Susumu Kamata

An efficient and stereocontrolled synthesis of platelet activating factor from (s)-(−)-malic acid

Abstract A stereocontrolled synthesis of C16-PAF ( 11 ) from (S)-(−)-malic acid ( 1 ), employing regioselective hydrogenolytic cleavage of benzylidene acetal derivatives of (S)-1,2,4-butanetriol ( 2 ) with borane-tetrahydrofran complex, is described.

Synthesis and pharmacological properties of ureidomethylcarbamoylphenylketone derivatives. A new potent and subtype-selective nonpeptide CCK-B/gastrin receptor antagonist, S-0509.

A novel series of CCK-B/gastrin receptor antagonists-ureidomethylcarbamoylphenylketone derivatives-were designed, synthesized, and evaluated for activity. Structure-activity relationship studies revealed the importance of a carboxylic acid at substituent R2 and tert-butoxycarbonyl group at R1 in structure A. Compound 7a (S-0509) showed remarkable affinity for the CCK-B/gastrin receptor and a subtype selectivity profile in vitro. Administration (id) of 7a led to excellent inhibition of gastric acid secretion induced by pentagastrin in anesthetized rats with an ED50 value of 0.014 mg/kg. Furthermore, 7a proved to have poor blood-brain permeability by its small effect on enhancement of morphine analgesia. Thus, S-0509 has an increase in selectivity for the peripheral effects of gastrin antagonism from the central effects of CCK-B antagonism.

Potent and subtype-selective CCK-B/gastrin receptor antagonists: 2,4-dioxo-1,5-benzodiazepines with a plane of symmetry

A series of CCK-B/gastrin receptor antagonists, 2,4-dioxo-1,5-benzodiazepine derivatives with a plane of symmetry, were designed, synthesized, and evaluated for antagonistic activity. Structure-activity relationship studies revealed that carbonylmethyl groups at both N-1 and N-5 positions and hydrophilic groups, such as the carboxyl group on the benzene ring attached to the ureido group at the C-3 position, brought about potent affinity and subtype selectivity for CCK-B/gastrin receptors. Several compounds showed excellent in vivo inhibition of gastric acid secretion induced by pentagastrin in anesthetized rats.

One-step synthesis of oxazolinoazetidinones from penicillin sulfoxides: potential intermediates for 1-oxacephem synthesis

Abstract Reaction of penicillin sulfoxides with a tervalent phosphorous compound in the presence of a catalytic amount of squaric acid gave oxazolinoazetidinones, potential intermediates for synthesis of 1-oxacephems, in good yields.2β-Chloromethyl- and 6α-methoxypenicillin sulfoxides also undergo this reaction. The reaction contrasts with the well-known Cooper reaction which usually gives thiazolinoazetidinones.

Activity of synthetic gibberellin A15 and (±)-gibberellin A15isolactone

The activities of (±)-gibberellin A15 ((±)-GA15) and (±)-gibberellin A15-isolactone ((±)-iso-GA15) which were obtained by stereocontrolled total synthesis and gibberellin A15 (E-GA15) synthesized by interconversion of enmein were assayed by the rice seedling test. As expected, (±)-GA15 showed half the activity of natural gibberellin A15 (GA15). E-GA15 which has a natural configuration showed the same activity as natural gibberellin A15 while (±)-iso-GA15 was almost inactive. These samples were also submitted to the cucumber hypocotyl assay. Contrary to what has already been reported, they were almost inactive.

Stability problem of the 4-hydroxy-azetidin-2-one system, a possible intermediate in 1-oxacephem synthesis

Reduction of the 4-hydroperoxy-azetidin-2-one (4) at –50 °C gave the 4-hydroxy-azetidin-2-one (6) which was converted into the corresponding trifluoroacetate (7); the 4-hydroxy-azetidin-2-ones, which were not isolated, were unstable at room temperature, and appeared to be unpromising as intermediates for 1-oxacephem synthesis.