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US 5,430,160 AGranted
Preparation of substituted isoserine esters using .beta.-lactams and metal or ammonium alkoxides
AssigneeFlorida State University
InventorRobert A. Holton
Life of this patent
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Abstract
A process for preparing N-acyl, N-sulfonyl and N-phosphoryl substituted isoserine esters in which a metal or an ammonium alkoxide is reacted with a .beta.-lactam.
Claims29
A process for the preparation of a substituted isoserine ester having the formula ##STR38## comprising reacting a .beta.-lactam with an alkoxide, the .beta.-lactam having the formula ##STR39## and the alkoxide having the formula ##STR40## wherein R.sub.1 is --OR.sub.6, --SR.sub.7, or --NR.sub.8 R.sub.9 ;
- R.sub.2 is hydrogen, alkyl, alkenyl, alkynyl, aryl, or heteroaryl;
- R.sub.3 and R.sub.4 are independently hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, or acyl, provided, however, that R.sub.3 and R.sub.4 are not both acyl;
- R.sub.5 is --COR.sub.10, --COOR.sub.10, --COSR.sub.10, --CONR.sub.8 R.sub.10, --SO.sub.2 R.sub.11, or --POR.sub.12 R.sub.13 ;
- R.sub.6 is hydrogen, alkyl, alkenyl. alkynyl, aryl, heteroaryl, or a hydroxy protecting group;
- R.sub.7 is alkyl, alkenyl, alkynyl, aryl, heteroaryl, or sulfhydryl protecting group;
- R.sub.8 is hydrogen, alkyl, alkenyl, alkynyl, aryl, or heteroaryl;
- R.sub.9 is an amino protecting group;
- R.sub.10 is alkyl, alkenyl, alkynyl, aryl, or heteroaryl;
- R.sub.11 is alkyl, alkenyl, alkynyl, aryl, heteroaryl, --OR.sub.10, or --NR.sub.8 R.sub.14 ;
- R.sub.12 and R.sub.13 are independently alkyl, alkenyl, alkynyl, aryl, heteroaryl, --OR.sub.10, or --NR.sub.8 R.sub.14 ;
- R.sub.14 is hydrogen, alkyl, alkenyl, alkynyl, aryl, or heteroaryl;
- M is an ammonium containing substituent;
- E.sub.1 and E.sub.2 and the carbon to which they are attached comprise a carbocyclic or a heterocyclic skeleton having about 6-20 ring atoms, the hereto atoms of the heterocyclic skeleton being oxygen;
- and
- E.sub.3 is hydrogen or a hydrocarbon.
12 more elements
A process for the preparation of a taxane comprising:
- reacting an alkoxide having the formula MOCE.sub.1 E.sub.2 E.sub.3 with a .beta.-lactam to forman intermediate and converting the intermediate to the taxane, wherein the .beta.-lactam has the formula:
- ##STR44## M is an ammonium containing substituent;
- one of E.sub.1, E.sub.2 and E.sub.3 is hydrogen or a hydrocarbon and the other two of E.sub.1, E.sub.2 and E.sub.3 together with the carbon to which they are attached comprise a taxane,
- R.sub.1 is --OR.sub.6, --SR.sub.7, or--NR.sub.8 R.sub.9 ;
- R.sub.2 is hydrogen, alkyl, alkenyl, alkynyl, aryl, or heteroaryl;
- R.sub.3 and R.sub.4 are independently hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, or acyl, provided, however, that R.sub.3 and R.sub.4 are not both acyl;
- R.sub.5 is --COR.sub.10, --COOR.sub.10, --CONR.sub.8 R.sub.10, --COSR.sub.10, --SO.sub.2 R.sub.11, or --POR.sub.12 R.sub.13 ;
- R.sub.6 is hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, or hydroxy protecting group,
- R.sub.7 is alkyl, alkenyl, alkynyl, aryl, heteroaryl, or sulfhydryl protecting group,
- R.sub.8 is hydrogen, alkyl, alkenyl, alkynyl, aryl, or heteroaryl;
- R.sub.9 is an amino protecting group;
- R.sub.10 is alkyl, alkenyl, alkynyl, aryl, or heteroaryl,
- R.sub.11 is alkyl, alkenyl, alkynyl, aryl, heteroaryl, --OR.sub.10, or --NR.sub.8 R.sub.14,
- R.sub.12 and R.sub.13 are independently alkyl, alkenyl, alkynyl, aryl, heteroaryl, --OR.sub.10, or --NR.sub.8 R.sub.14 ;
- and
- R.sub.14 is hydrogen, alkyl, alkenyl, alkynyl, aryl, or heteroaryl.
13 more elements
A process for the preparation of taxol comprising reacting an alkoxide with a .beta.-lactam wherein,
- the alkoxide has the formula ##STR48## the .beta.-lactam has the formula:
- ##STR49## Z is --OCOCH.sub.3 or --OT.sub.2, T.sub.1 is a hydroxy protecting group,
- T.sub.2 is a hydroxy protecting group,
- Ph is phenyl,
- Ac is acetyl,
- M is an ammonium containing substituent,
- R.sub.1 is --OR.sub.6,
- R.sub.2 is hydrogen,
- R.sub.3 is phenyl,
- R.sub.4 is hydrogen,
- R.sub.5 is --COR.sub.10,
- R.sub.6 is a hydroxy protecting group, and R.sub.10 is phenyl.
9 more elements
Dependencies are inferred from the claim text.