- R.sup.4 is an oxygen protecting group;
- Xc is a chiral auxiliary;
- with a base of the formula
- MNR.sup.5 R.sup.6
- wherein
- M is an alkali metal;
- R.sup.5 and R.sup.6 are independently selected from the group consisting of C.sub.1 -C.sub.10 branched or straight chain alkyl, C.sub.3 -C.sub.10 cycloalkyl and trialkylsilyl of C.sub.3 -C.sub.18 ;
- followed by cyclocondensing with an imine having the formula
- R.sup.1 CH.dbd.NR.sup.7
- wherein
- R.sup.1 is selected from a group consisting of C.sub.1 -C.sub.20 branched or straight chain alkyl, C.sub.3 -C.sub.10 cycloalkyl, C.sub.2 -C.sub.20 alkenyl, C.sub.2 -C.sub.20 alkynyl, C.sub.6 -C.sub.20 substituted aryl, C.sub.3 -C.sub.20 heteroaromatic and C.sub.3 -C.sub.20 substituted heteroaromatic;
- R.sup.7 is selected from the group consisting of C.sub.1 -C.sub.20 branched or straight chain alkyl, C.sub.3 -C.sub.20 cycloalkyl, C.sub.2 -C.sub.20 alkenyl, C.sub.2 -C.sub.20 alkynyl, C.sub.6 -C.sub.20 aryl, C.sub.6 -C.sub.20 substituted aryl, C.sub.3 -C.sub.20 heteroaromatic, C.sub.3 -C.sub.20 substituted heteroaromatic and trisubstituted silyl of C.sub.3 -C.sub.20 and hydrolyzing the .beta.-lactam to produce the corresponding hydroxyamino acid.
15 more elements
The process of claim 2 wherein the oxygen protecting group R.sup.4 has the formula 2:
- R.sup.8 R.sup.9 R.sup.10 Y-- 2
- wherein
- R.sup.8, R.sup.9 AND R.sup.10 are independently selected from the group consisting of C.sub.1 -C.sub.10 branched or straight chain alkyl, C.sub.1 -C.sub.10 alkoxy, C.sub.3 -C.sub.20 cycloalkyl, C.sub.2 -C.sub.20 alkenyl, C.sub.2 -C.sub.10 alkynyl, C.sub.6 -C.sub.15 aryl, C.sub.6 -C.sub.15 substituted aryl, C.sub.3 -C.sub.15 aryloxy, C.sub.3 -C.sub.20 substituted heteroaromatic, trialkylsilyl of C.sub.3 -C.sub.18 and trialkysiloxy of C.sub.3 -C.sub.18 and trialkylsiloxy of C.sub.3 -C.sub.18 ;
- Y is selected from the group consisting of carbon, silicon, germanium, and tin;
- or formula 3:
- R.sup.11 R.sup.12 Z-- 3
- wherein
- R.sup.11 and R.sup.12 are independently selected from the group consisting of C.sub.1 -C.sub.10 branched or straight chain alkoxy, C.sub.3 -C.sub.10 cycloalkyloxy, C.sub.6 -C.sub.15 aryloxy, C.sub.6 -C.sub.15 substituted aryloxy, C.sub.3 -C.sub.20 heteroaromatic, C.sub.3 -C.sub.20 substituted heteroaromatic, trialkylsilyl of C.sub.3 -C.sub.18 and trialkylsiloxy of C.sub.3 -C.sub.18 ;
- and
- Z is boron or aluminum.
7 more elements
Dependencies are inferred from the claim text.