Industrial Biotransformations

-Lactamase
Pseudomonas solanacearum
4) Process parameters
conversion: 55 %
yield: 45 %
selectivity: 82%
ee: > 98 %
reactor type: batch
capacity: ton scale
residence time: 3 h
down stream processing: harvesting cells, extraction of product with dichloromethane
production site: Celltech Group plc, U.K.
company: Celltech Group plc, U.K.
5) Product application
● The lactam can be converted to carbovir:
O
1
NH
● Carbovir is a potent and selective inhibitor of HIV-1.
● Its ability to inhibit infectivity and replication of the virus in human T-cell lines at concentrations
200–400 fold below toxic levels makes carbovir a promising candidate for development as
a potential antiretroviral agent.
6) Literature
1) HCl, H2O
2) (MeO) 2CMe2, MeOH, HCl
3) Ac2O, pyridine, CH2Cl2
4) Ca(BH4)2, THF
HO
1 = 2-azabicyclo[2.2.1]hept-5-en-3-one
2 = N-(4-hydroxymethyl-cyclopent-2-enyl)-acetamide
3 = carbovir
Fig. 3.5.2.6 – 2
2
1) HCl, H2O, EtOH
2) 2-amino-4,6-dichloropyrimidine,
NHAc Pri 2NEt, BunOH + - 3) 4-ClC6H4N2 Cl , HOAc, NaOAc, H2O
4) Zn, AcOH, EtOH, H2O
5) (EtO) 3CH, HCl, H2O
6) NaOH,H2O
EC 3.5.2.6
● Taylor, S.J.C., Sutherland, A.G., Lee, C., Wisdom, R., Thomas, S., Roberts, S.M., Evans, C.
(1990) Chemoenzymatic synthesis of (–)-carbovir utilizing a whole cell catalyzed resolution of
2-azabicyclo[2.2.1]hept-5-en-3-one, J. Chem. Soc., Chem. Commun., 1120–1121
● Taylor, S.J.C., McCague, R. (1997) Resolution of the carbocyclic nucleoside synthon 2-azabicyclo[2.2.1]hept-5-en-3-one
with lactamses, in: Chirality In Industry II (Collins, A.N., Sheldrake,
G.N. and Crosby, J., eds.), pp. 184–190, John Wiley & Sons, New York
HO
3
N
N
O
N
NH
NH2
423