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【结 构 式】

【分子编号】36116

【品名】(4R,7S,10R,15S)-15-[(4R)-4-amino-5-hydrazino-5-oxopentyl]-10-carboxy-4,7-dimethyl-2,5,8,13,16-pentaoxo-3-oxa-6,9,14,17-tetraazanonadecan-19-oic acid

【CA登记号】

【 分 子 式 】C22H37N7O11

【 分 子 量 】575.57636

【元素组成】C 45.91% H 6.48% N 17.03% O 30.58%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(XXIX)

The reaction of the dianhydride (II) with benzyl carbazate (E) gives the bis(benzyloxycarbonylhydrazide) compound (XXI), which by an enzymatic treatment with an aminopeptidase from Streptomyces sapporonensis yields the monohydrazide (XXII). The protection of (XXII) with benzyloxycarbonyl chloride (B) affords the protected monohydrazide (XXIII), which is cyclized by treatment with SOCl2 giving the monocarboxy anhydride (XXIV). Hydrolysis of (XXIV) with HCl yields amino acid (XXV), which is condensed with glycine (XXVI) to afford the dipeptide (XXVII). The condensation of (XXVII) with (X) gives the protected FK-156 (XXVIII), which is debenzylated by hydrogenolysis with H2 over Pd/C in methanol-acetic acid affording FK-156 still protected with an acetoxy and a hydrazine group (XXIX).

1 Hemmi, K.; Nakaguchi, O.; Hashimoto, M.; Taleno, H.; Kitaura, Y.; Okada, S.; An efficient method for selective amino acid protection of meso-2,2'-diaminocarboxylic acid: An improved synthesis of FK-156. Tetrahedron Lett 1982, 23, 6, 693-696.
2 Imanaka, H.; Nakahaa, K.; Gotoh, T.; Aoki, H.; Iwami, M.; Studies on a new immunoactive peptide, FK-156. I. Taxonomy of the producing strains. J Antibiot 1982, 35, 10, 1280-85.
3 Okada, S.; Hemmi, K.; Takano, H.; Hashimoto, M.; Nakaguchi, O.; Kitaura, Y.; Aratani, M.; Miyazaki, Y.; Studies of a new immunoactive peptide, FK-156. IV. Synthesis od FK-156 and its geometric isomer. J Antibiot 1982, 35, 10, 1300-11.
4 Gotoh, T.; Imoraka, H.; Nakahara, K.; Tanaka, H.; Uchida, I.; Kawai, Y.; Studies on a new immunoactive peptide, FK-156. III. Structure elucidation. J Antibiot 1982, 35, 10, 1293-99.
5 Okahara, M.; Nakahara, K.; Gotoh, T.; Hashimoto, M..; Kino, T.; Aoki, H.; Imanaka, H.; Kohsaka, M.; Nishiura, T.; Kuroda, Y.; Studies on a new immunoactive peptide, FK-156. II. Fermentation, extraction and chemical and biological charaterization. J Antibiot 1982, 35, 10, 1286-92.
6 Kitaura, Y.; Nakaguchi, O.; Hemmi, K.; Aratani, M.; Takeno, H.; Okada, S.; Tanaka, H.; Hashimoto, M. (Fujisawa Pharmaceutical Co., Ltd.); New peptides, processes for their preparation and pharmaceutical compsns. containing them. EP 0027260 .
7 Kitaura, Y.; Nakaguchi, O.; Hemmi, K. (Fujisawa Pharmaceutical Co., Ltd.); New lactyl tetrapeptide, processes for preparation thereof and pharmaceutical compsns. containing it. EP 0011283 .
8 Arya, V.P.; Blancafort, P.; Castaner, J.; Serradell, M.N.; FK-156. Drugs Fut 1983, 8, 8, 667.
9 Hemmi, K.; Takeno, H.; Okada, S.; Nakaguchi, O.; Kitaura, Y.; Hashimoto, M.; Total synthesis of FK-156 isolated from a Streptomyces as an immunostimulating peptide: Application of a novel copper chelate amino protection. J Am Chem Soc 1981, 103, 7026.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(B) 10101 Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene 501-53-1 C8H7ClO2 详情 详情
(E) 36108 benzyl 1-hydrazinecarboxylate 5331-43-1 C8H10N2O2 详情 详情
(II) 10892 (4R)-4-[3-[(4S)-2,5-Dioxo-1,3-oxazolan-4-yl]propyl]-1,3-oxazolane-2,5-dione C9H10N2O6 详情 详情
(X) 36102 (4R)-4-[((2S)-2-[[(2R)-2-(acetoxy)propanoyl]amino]propanoyl)amino]-5-(benzyloxy)-5-oxopentanoic acid C20H26N2O8 详情 详情
(XXI) 36109 benzyl 2-((2R,6S)-2,6-diamino-7-[2-[(benzyloxy)carbonyl]hydrazino]-7-oxoheptanoyl)-1-hydrazinecarboxylate C23H30N6O6 详情 详情
(XXII) 36110 (2S,6R)-2,6-diamino-7-[2-[(benzyloxy)carbonyl]hydrazino]-7-oxoheptanoic acid C15H22N4O5 详情 详情
(XXIII) 36111 (2S,6R)-2,6-bis[[(benzyloxy)carbonyl]amino]-7-[2-[(benzyloxy)carbonyl]hydrazino]-7-oxoheptanoic acid C31H34N4O9 详情 详情
(XXIV) 36112 benzyl 2-[(2R)-2-[[(benzyloxy)carbonyl]amino]-5-[(4S)-2,5-dioxo-1,3-oxazolidin-4-yl]pentanoyl]-1-hydrazinecarboxylate C24H26N4O8 详情 详情
(XXV) 36113 (2S,6R)-2-amino-6-[[(benzyloxy)carbonyl]amino]-7-[2-[(benzyloxy)carbonyl]hydrazino]-7-oxoheptanoic acid C23H28N4O7 详情 详情
(XXVI) 20436 glycine 56-40-6 C2H5NO2 详情 详情
(XXVII) 36114 2-[((2S,6R)-2-amino-6-[[(benzyloxy)carbonyl]amino]-7-[2-[(benzyloxy)carbonyl]hydrazino]-7-oxoheptanoyl)amino]acetic acid C25H31N5O8 详情 详情
(XXVIII) 36115 (4R,7S,10R,15S)-10-[(benzyloxy)carbonyl]-15-((4R)-4-[[(benzyloxy)carbonyl]amino]-5-[2-[(benzyloxy)carbonyl]hydrazino]-5-oxopentyl)-4,7-dimethyl-2,5,8,13,16-pentaoxo-3-oxa-6,9,14,17-tetraazanonadecan-19-oic acid C45H55N7O15 详情 详情
(XXIX) 36116 (4R,7S,10R,15S)-15-[(4R)-4-amino-5-hydrazino-5-oxopentyl]-10-carboxy-4,7-dimethyl-2,5,8,13,16-pentaoxo-3-oxa-6,9,14,17-tetraazanonadecan-19-oic acid C22H37N7O11 详情 详情

合成路线2

该中间体在本合成路线中的序号:(XXIX)

The reaction of (XXIX) with Br2 eliminates the hydrazino group giving acetyl-FK-156 (XXX), which is finally treated with Na2CO3 to eliminate the acetate group.

1 Hemmi, K.; Nakaguchi, O.; Hashimoto, M.; Taleno, H.; Kitaura, Y.; Okada, S.; An efficient method for selective amino acid protection of meso-2,2'-diaminocarboxylic acid: An improved synthesis of FK-156. Tetrahedron Lett 1982, 23, 6, 693-696.
2 Gotoh, T.; Imoraka, H.; Nakahara, K.; Tanaka, H.; Uchida, I.; Kawai, Y.; Studies on a new immunoactive peptide, FK-156. III. Structure elucidation. J Antibiot 1982, 35, 10, 1293-99.
3 Imanaka, H.; Nakahaa, K.; Gotoh, T.; Aoki, H.; Iwami, M.; Studies on a new immunoactive peptide, FK-156. I. Taxonomy of the producing strains. J Antibiot 1982, 35, 10, 1280-85.
4 Okada, S.; Hemmi, K.; Takano, H.; Hashimoto, M.; Nakaguchi, O.; Kitaura, Y.; Aratani, M.; Miyazaki, Y.; Studies of a new immunoactive peptide, FK-156. IV. Synthesis od FK-156 and its geometric isomer. J Antibiot 1982, 35, 10, 1300-11.
5 Okahara, M.; Nakahara, K.; Gotoh, T.; Hashimoto, M..; Kino, T.; Aoki, H.; Imanaka, H.; Kohsaka, M.; Nishiura, T.; Kuroda, Y.; Studies on a new immunoactive peptide, FK-156. II. Fermentation, extraction and chemical and biological charaterization. J Antibiot 1982, 35, 10, 1286-92.
6 Kitaura, Y.; Nakaguchi, O.; Hemmi, K. (Fujisawa Pharmaceutical Co., Ltd.); New lactyl tetrapeptide, processes for preparation thereof and pharmaceutical compsns. containing it. EP 0011283 .
7 Kitaura, Y.; Nakaguchi, O.; Hemmi, K.; Aratani, M.; Takeno, H.; Okada, S.; Tanaka, H.; Hashimoto, M. (Fujisawa Pharmaceutical Co., Ltd.); New peptides, processes for their preparation and pharmaceutical compsns. containing them. EP 0027260 .
8 Arya, V.P.; Blancafort, P.; Castaner, J.; Serradell, M.N.; FK-156. Drugs Fut 1983, 8, 8, 667.
9 Hemmi, K.; Takeno, H.; Okada, S.; Nakaguchi, O.; Kitaura, Y.; Hashimoto, M.; Total synthesis of FK-156 isolated from a Streptomyces as an immunostimulating peptide: Application of a novel copper chelate amino protection. J Am Chem Soc 1981, 103, 7026.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XXIX) 36116 (4R,7S,10R,15S)-15-[(4R)-4-amino-5-hydrazino-5-oxopentyl]-10-carboxy-4,7-dimethyl-2,5,8,13,16-pentaoxo-3-oxa-6,9,14,17-tetraazanonadecan-19-oic acid C22H37N7O11 详情 详情
(XXX) 36117 (4R,7S,10R,15S)-15-[(4R)-4-amino-4-carboxybutyl]-10-carboxy-4,7-dimethyl-2,5,8,13,16-pentaoxo-3-oxa-6,9,14,17-tetraazanonadecan-19-oic acid C22H35N5O12 详情 详情
Extended Information