EP 0641347 A1 19950308 - METHOD FOR MAKING A PROLINEBORONATE ESTER.
Title (en)
METHOD FOR MAKING A PROLINEBORONATE ESTER.
Title (de)
Verfahren zur Herstellung von Prolineboronat ester.
Title (fr)
PROCEDE DE PRODUCTION D'UN ESTER DE PROLINEBORONATE.
Publication
Application
Priority
- US 9209845 W 19921119
- US 79614891 A 19911122
- US 93619892 A 19920826
Abstract (en)
[origin: WO9310127A1] A method for the preparation of esters of prolineboronic acid is described. An N-protected pyrrole (I) is lithiated at the 2-position. The lithiated species (II) is reacted with trialkylborate, to yield a protected pyrrole-2-boronic acid (III). This is reduced to form a protected prolineboronic acid (IV), which, in turn, is reacted with a diol to yield an ester (VI). With the boronic acid moiety protected by the ester group, the protecting group on the nitrogen is removed, yielding the desired prolineboronic acid ester (VII). In an alternative synthesis, a protected pyrrolidine (VIII) is lithiated at the 2-position to yield a protected 2-lithio-pyrrolidine (IX). This is reacted with trialkylborate to yield the intermediate IV. The prolineboronic acid esters so produced have a chiral center to the boron atom. Also disclosed are methods for resolving enantiomers. The final products can be coupled to activated carboxylic acids, to yield peptides having a prolineboronic acid ester, instead of an amino acid, at the C-terminus. These boronic acid peptide analogs are useful for inhibiting biologically important proteases. Several methods for removing pinanediol from pinanediol boronate esters are also disclosed.
IPC 1-7
IPC 8 full level
C07B 61/00 (2006.01); C07F 5/02 (2006.01)
IPC 8 main group level
C07D 207/00 (2006.01); C07D 403/00 (2006.01)
CPC (source: EP)
C07F 5/025 (2013.01); Y02P 20/55 (2015.11)
Citation (search report)
See references of WO 9310127A1
Designated contracting state (EPC)
AT BE CH DE DK ES FR GB GR IE IT LI LU MC NL SE
DOCDB simple family (publication)
WO 9310127 A1 19930527; AU 3136893 A 19930615; AU 661362 B2 19950720; CA 2123128 A1 19930527; CN 1073946 A 19930707; CZ 124494 A3 19950712; EP 0641347 A1 19950308; FI 942345 A0 19940520; FI 942345 A 19940520; HU 9401350 D0 19940829; HU T67937 A 19950529; IL 103817 A0 19930404; JP H07501078 A 19950202; MX 9206628 A 19930501; NO 941905 D0 19940520; NO 941905 L 19940714; NZ 245207 A 19940726; PT 101079 A 19940228; SI 9200332 A 19930630; SK 59294 A3 19950208; TW 232697 B 19941021
DOCDB simple family (application)
US 9209845 W 19921119; AU 3136893 A 19921119; CA 2123128 A 19921119; CN 92113215 A 19921123; CZ 124494 A 19921119; EP 92925238 A 19921119; FI 942345 A 19940520; HU 9401350 A 19921119; IL 10381792 A 19921120; JP 50944293 A 19921119; MX 9206628 A 19921118; NO 941905 A 19940520; NZ 24520792 A 19921120; PT 10107992 A 19921119; SI 9200332 A 19921119; SK 59294 A 19921119; TW 81109304 A 19921120