Shigeyuki Yoshifuji

Lactams—I : The synthesis and acid hydrolysis of 4- and 5-substituted 1-benzyl-2-piperidone derivatives☆

Abstract In order to explain the difficulty in hydrolysing the lactam linkage of 1-benzyl-2-oxo-5-ethyl-4-piperidineacetic acid (XIV) under acid conditions, several model compounds such as 1-benzyl-2-piperidone (X), 1-benzyl-5-ethyl-2-piperidone (XI), 1-benzyl-4-ethyl-2-piperidone (XII) and 1-benzyl-2-oxo-4-piperidineacetic add (XIII) were prepared and their hydrolysis in boiling 6N HCl was studied. For each of the lactams, the hydrolysis was found to proceed to an equilibrium as shown in Table 1. Substituents at the 4- and 5-positions of the piperidone ring seemed to favour the ring form in the equilibrium between piperidones (X-XIV) and ω-amino acid hydrochlorides (type XV).

Quinolizidines—V : A novel synthetic route to Ipecac alkaloids through chemical incorporation of ethyl cincholoiponate derived from the cinchona alkaloid cinchonine

Abstract A new synthetic route to (−)-emetine (1) and related Ipecac alkaloids has been exploited in terms of the synthesis of the tricyclic ester (−)-30 from ethyl cincholoiponate [(+)-4], a degradation product of the Cinchona alkaloid cinchonine (7). The steps involved are those in the sequence (+)-4→(+)-8→9→10→(−)-12-→(−)-13→ (+)-21→(+)-22→28→29→(−)-30. In the Hg(OAc)2-EDTA oxidation of the amino alcohol 9 to the 6-piperidone 10, the cis- and the trans-2-piperidone isomers 11 were the minor products. The successful conversion of the cis-lactam acid (−)-13 into the trans-lactam acid (+)-21 was effected on the basis of the fact that (±)-13 and (±)-21 are convertible to each other through cis-trans equilibration (13:21 = 33:67) at 180° in 75 min. When this isomerisation step was skipped in the above reaction sequence, the 2,3-cis-tricycle (+)-33, synthetic precursor for chiral 2,3-cis-emetines, was obtained.

Quinolizidines—IV: Total syntheses of (±)-ankorine and (±)-11-methoxyprotoemetinol

Abstract The first total synthesis of ankorine (4) , an Alangium lamarckii alkaloid, has been accomplished in the form of a recemic modification by means of an initial condensation of 2-benzyloxy-3,4-dimethoxyphenacyl bromide with the lactim ether 6 , derived from ethyl (±)- trans -5-ethyl-2-oxo-4-piperidineacetate ( 5 ), and succeeding steps proceeding through the intemediates 7a, 8a, 9a, 10a (X=Cl), 11a , and 12a . A parallel synthetic route starting with 3,4,5-trimethoxyphenacyl bromide and 6 gave (±)-11-methoxyprotoemetinol ( 12c ) via the intermediates 7c, 8c, 9c, 10c (X =I,ClO 4 ), and 11c . The trimethyl ether 12c did not match the O-Me derivative (type 12e ) of natural ankorine. Thus, the formula 4 defines the structure and relative stereochemistry of ankorine.