(3R)-3,6-bis{[(benzyloxy)carbonyl]amino}hexanoic acid -Drug Synthesis Database

【结构式】

【分子编号】61219

【品名】(3R)-3,6-bis{[(benzyloxy)carbonyl]amino}hexanoic acid

【CA登记号】

【分子式】C₂₂H₂₆N₂O₆

【分子量】414.45832

【元素组成】C 63.76% H 6.32% N 6.76% O 23.16%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(III)

Protection of (R)-beta-lysine (I) by means of benzyl S-(4,6-dimethylpyrimidin-2-yl)thiol carbonate (II) affords the bis-(benzyloxycarbonyl) derivative (III). After activation of the carboxyl group of (III) as the corresponding succinimidyl ester (IV), its coupling with 1-methylhydrazinoacetic acid (V) furnishes hydrazide (VI). The benzyloxycarbonyl protecting groups of (VI) are finally removed by catalytic hydrogenolysis to provide the title compound.

参考文献中间体

合成目标

【1】 Umezawa, H.; Kondo, S. (Microbial Chemistry Research Foundation); delta-Substd. negamycin derivs. and syntheses. US 4065495 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	61218	(3R)-3,6-diaminohexanoic acid	C₆H₁₄N₂O₂	详情	详情
(II)	32266	O-benzyl S-(4,6-dimethyl-2-pyrimidinyl) carbonothioate; benzyl S-4,6-dimethylpyrimidin-2-ylthiolcarbonate	C₁₄H₁₄N₂O₂S	详情	详情
(III)	61219	(3R)-3,6-bis{[(benzyloxy)carbonyl]amino}hexanoic acid	C₂₂H₂₆N₂O₆	详情	详情
(IV)	61220	benzyl (1R)-4-{[(benzyloxy)carbonyl]amino}-1-{2-[(2,5-dioxo-1-pyrrolidinyl)oxy]-2-oxoethyl}butylcarbamate	C₂₆H₂₉N₃O₈	详情	详情
(V)	61221	2-(1-methylhydrazino)acetic acid	C₃H₈N₂O₂	详情	详情
(VI)	61222	2-[2-((3R)-3,6-bis{[(benzyloxy)carbonyl]amino}hexanoyl)-1-methylhydrazino]acetic acid	C₂₅H₃₂N₄O₇	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

In an alternative method, N,N'-bis-(benzyloxycarbonyl)-(R)-ornithine (I) is treated with PCl5 to afford the corresponding acid chloride, which is then converted to diazo ketone (II) with ethereal diazomethane. Rearrangement of (II) under Arndt-Eistert conditions in the presence of silver benzoate leads to the beta-lysine derivative (III). After saponification of the methyl ester (III), the resultant carboxylic acid (IV) is coupled to ethyl 1-methylhydrazinoacetate (V) via the mixed anhydride with isobutyl chloroformate, to give hydrazide (VI). Alkaline hydrolysis of the ethyl ester (VI) yields acid (VII). The N-carbobenzoxy groups are finally removed by hydrogenolysis to furnish the title compound.

参考文献中间体

合成目标

【1】 Curran, W.V.; Boothe, J.H.; The synthesis of deoxynegamycin and some related compounds. J Antibiot 1978, 31, 9, 914.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	61228	(2R)-2,5-bis{[(benzyloxy)carbonyl]amino}pentanoic acid	C₂₁H₂₄N₂O₆	详情	详情
(II)	61229		C₂₂H₂₄N₄O₅	详情	详情
(III)	61230	methyl (3R)-3,6-bis{[(benzyloxy)carbonyl]amino}hexanoate	C₂₃H₂₈N₂O₆	详情	详情
(IV)	61219	(3R)-3,6-bis{[(benzyloxy)carbonyl]amino}hexanoic acid	C₂₂H₂₆N₂O₆	详情	详情
(V)	61231	ethyl 2-(1-methylhydrazino)acetate	C₅H₁₂N₂O₂	详情	详情
(VI)	61232	ethyl 2-[2-((3R)-3,6-bis{[(benzyloxy)carbonyl]amino}hexanoyl)-1-methylhydrazino]acetate	C₂₇H₃₆N₄O₇	详情	详情
(VII)	61222	2-[2-((3R)-3,6-bis{[(benzyloxy)carbonyl]amino}hexanoyl)-1-methylhydrazino]acetic acid	C₂₅H₃₂N₄O₇	详情	详情

Extended Information