51(PA1-9) 触媒的不斉水素化反応に基づくモルヒネおよびその関連体の合成(ポスター発表の部)

概要

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The newly elaborated Ru(OCOCH_3)_2[(R)-binap] complex catalyze the enantioselective hydrogenation of (Z)-N-formyl-1-alkylidene-1,2,3,4-tetrahydroisoquinolines to give the corresponding (R)-N-formyl-1-alkyl-1,2,3,4-tetrahydroisoquinolines in high (>95%) enantiomeric purity, realizing efficient entry to naturally occurring morphine via norreticuline and Beyerman's or Rice's intermediate. This homogeneous hydrogenation method has been successfully extended to the asymmetric synthesis of clinically important artificial morphines. For instance, (Z)-N-formyl-2-(4-methoxyphenylmethylene)-3,4-dimethyl-1,2,5,6-tetrahydropyridine and (Z)-N-formyl-1-(4-methoxyphenylmethylene)-1,2,3,4,5,6,7,8-octahydroisoquinoline are hydrogenated with a catalytic amount of Ru(OCOCF_3)_2(tolbinap), affording the enantiomeric precursors of benzomorphans or morphinans. The ruthenium-catalyzed hydrogenation is completely regioselective; the enamide moiety is saturated, whereas the tetrasubstituted olefinic bond remains intact. These compounds are convertible to both enantiomers of the morphine analogues in optically pure form by the standard Grewe cyclization followed by removal and/or modification of the N-formyl group and recrystallization. Metazocine, pentazocine (potent but nonaddictive narcotic analgesics), dextromethorphan (powerful antitussive agent), etc., are obtainable via such intermediates.
1987-07-25