2-Chloroadenine → Cladribine
Reaction equation
[C@@H]1(N2C3N=C(N)NC(=O)C=3N=C2)O[C@H](CO)C[C@H]1O.[C@@H:20]1(N2C3N=C(N)NC(=O)C=3N=C2)[O:27][C@H:24]([CH2:25][OH:26])[C@@H:22]([OH:23])[CH2:21]1.[Cl:39][C:40]1[N:48]=[C:47]2[C:43]([NH:44][CH:45]=[N:46]2)=[C:42]([NH2:49])[N:41]=1>>[CH2:21]1[C@H:20]([N:46]2[C:47]3[N:48]=[C:40]([Cl:39])[N:41]=[C:42]([NH2:49])[C:43]=3[N:44]=[CH:45]2)[O:27][C@H:24]([CH2:25][OH:26])[C@H:22]1[OH:23]Participants
Procedure
Stereoselective glycosylation of sodium salts of halopurines and analogues with 2-deoxy-3,5-di-O-p-toluoyl-α-D-erythro-pentofuranosyl chloride gave β-nucleoside anomers via predominant Walden inversion,17,18 and ammonolysis/deprotection gave CldAdo.19 Although the sodium salt glycosylation usually gave good anomeric stereoselectivity, minor quantities of α anomers and >10% of N7 regioisomers were usually formed.20,21 This requires separations and results in diminished yields of the desired N9 product. Carson et al.1 had reported an enzymatic transfer of the 2-deoxy sugar from thymidine to 2-chloroadenine (ClAde). Holy and coworkers noted that cells of a strain of Escherichia coli performed glycosyl transfer from 2′-deoxyuridine to 2-chloro-6-[(dimethylaminomethylene)amino]purine to give a derivative of CldAdo.22 Very recently Barai, Mikhailopulo, and coworkers23 described an E. coli-mediated glycosyl transfer synthesis of 2,6-diamino-9-(3-deoxy-β-D-erythro-pentofuranosyl)purine,24 and its enzymatic deamination to 3′-deoxyguanosine.24 They reported glycosyl transfer from 2′-deoxyguanosine to ClAde, and claimed a yield of 81% of CldAdo (based on ClAde).23 However, a 3:1 ratio of dGuo/ClAde was employed, so the yield of CldAdo was <27% based on dGuo.
Sources & evidence
- ORD record
- ord-25b7343cae524a29a80344ab973965df
- Source dataset
- uspto-grants-2009_08
- Patent number
- US07572909B2
Reaction notes
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