Takao Izawa

Total syntheses of makaluvamines A, B, C, D and E, cytotoxic pyrroloiminoquinone alkaloids isolated from marine sponge bearing inhibitory activities against topoisomerase II

Abstract Syntheses of makaluvamines A, B, C, D and E (1 – 5), new members of tetrahydropyrroloiminoquinone alkaloids, have been successfully carried out. Particularly, olefin introduction for makaluvamines B and E could be achieved by Pd - mediated and E2 type methodologies.

Total syntheses of makaluvamines A, B, C and D, metabolites of the Fijian sponge Zyzza cf. marsailis exhibiting inhibitory activities against topoisomerase II

Abstract Total syntheses of the tetrahydropyrroloquinoline-alkaloids, makaluvamines A, B, C and D (1, 2, 3 and 4) have successfully been carried out starting from the appropriate derivatives (5, 8 and 10).

Enantiospecific synthesis of [(2′S, 3′S)-bis(hydroxymethyl)azetidin-1-yl] pyrimidine nucleosides as potential antiviral agents☆

Abstract The enantiospecific synthesis of [(2′S, 3′S)-bis(hydroxymethyl)azetidin-1-yl]pyrimidine nucleosides 22, 25, and 27 was achieved via construction of the base on the 1-aminoazetidine 18 prepared from (+)-diethyl-L-tartrate, and they are the first members of a new class of nucleoside analogs in which the oxetane ring in oxetanocin-A 4 is replaced by an azetidine ring linked to a nucleic base through an NN bond.

Enantiomerically pure synthesis and antiviral evaluation of [(2′S, 3′S)-bis(hydroxymethyl)azetidin-1-yl] purine nucleosides: Analogs of oxetanocin-A

Abstract The enantiomerically pure synthesis of [(2′ S , 3′ S )-bis(hydroxymethyl)azetidin-1-yl] adenine 9 and -guanine 13 was achieved via construction of the base on the 1-amino-azetidine 4 and their anti-HSV-1 and -2, and anti-HIV-1 activities were evaluated.

Synthesis of carbocyclic nucleosides: synthesis of (±)-2,2-bis(hydroxymethyl)cyclopropyl nucleosides

Treatment of 2,2-bis(benzyloxymethyl)cyclopropanecarboxylic acid 8 with ethyl chloroformate and sodium azide followed by thermolysis of the resulting keto azide 9 at 80 °C provided the corresponding isocyanate 10, which was then converted into 2,2-bis(benzyloxymethyl)cyclopropylurea 11 and 2,2-bis(benzyloxymethyl)cyclopropylamine 13. The racemic 2,2-bis(hydroxymethyl)cyclopropylpyrimidine nucleosides 16, 21, 22, 23, 26, 29, and 31 and the purine nucleosides 39 and 41 were prepared from compounds 11 and 13, respectively; they showed no antiviral activity against HSV-1, HSV-2, HCMV, and HIV-1 in cell culture.

A facile enantioselective synthesis of (1R, 2R, 3S)-1-amino-2,3-bishydroxymethylcyclobutane derivatives, a key synthetic intermediate of carbocyclic oxetanocins

Abstract (1 R 2 R ,3 S )-1-Amino-2,3-bishydroxymethylcyclobutane derivatives ( 14, 15 ) have been synthesized enantioselectively by [2+3] formation of a cyclopentane ring from (−)-dimenthyl succinate and 3-chloro-2-(chloromethyl)-1-propene and the subsequent ring contraction by the Wolff rearrangement, and the Curtius reaction.

Design and synthesis of an antitumor prodrug released by the reaction with sulfhydryl compounds

Abstract The design and synthesis of carbamate-daunomycin prodrug 11 that can release free daunomycin by the reaction with sulfhydryl compounds is described. The compound 11 is more sensitive to adriamycinresistant L1210 cell line than free daunomycin with relative resistance of 3.7 and 9.2, respectively.

Synthesis and antiviral evaluation of [(2′S, 3′S)-bis(hydroxymethyl)azeitidin-1-yl]pyrimidine nucleosides: analogs of oxetanocin-A

Abstract The enantiospecific synthesis of [(2′S, 3′S)-bis(hydroxymethyl)azetidin-1-yl]pyrimidine nucleosides 15, 18, and 20, the first members of a new class of nucleoside analogs in which the oxetane ring in oxetanocin-A 1 is replaced by an azeitidine ring linked to a nucleic base through an NN bond, was achieved via construction of the base on the 1-aminoazetidine 11 prepared from (+)-dieethyl- l -tartrate. None of these compounds had significant antiviral activity in cell culture tests.

Synthesis and antiviral activity of alkylphosphonic acid derivatives of oxetanocin-A

Abstract A series of phosphonoalkyl derivatives of antiviral antibiotics oxetanocin-A 2 were synthesized and tested in vitro for anti-HSV-1, HSV-2, and anti-HIV-1 activity.

Synthesis of (t-2-benzyloxymethyl-t-3-hydroxy-r-1-methoxycarbonyl)-tetrahydrofuran from an arabino-lactone triflate with K2CO3–MeOH

The arabino-lactone triflate 4 reacts with K2CO3 in MeOH to give the oxetane ester 5 and the tetrahydrofuran ester 6 in a ratio dependent upon the reaction temperature.