Junko Nobuhiro

Publications (10)9.62 Total impact

• Article: The enantioselective total synthesis of a beta-carboline alkaloid, (S)-(-)-dichotomine C.

  Kana Omura, Tominari Choshi, Shiroh Watanabe, Yuhsuke Satoh, Junko Nobuhiro, Satoshi Hibino
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  ABSTRACT: The first enantioselective synthesis of a beta-carboline alkaloid, dichotomine C, possessing antiallergic effects, was achieved by constructing a beta-carboline framework based on the microwave-assisted thermal electrocyclic reaction of a 1-azahexatriene system, followed by the Sharpless asymmetric dihydroxylation.
  CHEMICAL & PHARMACEUTICAL BULLETIN 03/2008; 56(2):237-8. · 1.59 Impact Factor
• Article: Lipase-catalyzed asymmetric synthesis of desprenyl-carquinostatin A and descycloavandulyl-lavanduquinocin.

  Tominari Choshi, Yoshinari Uchida, Yukiko Kubota, Junko Nobuhiro, Mitsuhiro Takeshita, Takushi Hatano, Satoshi Hibino
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  ABSTRACT: An asymmetric synthesis of the core carbazole structure, 6-desprenyl-carquinostatin 3 and 6-descycloavandulyl-lavanduquinocin 3, toward a total synthesis of carquinostatin A (1) and lavanduquinocin (2), has been established. Lipase QLM (Meito) catalyzed enantioselective acetylation of the racemic alcohol 6 gave the (-)-acetate 7 and the (+)-alcohol 6 with high enantioselectivity. The absolute stereochemistry of the (-)- and (+)-alcohol 6 have been determined to be R- and S-configurations, respectively, by the advanced Mosher method. In the same manner, the (-)-acetate 13 and the (+)-alcohol 12 have been obtained from the racemic alcohol 12. The (R)-(-)-acetate 13, derived from the (R)-(-)-acetate 7, was the same as the (-)-acetate 13, which has been determined to be (R)-configuration. Oxidation of the (R)-(-)-acetate 13 followed by hydrolysis afforded (R)-(-)-6-desprenyl-carquinostatin [and (R)-(-)-6-descycloavandulyl-lavanduquinocin] 3. In addition, oxidation of the (S)-(+)-alcohol 12 provided (S)-(+)-3, which is the enantiomer of 6-desprenyl-carquinostatin A (R)-(-)-3.
  CHEMICAL & PHARMACEUTICAL BULLETIN 08/2007; 55(7):1060-4. · 1.59 Impact Factor
• Article: Synthesis of 6‐Methylindole‐4,7‐quinone and Antitumor Activities of Its Related Indolequinones.

  Junko Nobuhiro, Maho Hirayama, Tominari Choshi, Keiichi Kamoshita, Sakiko Maruyama, Yoshikazu Sukenaga, Takashi Ishizu, Haruto Fujioka, Satoshi Hibino
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  ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
  ChemInform 05/2007; 38(22).
• Article: Suppression of laser-induced choroidal neovascularization by subconjunctival injection of 9alpha-fluoromedroxyprogesterone acetate (FMPA), an anti-angiogenic agent, in rats.

  Natsuko Murata, Taketo Yamaji, Masayuki Uchida, Hiroshi Tsuboi, Hiroto Suzuki, Masashi Yamada, Tsutomu Oikawa, Junko Nobuhiro, Tominari Choshi, Satoshi Hibino
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  ABSTRACT: 9alpha-Fluoromedroxyprogesterone acetate (FMPA) is a synthetic analog of medroxyprogesterone acetate (MPA). FMPA exhibited more potent anti-tumor and anti-angiogenic activities in some assay systems than the parent agent, MPA. Exudative age-related macular degeneration (AMD) is characterized by choroidal neovascularization (CNV). Anecortave acetate, an angiostatic steroid, is clinically efficacious in patients with exudative AMD. Betamethasone is an anti-angiogenic steroid. Therefore, we examined the effects of FMPA, anecortave acetate and betamethasone on laser-induced CNV in rats. Anecortave acetate and betamethasone were included as positive controls. Crypton laser was applied to the fundus in Brown Norway rats. Laser photocoagulations were performed in each eye between the major retinal vessels of the superior retina. Subconjunctival injection of FMPA, anecortave acetate or betamethasone was performed once just after the photocoagulation (on day 0). The incidence of CNV formation was evaluated by fluorescein angiography (FAG) on day 14. On the next day, examination of the retinal function was performed by electro retinogram (ERG). Subconjunctival injection of FMPA at doses of 300, 1000 and 3000 microg/eye dose-dependently inhibited the incidence of CNV formation. Significant differences were observed at doses of 1000 and 3000 microg/eye of FMPA as compared with the control group. Anecortave acetate and betamethasone significantly inhibited the incidence of CNV formation. FMPA at the doses used in this study did not affect the retinal function in rats, as determined by ERG. FMPA appeared to be effective in a rat model of CNV, so it was demonstrated that FMPA might be useful in the treatment of AMD.
  Biological & Pharmaceutical Bulletin 01/2007; 29(12):2410-4. · 1.66 Impact Factor
• Article: Synthesis and anti-tumor activity of a fluorinated analog of medroxyprogesterone acetate (MPA), 9alpha-fluoromedroxyprogesterone acetate (FMPA).

  Natsuko Murata, Shiho Fujimori, Yoshitatsu Ichihara, Yoshio Sato, Taketo Yamaji, Hiroshi Tsuboi, Masayuki Uchida, Hiroto Suzuki, Masashi Yamada, Tsutomu Oikawa, Hideo Nemoto, Junko Nobuhiro, Tominari Choshi, Satoshi Hibino
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  ABSTRACT: We synthesized 9alpha-fluoromedroxyprogesterone acetate (FMPA) in order to test whether it is a more potent anti-angiogenic agent than medroxyprogesterone acetate (MPA), which has been widely used as a therapeutic agent for breast and endometrium cancers. FMPA was previously synthesized in 10 steps (total yield: 1%). An efficient synthesis of FMPA has been achieved in 6 steps (total yield: 12%). We examined the anti-tumor effect of FMPA, complexed with dimethyl-beta-cyclodextrin (DM-beta-CyD), on rat mammary carcinomas induced by 7,12-dimethylbenz[a]anthracene (DMBA). FMPA showed great anti-tumor effect on DMBA-induced rat mammary carcinomas.
  CHEMICAL & PHARMACEUTICAL BULLETIN 12/2006; 54(11):1567-70. · 1.59 Impact Factor
• Article: Synthesis of the new furo[3,2-h]isoquinoline alkaloid, TMC-120B from Aspergillus ustus.

  Teppei Kumemura, Tominari Choshi, Aki Hirata, Mitsuko Sera, Yohhei Takahashi, Junko Nobuhiro, Satoshi Hibino
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  ABSTRACT: A total synthesis of a new furo[3,2-h]isoquinoline alkaloid TMC120-B (2), isolated from Aspergillus ustus together with two related compounds, has been completed in sixteen steps. The key step is the synthesis of the appropriate 3,7,8-trisubstituted isoquinoline framework (23) based on a thermal electrocyclic reaction of the 1-aza 6pi-electron system involving the benzene double bond. In addition, the microwave assisted electrocyclic reaction of this system was newly performed.
  CHEMICAL & PHARMACEUTICAL BULLETIN 05/2005; 53(4):393-7. · 1.59 Impact Factor
• Article: A Total Synthesis of a New Type of Furo[3,2‐h]isoquinoline Alkaloids, TMC‐120B.

  Teppei Kumemura, Tominari Choshi, Aki Hirata, Mitsuko Sera, Yohhei Takahashi, Junko Nobuhiro, Satoshi Hibino
  ChemInform 04/2004; 35(19).
• Source

  Available from: pharm.or.jp

  Article: The absolute configuration of (+)-oxopropaline D by theoretical calculation of specific rotation and asymmetric synthesis.

  Takeshi Kuwada, Miyako Fukui, Toshiyuki Hata, Tominari Choshi, Junko Nobuhiro, Yukio Ono, Satoshi Hibino
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  ABSTRACT: The specific optical rotations of (R)-oxopropaline D calculated by two ab initio MO methods were +52+/-31 degrees and +61+/-29 degrees, respectively, and (+)-oxopropaline D (3) was presumed to have an R-configuration. On the basis of this theoretical result, the reaction of 1-litio-beta-carboline with (R)-glyceraldehyde acetonide followed by oxidation with MnO(2) gave (R)-oxopropaline D acetonide (4a), which was consistent with the previously synthesized (+)-oxopropaline D acetonide (4) in all respects. From the results of theoretical calculations and the experimental synthesis, we determined that natural (+)-oxopropaline D (3) has an R-configuration.
  CHEMICAL & PHARMACEUTICAL BULLETIN 02/2003; 51(1):20-3. · 1.59 Impact Factor
• Article: Total Syntheses of β-Carboline Alkaloids, (R)-(−)-Pyridindolol K1, (R)-(−)-Pyridindolol K2, and (R)-(−)-Pyridindolol

  Naoko Kanekiyo, Takeshi Kuwada, Tominari Choshi, Junko Nobuhiro, Satoshi Hibino
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  ABSTRACT: The total syntheses of β-carboline alkaloids, (R)-(−)-pyridindolols (1, 5, and 6) are described. The two key steps involved are (1) a thermal electrocyclic reaction of the 3-alkenylindole-2-aldoxime 10 and (2) a thermal cyclization of 3-alkynylindole-2-aldoxime 11 to construct the β-carboline N-oxides 8, which upon heating with acetic anhydride and sequential treatment with trifluoromethanesulfonic anhydride gave the triflates 18. The Stille coupling reaction of 18 with vinylstannane, followed by cleavage of MOM ether, afforded the 1-ethenyl-3-hydroxymethyl-β-carboline (7a). Subsequent acetylation of 7a yielded the acetate 7b, which was subjected to the Sharpless asymmetric 1,2-dihydroxylation by AD-mix-β to produce (R)-(−)-pyridindolol K2 (6). Selective acetylation of 6 was effected by Ac2O and collidine to form (R)-(−)-pyridindolol K1 (5). By contrast, hydrolysis of 6 provided (R)-(−)-pyridindolol (1).
  11/2001;
• Article: Syntheses of the antibiotic alkaloids renierone, mimocin, renierol, renierol acetate, renierol propionate, and 7-methoxy-1,6-dimethylisoquinoline-5,8-dione

  Nagako Kuwabara, Hiroyuki Hayashi, Noriko Hiramatsu, Tominari Choshi, Teppei Kumemura, Junko Nobuhiro, Satoshi Hibino
  Tetrahedron. 60(13):2943-2952.