Enhanced enzymatic synthesis of the enantiopure intermediate for the blockbuster drug intermediate abacavir through a two-step enzymatic cascade reaction
A very efficient enzymatic two-step cascade reaction was devised (E > 200) for the resolution of activated gamma-lactams (+/-)-1 and (+/-)-2. The N-hydroxymethyl group worked as a traceless activating group, when the reactions were performed with H2O (0.5 equiv) in the presence of benzylamine (1...
Elmentve itt :
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2016
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| Sorozat: | TETRAHEDRON-ASYMMETRY
27 No. 16 |
| doi: | 10.1016/j.tetasy.2016.06.019 |
| mtmt: | 3153459 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/10563 |
| Tartalmi kivonat: | A very efficient enzymatic two-step cascade reaction was devised (E > 200) for the resolution of activated gamma-lactams (+/-)-1 and (+/-)-2. The N-hydroxymethyl group worked as a traceless activating group, when the reactions were performed with H2O (0.5 equiv) in the presence of benzylamine (1 equiv) in i-Pr2O at 60 degrees C. The ring-opened enantiomerically pure gamma-amino acids (1S,4R)-6 (ee = 99%, intermediate of abacavir) and (1S,3R)-8 (ee = 99%) and unreacted lactams (1S,4R)-1 and (1R,4S)-2 (ee >= 96%) were obtained in good yields (>= 43%). Treatment of (1S,4R)-1 and (1R,4S)-2 with 18% HCl or NH4OH resulted in (1R,4S)-6 center dot HCl and (1S,3R)-8 center dot HCI or (15,4R)-3 and (1R,4S)-4 quantitatively, with ee >= 96%. (C) 2016 Elsevier Ltd. All rights reserved. |
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| Terjedelem/Fizikai jellemzők: | 729-731 |
| ISSN: | 0957-4166 |