Masuo Funabashi

Stereoselective and Efficient Total Synthesis of Optically Active Tetrodotoxin from d-Glucose

A stereoselective and efficient total synthesis of optically active tetrodotoxin (TTX) is described. A polyfunctionalized key cyclitol compound containing branched-chains for the synthesis of TTX was prepared from D-glucose employing the Henry reaction (Nitro aldol reaction) as the key transformation. Stereoselective construction of the alpha-azido-aldehyde branched-chain was achieved via the key spiro alpha-chloroepoxide intermediate.

Branched-chain sugars : VII. Determination of the configuration of L-vinelose by synthesis

Abstract The configuration of L-vinelose was unequivocally determined to be 6-deoxy-3-C-methyl-2-O-methyl- l -talose by comparing an authentic specimen with the synthetic product obtained in eleven steps from 1,2:5,6-di-O-isopropylidene-3-C-methyl-α- d -allofuranose.

New syntheses of methyl 4,6-O-benzylidene-2-deoxy-3-C-methyl-α-d-arabino-hexopyranoside and its conversion into d-evermicose

Abstract Methyl 4,6- O -benzylidene-2-deoxy-3- C -methyl-α- d - arabino -hexopyranoside ( 4 ) was prepared from methyl 4,6- O -benzylidene-2,3-dideoxy-3- C -methylene-α- d -erythro-hexopyranoside ( 1b ) and from methyl 4,6- O -benzylidetic-3 C -methyl-α- d - gluco -hexopyranoside ( 6a ) by two different methods. Synthesis of d -evermicose‡ ( 10 (2,6-dideoxy-3- C -methyl- d -arabino-hexose) was then achieved in four steps from 4 .

Synthesis of l-nogalose and its enantiomer☆

Abstract l -nogalose (6-deoxy-3- C -methyl-2,3,4-tri- O -methyl-L-mannopyranose) and its enantiomer were synthesized via ( a ) introduction of the C -methyl branch by successive epoxidation and reduction of methyl 3,6-dideoxy-2,4-di- O -methyl-3- C -methylene-α- l - arabino -hexopyranoside, and ( b ) deoxygenation at C-6 of methyl 4,6- O -benzylidene-3- C -methyl-2- O -methyl-α-D-mannopyranoside, and O -methylation of the product.

Branched-chain sugars. Part 15. Synthesis of 1L-(1,2,3′,4,5/3,6)-3-hydroxymethyl-4,5-O-isopropylidene-3,3′-O-methylene-6-nitro-2,3,4,5-tetrahydroxycyclohexenecarbaldehyde dimethyl acetal, a potential key compound for total synthesis of optically active tetrodotoxin

The Michael addition of 2-lithio-1,3-dithian to 5,6-dideoxy-3-C-hydroxymethyl-1,2-O-isopropylidene-3,3′-O-methylene-6-nitro-α-D-xylo-hex-5-enofuranose (6) obtained in seven steps from 3-deoxy-1,2:5,6-di-O-isopropylidene-3-C-methylene-α-D-ribo-hexofuranose gave 5,6-dideoxy-5-C-(1,3-dithian-2-yl)-3-C-hydroxymethyl-1,2-O-isopropylidene-3,3′-O-methylene-6-nitro-α-D-glucofuranose (7) and -β-L-idofuranose (8)[(7) : (8)= 5 : 4] in ca. 60% yield. Intramolecular cyclization of both compounds after removal of the isopropylidene group gave branched-chain cyclitols with the muco-configuration (9)[from (7)] and the myo-configuration (13)[from (8)] respectively. The cyclitol (9) was easily converted into the desired title compound (12) in excellent yield.

Studies on 2-amino-2-deoxy-D-glucose derivatives : XIV. Comparison of stabilities of O-aminoacyl derivatives of 2-acetamido-2-deoxy-D-glucose toward hydrolysis

Abstract The times of half-reaction of 2-acetamido-1-, -3-, -4-, and -6- O -aminoacyl-2-deoxy- D -glucoses on hydrolysis under acidic conditions were measured. The maximum points were generally observed at pH 1.5–2.0 and resulted from the electrostatic repulsion of the protonated amino group. In a higher pH range, the effect of the nucleophilic character of the amino group predominates over the above effect. Consequently, the order of the stability is 6- O -( L -lysyl) ( 2 )>6- O -glycyl ( 1 )>6- O -( L -α-aspartyl) ( 3 ) at pH 3 > 1 > 2 at pH> ca . 4, and 1 >6- O -( N -benzyloxycarbonylglycyl)( 8 ) at the maximum point. The 2-acetamido group of these compounds showed a similar effect to the neighboring ester linkage: 1- O -( N -benzyloxycarbonylglycyl) ( 9 )> 8 , at pH 1.3–2.5. In relation to the position of the ester linkage, the order of the stability at pH 1.5–2.0 is 1 >1- O -glycyl ( 6 ), 3- O -glycyl ( 5 )>4- O -glycyl ( 4 ). A weak effect of the anomeric hydroxyl group was estimated from the comparison of 3 with the ethyl 6- O -( L -α-aspartyl)derivative ( 7 ).

Branched-chain sugars. Part 14. Synthesis of new branched-chain cyclitols having myo- or scyllo-, and muco-configuration from 3-O-benzyl-5,6-dideoxy-5-C-(1,3-dithian-2-yl)-6-nitro-L-idofuranose and -D-glucofuranose

Michael addition of 2-lithio-1,3-dithian to 3-O-benzyl-5,6-dideoxy-1,2-O-isopropylidene-6-nitro-α-D-xylo-hex- 5-enofuranose (1) gives 3-O-benzyl-5,6-dideoxy-5-C-(1,3-dithian-2-yl)-1,2-O-isopropylidene-6-nitro-β-L-idofuranose (2) and -α-D-glucofuranose (3) in the ratio 4 : 3, respectively. Removal of the isopropylidene group and intramolecular cyclization in weak basic conditions gives branched-chain cyclitols having myo- or scyllo-configuration from (2) and muco-configuration from (3). The mechanism of cyclization is discussed.