Toshitsugu Kai

Convenient synthesis of 7' and 6'-bromo-D-tryptophan and their derivatives by enzymatic optical resolution using D-aminoacylase

Abstract Compounds 7′ and 6′-bromo- d -tryptophan ( 1 and 2 ) which are important derivatives for the synthesis of the chloropeptin and kistamycin A, respectively, were conveniently synthesized by optical resolution from N-acetyl-7′ and 6′-bromo- dl -tryptophan ((RS)-5 and (RS)-14 ) using d -aminoacylase.

Macrocyclization by TTN oxidation for the synthesis of chloropeptin left-hand segment

Abstract Cyclic tripeptides containing a diphenylether bond of the Chloropeptin left-hand segment were synthesized with the use of TTN phenolic oxidation in high yield. They were found to exist as equilibrium mixtures of two stable conformers caused by a rotation of the amide bond in solution.

Novel practical synthesis of Kdn2en and its C-4 nitrogen-modified derivatives

A practical synthesis of Kdn2en and 4-amino-4-deoxy-Kdn2en has been achieved via a key intermediate, methyl 4,5,7,8,9-penta-O-acetyl-2,6-anhydro-3-deoxy-D-glycero-D-galacto-non-2- enonate, which has been prepared from Kdn in three steps in 91% overall yield.

Syntheses of sialic acid analogues with acylamino groups at C-4 (N-acyl regioisomers of sialic acids)

Abstract Methyl 5,7,8,9- tetra -O- acetyl-4-acylamino-2,6-anhydro-3,4-dideoxy- d -glycero- d -galacto - and d - talo -non-2-enonates were synthesized from the reaction of the peracetate of Kdn methyl ester with several nitriles in the presence of a Lewis acid. Treatment of these 2,4-dideoxy-4-acylamino-Kdn methyl esters with N -bromosuccinimide in methanol gave methyl (methyl 5,7,8,9-tetra -O- acetyl-4-acylamino-3-bromo-3,4-dideoxy- d -erythro-α- l -manno- non-2-ulopyranosid)onates ( 16, 18 , and 20 ) and oxazine-type derivatives, 2-alkyl-(methyl 5,7,8,9-tetra -O- acetyl-3-bromo-3,4-dideoxy- d -erythro-α- l -manno- non-2-ulopyranosonate)-5,6-dihydro -4H-1.3- oxazine ( 29, 30 , and 31 ). Debromination of 16, 18 , and 20 with Bu 3 SnH/AIBN in toluene gave methyl (methyl 5,7,8,9-tetra -O- acetyl-4-acylamino-3,4-dideoxy-β- d -glycero- d -galacto- nonulopyranosid)onate ( 23, 24 , and 25 ), whereas hydrolysis with HOAc and subsequent debromination with Bu 3 SnH/AIBN in toluene of 32 and 33 gave methyl 5,7,8,9- tetra -O- acetyl-4-acylamino-3,4-dideoxy-β- d -glycero- d -talo-2- nonulopyranosonate ( 35 and 36 ) in the final step of the synthesis.

Synthesis of Sialic Acid Analogues with the Oxime Group at C-4 Or C-5 of KDN 1

Abstract The readily available methyl (methyl 3-deoxy-5,8:7,9-di-O-isopropylidene-β-D-glycero-D-galacto-2-nonulopyranosid)onate (7) was converted in five synthetic steps into methyl (methyl 4-acetamido-3,4-dideoxy-β-D-glycero-D-talo-2-nonulopyranosid)onate (11). Selective protection of the C-4, C-7, C-8 and C-9 hydroxy groups of methyl (methyl 3-deoxy-8,9-O-isopropylidene-β-D-glycero-D-galacto-2-nonulpyranosid)onate (2) followed by oxidation of the C-5 hydroxy group and then its oximination gave 5-hydroxyimino derivatives (15 and 16). 1. Presented at the XVIIIth International Carbohydrate Symposium, Milan, Italy, July 21-26, 1996.

Novel benzoyl migration of the intermediary 1:1 adducts of 1,3-dipolar cycloaddition of thiazolo[3,2-b][1,2,4]-triazolium N-phenacylides with dimethyl acetylenedicarboxylate

Abstract Reaction of thiazolo[3,2- b ][1,2,4]triazolium N -phenacylides 3 with dimethyl acetylene-dicarboxylate gave novel compounds, 2-(1 H -pyrrolo[2,1- c ]-1,2,4-triazolyl)ethenyl thiobenzoates 4 and 2-[2-(1 H -pyrrolo[2,1- c ]-1,2,4-triazolyl)ethenylthio]propenoates 5 . The former products 4 would be formed via a new type of intramolecular benzoyl migration of the intermediary 1:1 adducts 6 .

Synthesis of 4-Oxo and 4-Hydroxyimino-4-Deoxy-Kdn2En Derivatives

ABSTRACT 2,6-Anhydro-3-deoxy-D-manno-non-2-en-4-ulosonic acid (4-oxo-Kdn2en, 2) was synthesized from methyl 2,6-anhydro-3-deoxy-D-glycero-D-galacto-non-2-enonate (Kdn-2en methyl ester, 7) by the oxidation with manganese dioxide in dry acetone in good yield. 4-Hydroxyimino-Kdn2en derivatives (3), and 4-carbethoxymethylene-Kdn2en derivatives (4) were synthesized from the peracetylated methyl ester of 4-oxo-Kdn2en by oximation and Wittig reaction in good yield, respectively.

OXIDATION PRODUCTS OF C-4 AND C-7 HYDROXYLS IN THE METHYL ALPHA -GLYCOSIDEDERIVATIVES OF KDN

Abstract A regioselective protection of hydroxyl groups in the methyl ester-methyl α-glycoside derivative of KDN was demonstrated. Isopropylidenation of methyl (methyl 3-deoxy-α-D-glycero-D-galacto-2-nonulopyranosid)onate (1) gave mono- (8,9) and di- (5,7:8,9) O-isopropylidene derivatives. Benzoylation of methyl (methyl 3-deoxy-8, 9-O-isopropylidene-α-D-glycero-D-galacto-2-nonulopyranosid)onate (7) gave di- (4,5) and tri- (4,5,7) O-benzoates. Through these reactions, it was found that the reactivity of the hydroxyl groups was different from that of methyl β-glycoside of KDN. Oxidation products of C-4 and C-7 hydroxyl groups (6 and 11) were synthesized from these compounds. 1. Presented at the XVIIIth International Carbohydrate Symposium, Milan, Italy, July 21-26, 1996.