Kimio Takahashi

A Convenient Synthesis of 1H-1,2,4-Triazol-1-Yl-Propan-3-One Derivatives by Modified Mannich Reaction

Abstract 1H-1,2,4-Triazol-1-yl-propan-3-ones were synthesized regioselectively using a modified Mannich reaction. Reactions of enones and Mannich bases with imidazole are also described.

Synthesis of a prostaglandin endoperoxide model compound and its reaction with electron transfer reagents

Abstract 5-Exo-phenyl-2,3-dioxabicyclo[2.2.1]heptane (4c) was synthesized as a model compound of prostaglandin endoperoxide (PGH) to mimic the bioconversion of PGH into thromboxane (TX). The reaction of (4c) with various electron transfer reagents was investigated. With the aid of a catalytic amount of ferrous ion, (4c) was successfully converted into the thromboxane B (TXB) skeleton.

Electrophile-initiated conversion of a prostaglandin endoperoxide model compound to the thromboxane B skeleton

Abstract Reaction of the simplified prostaglandin endoperoxide model (1) with ferric or cupric ion afforded the lactols ( 2a , b ) containing the thromboxane B ring moiety, along with ketol ( 3 ) and levulinaldehyde derivatives ( 4, 5 ).

Synthesis of 2,3-dihydro-1H-pyrrolo[1,2-a]indoles by intramolecular nucleophilic aromatic substitution

Condensation of 2-methoxy-Δ1-pyrroline (3) with 2-bromo-5-methoxy-4-methylphenylacetonitrile (6)[prepared from 3-hydroxy-4-methylbenzaldehyde (17) in four steps] gave α-(2-bromo-5-methoxy-4-methylphenyl)-α-pyrrolidin-2-ylideneacetonitrile (10). Several other α-aryl-α-pyrrolidin-2-ylideneacetonitriles [(8), (9), and (11)] were also synthesised from the corresponding phenylacetonitriles [(4), (5), and (7)]. (Z)-α-Aryl-α-pyrrolidin-2-ylideneacetates [(14)–(16)] were prepared by similar condensation reactions or by ethanolysis of the nitriles (8) and (10). Treatment of compounds (9), (10), and (16) with sodium hydride and copper(I) bromide in dimethylformamide gave quantitatively the 2,3-dihydro-1H-pyrrolo[1,2-a]indole-9-carbonitriles (21)–(23). Heating the nitriles (21) and (22) with nickel–aluminium alloy in aqueous acetic acid yielded the corresponding aldehydes (24) and (25). 2,3-Dihydro-7-methoxy-6-methyl-1H-pyrrolo[1,2-a]indole-9-carbaldehyde (25) was further converted via the 8-nitro-compound (26) into the 5,8-quinone (28).

Studies on the syntheses of heterocyclic compounds. Part 777. A synthetic approach to seco-mitosane type of compound related to mitomycins

1,2,3,4,5 6-Hexahydro-5,5,8-trimethoxy-9-methyl-1-benzazocine-7,10-dione (1b) has been synthesised from 2,3-dihydro-7-methoxy-6-methyl-1H-pyrrolo[1,2-a]indole-5.8-dione (10c). The key intermediate, 7,10-diacetoxy-5-trifluoroacetoxy-1-trifluoroacetyl-1,2,3,4,5,6-hexahydro-8-methoxy-9-methyl-1-benzazocine (13b), was prepared by a ring-opening reaction of 5,8-diacetoxy-1,2,9,9a-tetrahydro-7-methoxy-6-methyl-1H-pyrrolo-[1,2-a]indole (12) with trifluoroacetic anhydride. An alternative route to 1,2,3,4,5,6-hexahydro-1-benzazocine (7d) from 2,3,9,9a-hexahydro-7-methoxy-6-methyl-1H-pyrrolo[1,2-a]indole (6) has also been devised.

Studies on the syntheses of heterocyclic compounds. Part 744. A synthesis of 1-benzazocin-5-ones from 2,3-dihydro-1H-pyrrolo[1,2-a]indoles; a synthetic approach to the mitomycins

On reduction with sodium borohydride in acetic acid, the 2,3-dihydro-1H-pyrrolo[1,2-a]indoles (4) and (5) were converted into the indolines (6) and (7), which were treated with cyanogen bromide to give selectively the 5-bromo-1-cyano-1,2,3,4,5,6-hexahydro-1-benzazocines (10) and (11). The bromides (10) and (11) were transformed into 1-cyano-1,3,4,6-tetrahydro-1-benzazocin-5(2H)-ones (13) and (14), which underwent a transannular reaction to yield the 2,3-dihydro-1H-pyrrolo[1,2-a]indoles (4) and (5).

Studies on the syntheses of heterocyclic compounds. Part 676. Synthesis of 1-substituted 7-methoxymitosenes

On treatment with lead tetra-acetate in acetic acid, the 2,3-dihydro-1H-pyrrolo[1,2-a]indoles (4)–(8) were selectively acetoxylated at C-1 to give the acetates (13)–(17). The acetates (16) and (17) and 1-acetoxy-2,3-dihydro-7-methoxy-6-methyl-5,8-dioxo-1H-pyrrolo[1,2-a]indole-9-carbaldehyde (27) were hydrolysed to the corresponding alcohols (20), (21), and (28). The alcohols (20) and (21) were oxidised to the 1-ketones (22) and (23), and (28) was chlorinated with methanesulphonyl chloride and lithium chloride in dimethylformamide to give 1-chloro-2,3-dihydro-7-methoxy-6-methyl-5,8-dioxo-1H-pyrrolo[1,2-a]indole-9-carbaldehyde(29). On heating the acetates (13), (14), and (17) in acetic acid, elimination of acetic acid occurred to yield the 3H-pyrrolo[1,2-a]indoles (24)–(26).

Studies on the syntheses of heterocyclic compounds. Part DLXXXIX. A simple route to pyridocarbazoles

Die Grignardierung des Pyridins (I) mit dem Reagenz (II) und anschliesende Acetylierung ergeben die isomeren Derivate (III) und (IV), die durch Umsetzung mit 47%igem HBr gefolgt von Acetylierung in die Pyridocarbazole (V) bzw. (VI) ubergefuhrt werden.