Makoto Takemura

Biotransformation of reticuline into coreximine, scoulerine, pallidine, and isoboldine with rat liver enzyme

Abstract (±)-Reticuline ( 1 ) was biotransformed into the protoberberine alkaloids, coreximine ( 12 ) and scoulerine ( 10 ), the morphinandienone alkaloid, pallidine ( 14 ), and the aporphine alkaloid, isoboldine ( 16 ). The transformation was stimulated by O 2 and the cofactor NAD, NADP, or NADPH, NADPH being more effective than the other cofactors. The N -methyl group of (±)-reticuline was not incorporated intact into protoberberines.

Practical Synthesis of DQ-113, a New Quinolone Antibacterial Agent, by Using the Intramolecular Horner-Wadsworth-Emmons Reaction

A practical route was developed for synthesizing the C-7 substituent of DQ-113 (6, 5-amino-7-[(3S,4R)-4-(1-aminocycloprop-1-yl)-3-fluoropyrrolidin-1-yl]-6-fluoro-1-[(1R,2S)-2-fluorocyclopropan-1-yl]-1,4-dihydro-8-methyl-4-oxoquinolin-3-carboxylic acid), a new quinolone antibacterial agent for serious infections caused by Gram-positive pathogens. The key step was the intramolecular Homer-Wadsworth-Emmons reaction. In addition, the yield of the final aromatic nucleophilic substitution reaction was improved.

Synthesis of potentially useful intermediates for 1-fluorocarbapenems

The displacement reaction of the 4-acetoxyazetidin-2-one (6) with dimethyl fluoromalonate was readily performed in the presence of lithium hexamethyldisilazide. The product (7), quantitatively obtained, was converted into two potential synthetic intermediates (4) and (5) of 1-fluorocarbapenem derivatives

Studies on the syntheses of heterocyclic compounds. Part 682. Six new isoquinoline alkaloids from Corydalis ochotensis var. raddeana

Separation of the alkaloids from Corydalis ochotensis yielded six new isoquinoline alkaloids, raddeanamine (1), raddeanine (2), raddeanidine (3), raddeanone (4), aobamine (5), and aobamidine (6), along with the known alkaloids protopine (7), adlumidine(8), bicuculline (9), dihydrosanguinarine (10), ochotensimine (11), ochotensine (12), cheilanthifoline (13), scoulerine (14), sinoacutine (15), and pallidine (16).

Studies on the syntheses of heterocyclic compounds. Part DXCVII. Novel formation of benzo[5,6]cyclohept[1,2,3-ij]isoquinolines from berbinium salts

Heating coreximine methiodide (5) with methanolic potassium hydroxide solution gave the secoberbine (13) and 1,2,3,7,12,12a-hexahydro-6,10-dihydroxy-5,9-dimethoxybenzo[5,6]cyclohept[1,2,3-ij]isoquinoline (14). The latter was converted into its OO-dimethyl ether (16), which was also synthesised from laudanosine (18) with formalin in the presence of hydrochloric acid. Treatment of the monophenolic secoberbine (12) with acid gave the corresponding benzocycloheptisoquinoline.

Studies on the syntheses of heterocyclic compounds. Part DLXXVII. An abnormal Hofmann degradation of phenolic berbinium salts

Hofmann degradation of 11-hydroxy-10-methoxy-7-methyl-2,3-methylenedioxyberbinium iodide (2) with methanolic potassium hydroxide gave 1,2,3,4-tetrahydro-1-(5-hydroxy-4-methoxy-2-methoxymethylbenzyl)-6,7-methylenedioxy-2-methylisoquinoline (14) in addition to the normal methine base (7). Abnormal Hofmann degradation was observed with schefferine methiodide (3) and nandinine methiodide (4). The mechanism of this type of reaction and the biogenesis of the protoberberine alkaloid mecambridine (22) are discussed.