Hideo Tsutsumi

Synthesis of phenyl d-glucopyranosides; nucleophilic substitution of O-(2,3,4,6-tetra-O-benzyl-d-glucopyranosyl)-pseudoureas by phenols

Abstract A series of nucleophilic substitution-reactions of O -(2,3,4,6-tetra- O -benzyl- d -glucopyranosyl)pseudoureas by phenols was investigated as a novel procedure for the synthesis of phenyl d -glucopyranoside derivatives: these reactions were found to give the corresponding phenyl 2,3,4,6-tetra- O -benzyl- d -glucopyranosides in excellent yields. Reaction mechanisms were discussed on the basis of the results obtained.

Syntheses of 1-O-acylaldose derivatives via the corresponding O-glycosylpseudoureas☆

Abstract A series of 1- O -acylaldose derivatives was prepared in good yield through the reaction of 1,3-dialkyl- O -glycosylpseudoureas with carboxylic acids.

Synthesis and antibacterial activity of novel 4-pyrrolidinylthio carbapenems--I. 2-Alkoxymethyl derivatives.

The synthesis and in vitro antibacterial activity of a novel series of 2-alkoxymethyl-4-pyrrolidinylthio-1 beta-methyl carbapenems are described. As a result of these studies, we discovered that FR27743 (19j) containing a novel 2-fluoroethoxymethyl substituent possesses a broad spectrum of antibacterial activity against both Gram-positive and Gram-negative organisms, including Pseudomonas aeruginosa. Furthermore, FR27743 exhibited excellent stability against renal dehydropeptidase-I (DHP-I), good urinary recovery, and superior in vivo activity compared to that for Meropenem against several systemic infections.

Synthesis of protected purpurosamine B and 6-epipurpurosamine B

In relation to the synthesis of antipseudomonal drugs, namely, gentamicin C2 and 3-de-O-methylsporaricin A, a protected purpurosamine B (15) and 6-epipurpurosamine B (13) were synthesized. The key intermediate, methyl 2,3,4,7- tetradeoxy-6-O-(methylsulfonyl)-2-phthalimido-beta-L-lyxo-++ +heptopyranoside (8), was obtained in 48% yield by Grignard addition to methyl 2,3,4-trideoxy-2-phthalimido-alpha-D-erythro-hexodialdo-1,5-pyrano side (7) proceeding in accordance with Crams chelate rule, followed by methylsulfonylation. From 8, compound 15 was readily obtained by introduction of the azide group with inversion of configuration at C-6. Compound 13 was obtained by introduction of the azide group with retention of configuration.

Synthesis and antibacterial activity of novel 4-pyrrolidinylthio carbapenems. Part III:

Abstract The synthesis and biological activity of a novel series of 2-alkyl-4-pyrrolidinylthio-β-methylcarbapenems containing a variety of cationic heteroaromatic substituents is described. As a result of these studies, we uncovered a relationship between in vitro antibacterial activity and the length of the alkyl spacer part, and discovered FR20950 ( 1c ) Download high-res image (74KB) Download full-size image Scheme 3 . Synthetic route to novel carbapenems. Reagents and conditions: (i) NaOMe, MeOH, (or TFA, Et 3 SiH), then 24 , i Pr 2 EtN, DMAC, MeCN; (ii) MeI, Me 2 CO or THF; (iii) ICH 2 CONH 2 , Me 2 CO; (iv) I(CH 2 ) 3 NHAoc, DMF; (v) MeOTf, CH 2 Cl 2 ; (vi) FSO 3 Me, CH 2 Cl 2 ; (vii) Pd(PPh 3 ) 4 , PPh 3 , THF–EtOH, n Bu 3 SnH or morpholine; (viii) Pd(OH) 2 -C, H 2 , THF–phosphate buffer (pH 6.5). , containing a two methylene spacer moiety and an imidazolio group, which possesses a balanced spectrum of antibacterial activity, including Pseudomonas aeruginosa and Methicillin-resistant Staphylococcus aureus (MRSA). Furthermore, FR20950 exhibited excellent urinary recovery, and comparable stability against renal dehydropeptidase-I (DHP-I) to Biapenem. DHP-I stability could be improved by introduction of a substituent on to the imidazole ring.

Synthetic studies with carbonates. Part 10. Reactions of ethylene carbonate with some active methylene compounds catalysed by quaternary ammonium or alkali metal halides

The reaction of ethylene carbonate (1) with pentane-2,4-dione (2) was carried out in the presence of a series of halides as catalysts. As examples, the reaction catalysed by sodium iodide gave 4-oxopentyl acetate (3), and that catalysed by tetraethylammonium chloride gave 2-methyl-2-(2-oxopropyl)-1.3-dioxolan (4), as the predominant product in high yield. Reactions with 1,3-diphenylpropane-1,3-dione (11) in place of (2) showed the same trend. However, reactions with 2-alkyl-1,3-diphenylprop-ane-1,3-diones, (20) and (25), gave no oxoalkyl esters corresponding to (3), but other types of product [(21), (22), and (26)]. In reactions with 3,3-dibenzylpentane-2,4-dione (30), which has no proton dissociable under the conditions used, were obtained 3-benzyl-4-phenylbutan-2-one (31), 2-(2-acetoxyethoxy)-3-benzyl-4-phenylbut-2-ene (32), and 2-hydroxy-ethyl acetate (33). Reaction mechanisms are discussed.Moreover, ethyl acetoacetate (34) anddiethyl malonate (35) gave lactone derivatives, (37) and (39), respectively, but diethyl 2-acetamidomalonate (36) gave ethyl 2-acetamidobutyrate (40), in reactions with (1). Furthermore, the reactions of (1) with the diones (2) and (11) in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) gave the corresponding ethylene acetals (4) and (16), respectively.