著者

浜田 康正 水野 章 大野 友靖 塩入 孝之

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.32, no.9, pp.3683-3685, 1984-09-25 (Released:2008-03-31)

参考文献数

12

被引用文献数

7 11

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Condensation of carboxylic acids with tert-butyl hydroperoxide has been smoothly achieved by the use of diethyl phosphorocyanidate and triethylamine under mild reaction conditions, giving tert-butyl peroxycarboxylates in good yields.

著者

原 修 中尾 一成 棚田 喜久 西尾 東 松原 淳 横川 文明 濱田 康正 塩入 孝之

出版者

天然有機化合物討論会

雑誌

天然有機化合物討論会講演要旨集

巻号頁・発行日

no.32, pp.617-624, 1990-09-25

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Calyculins having high cytotoxicity were isolated from the marine sponge Discordermia calyx in the Gulf of Sagami. Calyculin A (1), the major cytotoxic constituent, has 15 chiral centers, a spiroketal bearing phosphate, an oxazole ring, and a nitrile conjugated with all (E)-tetraene. However, its absolute stereostructure has remained uncovered. Interestingly, calyculin A (1) exhibits antitumor activity against Ehrlich and P-388 leukemia in mice. Its unique complex structure as well as its intriguing biological activity led us to investigate the total synthesis of 1, which will determine the absolute configuration of 1 as well. Retrosynthetic analysis has revealed that 1 would be constructed from four fragments A, B, C, and D, shown in Chart 1. Fragments A and B could be prepared by stereoselective reduction of tetronic acid derivatives 11 and 24, respectively. Fragments C and D were prepared from amino acids utilizing the methodology developed by us earlier.

著者

林 恭子 濱田 康正 塩入 孝之

出版者

天然有機化合物討論会実行委員会

雑誌

天然有機化合物討論会講演要旨集

巻号頁・発行日

vol.33, pp.109-115, 1991

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Dolastatin 10, a potent antineoplastic substance, was isolated from an Indian Ocean sea hare, Dolabella auricularia. The absolute stereostructure of dolastatin 10, four constituents of which are unusual amino acids, was unambiguously determined by its total synthesis to be 1. Since the reported synthesis lacks stereo-selectivity, we have developed a more efficient route to dolastatin 10, a medicinally interesting peptide. Z-(S)-Dolaphenine was prepared by the Hantzsch method using Z-L-Phe-NH_2 as a starting material. (2R, 3R, 4S)-Dolaproine was prepared from Boc-(S)-prolinal (5) and N-propionyloxazolidinone 4 by the Evans aldol methodology. The unexpected threo aldol adduct 7 was produced as the major product with a small amount of the expected erythro adduct 6 when di-n-butylboron triflate was used in excess (Table 1). Stereochemistries of these aldol adducts were determined on the basis of ^1H-NMR analyses of their corresponding cyclic derivatives 18. Further investigation about this reversal of selectivity was carried out with a variety of aldehydes including amino aldehydes under the above reaction conditions (Table 2). (3R, 4S, 5S)-Dolaisoleuine, an isostatine analogue, was prepared from Boc-L-isoleucine via the β-ketoester 22, and (S)-dolavaline was prepared from L-valine according to the literature. Assembling each constituent obtained above was efficiently carried out in a stepwise manner from the C-terminal. DEPC was mainly used for the coupling, and the attachment of Boc-L-valine with the tripeptide fragment was accomplished by use of Bop-Cl. Dolastatin 10 (1) thus synthesized was identical with the natural one in every respect.

著者

林 恭子 濱田 康正 塩入 孝之

出版者

天然有機化合物討論会実行委員会

雑誌

天然有機化合物討論会講演要旨集

巻号頁・発行日

vol.33, pp.109-115, 1991

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Dolastatin 10, a potent antineoplastic substance, was isolated from an Indian Ocean sea hare, Dolabella auricularia. The absolute stereostructure of dolastatin 10, four constituents of which are unusual amino acids, was unambiguously determined by its total synthesis to be 1. Since the reported synthesis lacks stereo-selectivity, we have developed a more efficient route to dolastatin 10, a medicinally interesting peptide. Z-(S)-Dolaphenine was prepared by the Hantzsch method using Z-L-Phe-NH_2 as a starting material. (2R, 3R, 4S)-Dolaproine was prepared from Boc-(S)-prolinal (5) and N-propionyloxazolidinone 4 by the Evans aldol methodology. The unexpected threo aldol adduct 7 was produced as the major product with a small amount of the expected erythro adduct 6 when di-n-butylboron triflate was used in excess (Table 1). Stereochemistries of these aldol adducts were determined on the basis of ^1H-NMR analyses of their corresponding cyclic derivatives 18. Further investigation about this reversal of selectivity was carried out with a variety of aldehydes including amino aldehydes under the above reaction conditions (Table 2). (3R, 4S, 5S)-Dolaisoleuine, an isostatine analogue, was prepared from Boc-L-isoleucine via the β-ketoester 22, and (S)-dolavaline was prepared from L-valine according to the literature. Assembling each constituent obtained above was efficiently carried out in a stepwise manner from the C-terminal. DEPC was mainly used for the coupling, and the attachment of Boc-L-valine with the tripeptide fragment was accomplished by use of Bop-Cl. Dolastatin 10 (1) thus synthesized was identical with the natural one in every respect.

著者

横川 文明 塩入 孝之

出版者

The Society of Synthetic Organic Chemistry, Japan

雑誌

有機合成化学協会誌 (ISSN:00379980)

巻号頁・発行日

vol.58, no.7, pp.634-641, 2000-07-01

被引用文献数

4

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Antillatoxin is an ichthyotoxic cyclic lipopeptide isolated by Gerwick and co-workers from the marine cyanobacterium <I>Lyngbya majuscula</I> collected in Curacao. Although we have finished the stereoselective total synthesis of antillatoxin having the proposed structure with (4<I>S</I>, 5<I>R</I>) -configuration, we have found that the synthetic sample was not identical with the natural one and the proposed structure should be revised. Further our synthetic efforts have culminated in the first total synthesis of antillatoxin in its natural form, proving that the natural one has (4<I>R</I>, 5<I>R</I>) -configuration. In this account, our total synthesis and synthetic studies by other groups will be discussed.

著者

青山 豊彦 塩入 孝之

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.115, no.6, pp.446-459, 1995-06-25 (Released:2008-05-30)

参考文献数

22

被引用文献数

3 5

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Tilivalline (1a), a metabolite isolated from Klebsiella pneumoniae var. oxytoca, belongs to a group of pyrrolo [2, 1-c] [1, 4] benzodiazepines, a characteristic skeleton of anthramycin-type antitumor antibiotics. We have accomplished a completely stereoselective, efficient and convenient synthesis of 1a utilizing a new Mannich type intramolecular cyclization as a key step. Further, a computational chemical analysis clarified the effect of zinc chloride on the high stereoselectivity in the tilivalline synthesis. To aim both the extension of the scope of the new Mannich type intramolecular cyclization and the studies on the structure-biological activity relationship, we further extended the method to the synthesis of tilivalline derivatives and 2-(3'-indolyl)-1, 4-benzodiazepines (50). Investigation on the cytotoxicity of 1a and its analogs has revealed that 1a shows the strong cytotoxicity toward mouse leukemia L 1210 cells and the replacement of the indole function of 1a with cyano one increases the cytotoxicity of 1a about 100 times (IC50=0.05 μg/ml).

著者

塩入 孝之

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.113, no.11, pp.760-780, 1993-11-25 (Released:2008-05-30)

参考文献数

69

被引用文献数

1

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Recent studies on the new methods and new reagents in organic synthesis developed by our laboratories have been reviewed. Their application to the synthesis of biologically intriguing natural products has been also described. Dolastatin 10 (1), a potent antitumor peptide of marine origin, has been efficiently synthesized by use of diethyl phosphorocyanidate (DEPC), diphenyl phosphorazidate (DPPA) and (+)-2-hydroxy-3-pinanone ((+)-HyPN). Mugineic acid (27), a typical phytosiderophore from barley, has been synthesized using a phenyl group as a carboxyl synthon. The method is quite efficient to produce mugineic acid on a large scale. Tilivalline (50), isolated from Klebsiella pneumoniae var. oxytoca, has been synthesized by use of DPPA as an +NH2 synthon and DEPC as a coupling reagent. The new Mannich type reaction has been explored to construct the pyrrolo [2.1-c] [1.4] benzodiazepine skeleton. The chiral phase transfer catalyst (65a) based on cinchonine has been utilized for the asymmetric hydroxylation of the α-tetralone derivatives (63). The first synthesis of the chiral ammonium fluoride (71) has been achieved, and its use for the silicon-based asymmetric aldol reaction has been accomplished. Trimethylsilyldiazomethane (TMSCHN2) has been developed as a stable and safe substitute for hazardous diazomethane. As a C1-unit introducing reagent, TMSCHN2 and its lithium salt mostly realize the reactions similar to those carried out with diazomethane. On the other hand, they generally behave as a [C-N-N] azole synthon in an analogous but not as the same way as diazomethane. Using the lithium salt of TMSCHN2, new methods for the preparation of alkynes and pyrroles have been developed.

著者

青山 豊彦 塩入 孝之

出版者

公益社団法人日本薬学会

雑誌

藥學雜誌 = Journal of the Pharmaceutical Society of Japan (ISSN:00316903)

巻号頁・発行日

vol.115, no.6, pp.446-459, 1995-06-25

参考文献数

22

被引用文献数

5

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Tilivalline (1a), a metabolite isolated from Klebsiella pneumoniae var. oxytoca, belongs to a group of pyrrolo [2, 1-c] [1, 4] benzodiazepines, a characteristic skeleton of anthramycin-type antitumor antibiotics. We have accomplished a completely stereoselective, efficient and convenient synthesis of 1a utilizing a new Mannich type intramolecular cyclization as a key step. Further, a computational chemical analysis clarified the effect of zinc chloride on the high stereoselectivity in the tilivalline synthesis. To aim both the extension of the scope of the new Mannich type intramolecular cyclization and the studies on the structure-biological activity relationship, we further extended the method to the synthesis of tilivalline derivatives and 2-(3'-indolyl)-1, 4-benzodiazepines (50). Investigation on the cytotoxicity of 1a and its analogs has revealed that 1a shows the strong cytotoxicity toward mouse leukemia L 1210 cells and the replacement of the indole function of 1a with cyano one increases the cytotoxicity of 1a about 100 times (IC<SUB>50</SUB>=0.05 &mu;g/ml).

著者

横川 文明 塩入 孝之

出版者

社団法人 有機合成化学協会

雑誌

有機合成化学協会誌 (ISSN:00379980)

巻号頁・発行日

vol.58, no.7, pp.634-641, 2000-07-01 (Released:2009-11-13)

参考文献数

29

被引用文献数

2 4

---

Antillatoxin is an ichthyotoxic cyclic lipopeptide isolated by Gerwick and co-workers from the marine cyanobacterium Lyngbya majuscula collected in Curacao. Although we have finished the stereoselective total synthesis of antillatoxin having the proposed structure with (4S, 5R) -configuration, we have found that the synthetic sample was not identical with the natural one and the proposed structure should be revised. Further our synthetic efforts have culminated in the first total synthesis of antillatoxin in its natural form, proving that the natural one has (4R, 5R) -configuration. In this account, our total synthesis and synthetic studies by other groups will be discussed.

著者

張 功幸 塩入 孝之 青山 豊彦

出版者

社団法人 有機合成化学協会

雑誌

有機合成化学協会誌 (ISSN:00379980)

巻号頁・発行日

vol.67, no.4, pp.357-368, 2009 (Released:2011-04-11)

被引用文献数

1 8

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This review describes the recent application of trimethylsilyldiazomethane (Me3SiCHN2, TMSCHN2), its lithium and magnesium bromide salts [TMSC(Li)N2 and TMSC(MgBr)N2] to the synthesis of heterocycles. Reaction of TMSCHN2 with acyl isocyanates followed by Diels-Alder reaction with propiolates or N-phenylmaleimide affords furans or bicyclic pyridones in a one-pot process, respectively. In addition, TMSCHN2 is useful for the preparation of 2-azaazulenes, aziridines and indolizines. Meanwhile, TMSC(Li)N2 reacts with benzynes generated from halobenzenes to yield 3-trimethylsilylindazoles, which are easily converted to 1-arylindazoles or indazoles bearing 3-hydroxymethyl units. TMSC(Li)N2 is also applicable to the synthesis of indoles, benzofurans, pyrroles, thiophenes and 2,3-benzodiazepines. By using TMSC(MgBr)N2, α-substituted β-trimethylsilyl-α,β-epoxyesters can be synthesized from α-ketoesters in a one-pot process. Reaction of TMSC(MgBr)N2 with carbonyl compounds efficiently furnishes trimethylsilylated diazoalcohols, which react with propiolates to give di- or tri-substituted pyrazoles.