Takanori Miyashita

Synthesis of optically active aporphine and morphinandienone alkaloids via p-quinol esters

Lead tetraacetate oxidation of N-trifluoroacetylnorcodamine (5) in (S)-(+)-2-phenylpropionic acid gave a diastereomeric mixture of two p-quinol acylates, which were easily separated to enantiomerically pure 6a and 6b. Treatment of the chiral quinol acylates (6a) and (6b) with trifluoroacetic acid in CH2Cl2 at room temperature afforded (1R)-(−)-6-trifluoroacetylwilsonirine (7a) and (1S)-(+)-(7b), respectively. Saponification of 7a and 7b gave rise to (−)-wilsonirine (8a) and its enantiomer (8b), respectively. Similarly, (−)-nordomesticine (12a) and (+)-(12b) were synthesized in enantiomerically pure form from 10a and 10b. On the other hand, acid treatment of 6a and 6b in CH3CN at lower temperature (−30 °C) followed by N-deprotection gave the corresponding normorphinandienones (15a and 15b) as major products, which were transformed to enantiomerically pure (−)-16a and (+)-sebiferine (16b). In a similar sequence of reactions, (+)-amurine (19a) and its enantiomer (19b) were synthesized.

First synthesis of L-enantio-uracil dinucleotide

L-Enantio-uracil dinucleotide, which consists of two L-uridylic acids and one pyrophosphate, was synthesized for the first time in our laboratory. Benzolyated L-uridine was prepared by a steroselective glycosylation of silylated uracil with L-1-acetoxy-2,3,5-tri-O-benzoylribose (L-ABR). After deprotection, L-uridine was converted to L-UP4U by the treatment of L-UMP morpholidate with triethyammonium pyrophosphate (TEA-PPi). Spectral data of synthesized L-UP4U are given in a reference. All spectral data were identical with those of the D-enantiomer except the optical rotation. It showed a positive value compared to the D-enantiomer having a negative value.

A fragmentation reaction of 4a-acetoxy-6-methoxy-2-methyl-7-oxo-1,2,3,4,4a,7-hexahydroisoquinoline

Treatment of the p-quinol acetate (1) with boiling MeOH in the presence of BF3·Et2O gave the 8-hydroxy-5,7-dimethoxytetrahydroisoquinoline (2). A mechanism via the phenethylammonium intermediate (10) was proposed.