NEW NEPLANOCIN ANALOGS .9. 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 anti viral activity, though its 6'-configuration has not been confirmed, Th is report describes the determination of the 6'-configuration and prac tical preparation of the antivirally active diastereomer. The 6'-confi guration of the active diastereomer was determined as R by the modifie d Mosher's method as well as by synthesizing 2b from the known cyclope ntenone derivative 10, A practical method for preparing the 6'R-diaste reomer 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 Me(3)Al with the 6'-formyl derivative 3, with Ado deaminase from calf intestine, d eaminated 2b selectively to give the corresponding (6'S)-inosine conge ner 5, and left the desired 2a not deaminated, After silica gel column chromatography, 2a was obtained in a pure form.