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【结 构 式】

【分子编号】61904

【品名】6-(tert-butyl) 1-propyl (Z,4S)-4-[(tert-butoxycarbonyl)amino]-2-fluoro-2-hexenedioate

【CA登记号】

【 分 子 式 】C18H30FNO6

【 分 子 量 】375.4377432

【元素组成】C 57.59% H 8.05% F 5.06% N 3.73% O 25.57%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(VII)

The activation of N-Boc-L-aspartic acid 4-O-tert-butyl ester (I) with isopropyl chloroformate (II) in THF gives the mixed anhydride (III), which is reduced with NaBH4 to yield the hydroxyester (IV). The Swern oxidation of (IV) affords the aldehyde (V), which is condensed with the phosphonate (VI) by means of BuLi to provide the hexenedioic diester (VII). The stepwise reduction of (VII) first by means of H2 over Pd/C and then with NaBH4 gives rise to the omega-hydroxy hexanoate (VIII). This is treated first with MsCl and TEA and then with NaN3 to yield a diastereomeric mixture of azido hexanoates (IX) and (X). After separation, the desired isomer (X) is hydrolyzed with LiOH to afford the corresponding carboxylic acid (XI), which is condensed with 2-(1-methylhydrazino)acetic acid tert-butyl ester (XII) by means of HATU and DIEA to provide the corresponding hydrazide (XIII). The reduction of the azido group of (XIII) by means of H2 over Pd/C or with PPh3 in THF/water provides the corresponding amino derivative (XIV), which is finally hydrolyzed and N-deprotected by means of 4M HCl in dioxane to furnish the target fluorinated deoxynegamycin.

1 Raju, B.; Anandan, S.K.; Gu, S.; et al.; Fluorinated deoxynegamycin analogs: Synthesis and antimicrobial properties. 42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002, Abst F-1686.
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) 37623 (2S)-4-(tert-butoxy)-2-[(tert-butoxycarbonyl)amino]-4-oxobutyric acid C13H23NO6 详情 详情
(II) 26492 2-[(chlorocarbonyl)oxy]propane 108-23-6 C4H7ClO2 详情 详情
(III) 61849   C17H29NO8 详情 详情
(IV) 61901 tert-butyl (3S)-3-[(tert-butoxycarbonyl)amino]-4-hydroxybutanoate C13H25NO5 详情 详情
(V) 61902 tert-butyl (3S)-3-[(tert-butoxycarbonyl)amino]-4-oxobutanoate C13H23NO5 详情 详情
(VI) 61903 propyl 2-(dipropoxyphosphoryl)-2-fluoroacetate C11H22FO5P 详情 详情
(VII) 61904 6-(tert-butyl) 1-propyl (Z,4S)-4-[(tert-butoxycarbonyl)amino]-2-fluoro-2-hexenedioate C18H30FNO6 详情 详情
(VIII) 61905 tert-butyl (3S)-3-[(tert-butoxycarbonyl)amino]-5-fluoro-6-hydroxyhexanoate C15H28FNO5 详情 详情
(IX) 61906 tert-butyl (3S,5S)-6-azido-3-[(tert-butoxycarbonyl)amino]-5-fluorohexanoate C15H27FN4O4 详情 详情
(X) 61907 tert-butyl (3S,5R)-6-azido-3-[(tert-butoxycarbonyl)amino]-5-fluorohexanoate C15H27FN4O4 详情 详情
(XI) 61908 (3S,5R)-6-azido-3-[(tert-butoxycarbonyl)amino]-5-fluorohexanoic acid C11H19FN4O4 详情 详情
(XII) 61909 tert-butyl 2-(1-methylhydrazino)acetate C7H16N2O2 详情 详情
(XIII) 61910 tert-butyl (7S)-7-[(2S)-3-azido-2-fluoropropyl]-3,11,11-trimethyl-5,9-dioxo-10-oxa-3,4,6,8-tetraazadodecan-1-oate C17H32FN7O5 详情 详情
(XIV) 61911 tert-butyl (7R)-7-[(2R)-3-amino-2-fluoropropyl]-3,11,11-trimethyl-5,9-dioxo-10-oxa-3,4,6,8-tetraazadodecan-1-oate C17H34FN5O5 详情 详情
Extended Information