e.g. Filippa Pettersson or Cancer Res. 75(6) , 1102-12, (2015) or 10.1002/anie.201600521

An efficient route to all eight stereoisomers of a tri-functionalised cyclopentane scaffold for drug discovery

…, SJC Taylor, DA Chaplin, G Casy, R McCague

Index: Smith, Mark E.B.; Lloyd, Michael C.; Derrien, Nadine; Lloyd, Richard C.; Taylor, Stephen J.C.; Chaplin, David A.; Casy, Guy; McCague, Raymond Tetrahedron Asymmetry, 2001 , vol. 12, # 5 p. 703 - 705

Full Text: HTML

Citation Number: 21

Abstract

3-(tert-Butoxycarbonylamino)-4-hydroxycyclopentanecarboxylic acid methyl esters are conformationally rigid and potentially valuable scaffolds for pharmaceutical discovery. 1 We have recently described an approach to these targets that is primarily concerned with the selectivity of hydrogenation reactions on cyclopent-1-enecarboxylate intermediates. 2 Epoxidations with Oxone® were employed to introduce the oxygen functionality, but we encountered poor volume efficiency and low ...

Methyl chloroformate Structure

Methyl chloroformate

(1S,3R,4S)-3-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-4-hydroxycyclopentanecarboxylic acid Structure

(1S,3R,4S)-3-({...

~93%

methyl (1S,3R,4S)-3-{[(tert-butoxy)carbonyl]amino}-4-hydroxycyclopentane-1-carboxylate Structure

methyl (1S,3R,4...

(1R-4S)-4-[[(1,1-dimethylethoxy)carbonyl]amino]- 2-Cyclopentene-1-carboxylic acid methyl ester Structure

(1R-4S)-4-[[(1,...

~%

methyl (1R,3S,4S)-3-{[(tert-butoxy)carbonyl]amino}-4-hydroxycyclopentane-1-carboxylate Structure

methyl (1R,3S,4...

(3R,4S)-4-tert-butoxycarbonylamino-3-hydroxycyclopent-1-enecarboxylic acid Structure

(3R,4S)-4-tert-...

~%

methyl (1R,3S,4S)-3-{[(tert-butoxy)carbonyl]amino}-4-hydroxycyclopentane-1-carboxylate Structure

methyl (1R,3S,4...

(1R,4S)-4-Aminocyclopent-2-enecarboxylicacid Structure

(1R,4S)-4-Amino...

~%

methyl (1R,3S,4S)-3-{[(tert-butoxy)carbonyl]amino}-4-hydroxycyclopentane-1-carboxylate Structure

methyl (1R,3S,4...

2-Azabicyclo[2.2.1]hept-5-en-3-one Structure

2-Azabicyclo[2....

~%

methyl (1R,3S,4S)-3-{[(tert-butoxy)carbonyl]amino}-4-hydroxycyclopentane-1-carboxylate Structure

methyl (1R,3S,4...

methyl (1R,3S,4R)-3-{[(tert-butoxy)carbonyl]amino}-4-hydroxycyclopentane-1-carboxylate Structure

methyl (1R,3S,4...

~%

methyl (1R,3S,4S)-3-{[(tert-butoxy)carbonyl]amino}-4-hydroxycyclopentane-1-carboxylate Structure

methyl (1R,3S,4...

(1R,3S,4R)-3-((tert-Butoxycarbonyl)amino)-4-hydroxycyclopentane-1-carboxylic acid Structure

(1R,3S,4R)-3-((...

~%

methyl (1R,3S,4S)-3-{[(tert-butoxy)carbonyl]amino}-4-hydroxycyclopentane-1-carboxylate Structure

methyl (1R,3S,4...

(1R-4S)-4-[[(1,1-dimethylethoxy)carbonyl]amino]- 2-Cyclopentene-1-carboxylic acid methyl ester Structure

(1R-4S)-4-[[(1,...

~%

(1S,2S,4S)-N-BOC-1-AMINO-2-HYDROXYCYCLOPENTANE-4-CARBOXYLIC ACID METHYL ESTER Structure

(1S,2S,4S)-N-BO...

(3R,4S)-4-tert-butoxycarbonylamino-3-hydroxycyclopent-1-enecarboxylic acid methyl ester Structure

(3R,4S)-4-tert-...

~%

(1S,2S,4S)-N-BOC-1-AMINO-2-HYDROXYCYCLOPENTANE-4-CARBOXYLIC ACID METHYL ESTER Structure

(1S,2S,4S)-N-BO...

(3R,4S)-4-tert-butoxycarbonylamino-3-hydroxycyclopent-1-enecarboxylic acid Structure

(3R,4S)-4-tert-...

~%

(1S,2S,4S)-N-BOC-1-AMINO-2-HYDROXYCYCLOPENTANE-4-CARBOXYLIC ACID METHYL ESTER Structure

(1S,2S,4S)-N-BO...

methyl (1S,3R,4S)-3-hydroxy-4-[(2-methylpropan-2-yl)oxycarbonylamino]cyclopentane-1-carboxylate Structure

methyl (1S,3R,4...

~%

(1S,2S,4S)-N-BOC-1-AMINO-2-HYDROXYCYCLOPENTANE-4-CARBOXYLIC ACID METHYL ESTER Structure

(1S,2S,4S)-N-BO...

(1R,4S)-4-Aminocyclopent-2-enecarboxylicacid Structure

(1R,4S)-4-Amino...

~%

(1S,2S,4S)-N-BOC-1-AMINO-2-HYDROXYCYCLOPENTANE-4-CARBOXYLIC ACID METHYL ESTER Structure

(1S,2S,4S)-N-BO...

2-Azabicyclo[2.2.1]hept-5-en-3-one Structure

2-Azabicyclo[2....

~%

(1S,2S,4S)-N-BOC-1-AMINO-2-HYDROXYCYCLOPENTANE-4-CARBOXYLIC ACID METHYL ESTER Structure

(1S,2S,4S)-N-BO...

4-[[(1,1-DIMETHYLETHOXY)CARBONYL]AMINO]-2-CYCLOPENTENE-1-CARBOXYLIC ACID METHYL ESTER Structure

4-[[(1,1-DIMETH...

~%

(1R,2S,4R)-N-BOC-1-AMINO-2-HYDROXYCYCLO-PENTANE-4-CARBOXYLIC ACID METHYL ESTER Structure

(1R,2S,4R)-N-BO...

2H-Cyclopentoxazole-5-carboxylic acid, 6-bromohexahydro-2-oxo-, methyl ester, (3aR,5R,6R,6aR)- Structure

2H-Cyclopentoxa...

~%

(1R,2S,4R)-N-BOC-1-AMINO-2-HYDROXYCYCLO-PENTANE-4-CARBOXYLIC ACID METHYL ESTER Structure

(1R,2S,4R)-N-BO...

(3S,4R)-4-tert-butoxycarbonylamino-3-hydroxycyclopent-1-enecarboxylic acid Structure

(3S,4R)-4-tert-...

~%

(1R,2S,4R)-N-BOC-1-AMINO-2-HYDROXYCYCLO-PENTANE-4-CARBOXYLIC ACID METHYL ESTER Structure

(1R,2S,4R)-N-BO...

methyl (1S,3R,4R)-3-acetoxy-4-((tert-butoxycarbonyl)amino)cyclopentane-1-carboxylate Structure

methyl (1S,3R,4...

~98%

(1R,2R,4S)-N-BOC-1-AMINO-2-HYDROXYCYCLO-PENTANE-4-CARBOXYLIC ACID METHYL ESTER Structure

(1R,2R,4S)-N-BO...

4-[[(1,1-DIMETHYLETHOXY)CARBONYL]AMINO]-2-CYCLOPENTENE-1-CARBOXYLIC ACID METHYL ESTER Structure

4-[[(1,1-DIMETH...

~%

(1R,2R,4S)-N-BOC-1-AMINO-2-HYDROXYCYCLO-PENTANE-4-CARBOXYLIC ACID METHYL ESTER Structure

(1R,2R,4S)-N-BO...

2H-Cyclopentoxazole-5-carboxylic acid, 6-bromohexahydro-2-oxo-, methyl ester, (3aR,5R,6R,6aR)- Structure

2H-Cyclopentoxa...

~%

(1R,2R,4S)-N-BOC-1-AMINO-2-HYDROXYCYCLO-PENTANE-4-CARBOXYLIC ACID METHYL ESTER Structure

(1R,2R,4S)-N-BO...

(3S,4R)-4-tert-butoxycarbonylamino-3-hydroxycyclopent-1-enecarboxylic acid Structure

(3S,4R)-4-tert-...

~%

(1R,2R,4S)-N-BOC-1-AMINO-2-HYDROXYCYCLO-PENTANE-4-CARBOXYLIC ACID METHYL ESTER Structure

(1R,2R,4S)-N-BO...

(1S,4R)-Methyl 4-aminocyclopent-2-enecarboxylate hydrochloride Structure

(1S,4R)-Methyl ...

~%

(1R,2R,4S)-N-BOC-1-AMINO-2-HYDROXYCYCLO-PENTANE-4-CARBOXYLIC ACID METHYL ESTER Structure

(1R,2R,4S)-N-BO...

methyl (1S,3R,4S)-3-{[(tert-butoxy)carbonyl]amino}-4-hydroxycyclopentane-1-carboxylate Structure

methyl (1S,3R,4...

~%

(1R,2R,4S)-N-BOC-1-AMINO-2-HYDROXYCYCLO-PENTANE-4-CARBOXYLIC ACID METHYL ESTER Structure

(1R,2R,4S)-N-BO...

(1S,3R,4S)-3-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-4-hydroxycyclopentanecarboxylic acid Structure

(1S,3R,4S)-3-({...

~%

(1R,2R,4S)-N-BOC-1-AMINO-2-HYDROXYCYCLO-PENTANE-4-CARBOXYLIC ACID METHYL ESTER Structure

(1R,2R,4S)-N-BO...

(1R-4S)-4-[[(1,1-dimethylethoxy)carbonyl]amino]- 2-Cyclopentene-1-carboxylic acid methyl ester Structure

(1R-4S)-4-[[(1,...

~%

methyl (1S,3R,4S)-3-hydroxy-4-[(2-methylpropan-2-yl)oxycarbonylamino]cyclopentane-1-carboxylate Structure

methyl (1S,3R,4...

(3R,4S)-4-tert-butoxycarbonylamino-3-hydroxycyclopent-1-enecarboxylic acid Structure

(3R,4S)-4-tert-...

~%

methyl (1S,3R,4S)-3-hydroxy-4-[(2-methylpropan-2-yl)oxycarbonylamino]cyclopentane-1-carboxylate Structure

methyl (1S,3R,4...

(1R,4S)-4-Aminocyclopent-2-enecarboxylicacid Structure

(1R,4S)-4-Amino...

~%

methyl (1S,3R,4S)-3-hydroxy-4-[(2-methylpropan-2-yl)oxycarbonylamino]cyclopentane-1-carboxylate Structure

methyl (1S,3R,4...

2-Azabicyclo[2.2.1]hept-5-en-3-one Structure

2-Azabicyclo[2....

~%

methyl (1S,3R,4S)-3-hydroxy-4-[(2-methylpropan-2-yl)oxycarbonylamino]cyclopentane-1-carboxylate Structure

methyl (1S,3R,4...

(1R,4S)-4-Aminocyclopent-2-enecarboxylicacid Structure

(1R,4S)-4-Amino...

~%

(1R-4S)-4-[[(1,1-dimethylethoxy)carbonyl]amino]- 2-Cyclopentene-1-carboxylic acid methyl ester Structure

(1R-4S)-4-[[(1,...