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【结 构 式】 
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【分子编号】10899 【品名】tert-butyl 2-[(2R,6S)-6-[[(benzyloxy)carbonyl]amino]-7-[[(1R)-2-(benzyloxy)-1-methyl-2-oxoethyl]amino]-2-[(tert-butoxycarbonyl)amino]-7-oxoheptanoyl]-1-hydrazinecarboxylate 【CA登记号】 |
【 分 子 式 】C35H49N5O10 【 分 子 量 】699.80176 【元素组成】C 60.07% H 7.06% N 10.01% O 22.86% |
合成路线1
该中间体在本合成路线中的序号：(IX)1) The cyclization of meso-2,6-bis(benzyloxycarbonylamino)heptanedioic acid (I) with PCl5 gives the corresponding bis oxazolidinedione (II), which is treated with tert-butyl carbazate (III) yielding the bis hydrazide (IV). Enzymatic hydrolysis of (IV) with Streptomyces sapporonensis affords the (S)-monoacid (V), which is selectively protected with benzyl chloroformate and copper chelate (VI). A second protection reaction of (VI) with tert-butoxycarbonyl anhydride gives the amino protected acid (VII) , which is condensed with D-alanine benzyl ester (VIII) by means of isobutyl chloroformate to afford the acylated D-alanine (IX). Elimination of the benzyloxycarbonyl groups of (IX) by hydrogenolysis yields compound (X) with a free amino group, which is condensed with N-heptanoyl-D-glutamic acid 1-benzyl monoester (XI) to give the protected FK-565 precursor (XII). Finally, this compound is deprotected with trifluoroacetic acid and sodium periodate.
| 【1】 Takeno, H.; Kitaura, Y.; Hashimoto, M.; Hemmi, K.; Nakaguchi, O.; Okada, S.; 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, 23, 7026-8. |
| 【2】 Hoshi, A.; Castaner, J.; FK-565. Drugs Fut 1994, 19, 3, 243. |
| 【3】 Hashimoto, M.; Hemmi, K.; Aratani, M.; Nakaguchi, O.; Kitaura, Y.; Yonishi, S.; Okada, S.; Takeno, H.; Synthesis and RES-stimulating activity of bacterial cell-wall peptidoglycan peptides related to FK-156. Experientia 1982, 38, 1101-3. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 10130 | (2R,6S)-2,6-Bis[[(benzyloxy)carbonyl]amino]heptanedioic acid | C23H26N2O8 | 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 | |
| (III) | 10893 | tert-butyl 1-hydrazinecarboxylate; tert-butyl carbazate | 870-46-2 | C5H12N2O2 | 详情 | 详情 |
| (IV) | 10894 | tert-butyl 2-[(2R,6S)-2,6-diamino-7-[2-(tert-butoxycarbonyl)hydrazino]-7-oxoheptanoyl]-1-hydrazinecarboxylate | C17H34N6O6 | 详情 | 详情 | |
| (V) | 10895 | (2S,6R)-2,6-Diamino-7-[2-(tert-butoxycarbonyl)hydrazino]-7-oxoheptanoic acid | C12H24N4O5 | 详情 | 详情 | |
| (VI) | 10896 | (2S,6R)-6-Amino-2-[[(benzyloxy)carbonyl]amino]-7-[2-(tert-butoxycarbonyl)hydrazino]-7-oxoheptanoic acid | C20H30N4O7 | 详情 | 详情 | |
| (VII) | 10897 | (2S,6R)-2-[[(Benzyloxy)carbonyl]amino]-6-[(tert-butoxycarbonyl)amino]-7-[2-(tert-butoxycarbonyl)hydrazino]-7-oxoheptanoic acid | C25H38N4O9 | 详情 | 详情 | |
| (VIII) | 10898 | benzyl (2R)-2-aminopropanoate | C10H13NO2 | 详情 | 详情 | |
| (IX) | 10899 | tert-butyl 2-[(2R,6S)-6-[[(benzyloxy)carbonyl]amino]-7-[[(1R)-2-(benzyloxy)-1-methyl-2-oxoethyl]amino]-2-[(tert-butoxycarbonyl)amino]-7-oxoheptanoyl]-1-hydrazinecarboxylate | C35H49N5O10 | 详情 | 详情 | |
| (X) | 10900 | (2R)-2-([(2S,6R)-2-Amino-6-[(tert-butoxycarbonyl)amino]-7-[2-(tert-butoxycarbonyl)hydrazino]-7-oxoheptanoyl]amino)propionic acid | C20H37N5O8 | 详情 | 详情 | |
| (XI) | 10901 | (4R)-5-(Benzyloxy)-4-(heptanoylamino)-5-oxopentanoic acid | C19H27NO5 | 详情 | 详情 | |
| (XII) | 10902 | (2R)-2-([(2S,6R)-2-[[(4R)-5-(Benzyloxy)-4-(heptanoylamino)-5-oxopentanoyl]amino]-6-[(tert-butoxycarbonyl)amino]-7-[2-(tert-butoxycarbonyl)hydrazino]-7-oxoheptanoyl]amino)propionic acid | C39H62N6O12 | 详情 | 详情 |