New neplanocin analogues. IX. A practical preparation of (6'R)-6'-C-methylneplanocin A (RMNPA), a potent antiviral agent, and the determination of its 6'-configuration. Diastereoselective deamination by adenosine deaminase.
We previously synthesized (6'R)- and (6'S)-6'-C-methylneplanocin A's (2a and 2b, respectively), and found that one of them has a potent antiviral activity, though its 6'-configuration has not been confirmed. This report describes the determination of the 6'-configuration and practical preparation of the antivirally active diastereomer. The 6'-configuration of the active diastereomer was determined as R by the modified Mosher's method as well as by synthesizing 2b from the known cyclopentenone derivative 10. A practical method for preparing the 6'R-diastereomer was developed by using diastereoselective deamination with Ado deaminase as the key step. Treatment of the diastereomeric mixture of 2a and 2b, which was prepared via an addition reaction of Me3Al with the 6'-formyl derivative 3, with Ado deaminase from calf intestine, deaminated 2b selectively to give the corresponding (6'S)-inosine congener 5, and left the desired 2a not deaminated. After silica gel column chromatography, 2a was obtained in a pure form.
Shuto
S
S
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Obara
T
T
Yaginuma
S
S
Matsuda
A
A
D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification; D000243:Adenosine Deaminase / Q000737:chemistry*; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry*; D002850:Chromatography, Gel; D003641:Deamination; D013237:Stereoisomerism
D000998:Antiviral Agents; C075039:6'-C-methylneplanocin A; D000243:Adenosine Deaminase; D000241:Adenosine