palmitic acid -Drug Synthesis Database

【结构式】

【分子编号】27918

【品名】palmitic acid

【CA登记号】57-10-3

【分子式】C₁₆H₃₂O₂

【分子量】256.42888

【元素组成】C 74.94% H 12.58% O 12.48%

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：(V)

CS-682 has been synthesized by several related ways: 1) By acylation of 2'-cyano-2'-deoxy-1-(beta-D-arabinofuranosyl)cytosine (I) with hexadecanoyl chloride (II) and trimethylsilyl chloride in pyridine. 2) By acylation of 2'-cyano-2'-deoxy-1-(beta-D-arabinofuranosyl)cytosine (I) with hexadecanoyl anhydride (III) in hot DMF. 3) The protection of the OH groups of 2'-cyano-2'-deoxy-1-(beta-D-arabinofuranosyl)cytosine (I) with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane in pyridine gives the 3',5'-cyclic disiloxane (IV), which is acylated by means of hexadecanoic acid (V) and DCC in THF, yielding the silylated compound (VI). Finally, this compound is deprotected with tetrabutylammonium fluoride (TBAF) in acetic acid.

参考文献中间体

合成目标

【1】 Castaner, J.; Hoshi, A.; CS-682. Drugs Fut 1999, 24, 9, 957.
【2】 Kaneko, M.; Hotoda, H.; Shibata, T.; Kobayashi, T.; Mitsuhashi, Y.; Matsuda, A.; Sasaki, T. (Sankyo Co., Ltd.); Pyrimidine nucleoside derivs. having anti-tumor activity, their preparation and use. EP 0536936; JP 1993194497; US 5691319 .

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)	27915	(2R,3S,4S,5R)-2-[4-amino-2-oxo-1(2H)-pyrimidinyl]-4-hydroxy-5-(hydroxymethyl)tetrahydro-3-furancarbonitrile		C₁₀H₁₂N₄O₄	详情	详情
(II)	16480	Palmitoyl Chloride; hexadecanoyl chloride	112-67-4	C₁₆H₃₁ClO	详情	详情
(III)	27916	hexadecanoic anhydride	623-65-4	C₃₂H₆₂O₃	详情	详情
(IV)	27917	(6aR,8R,9S,9aS)-8-[4-amino-2-oxo-1(2H)-pyrimidinyl]-2,2,4,4-tetraisopropyltetrahydro-6H-furo[3,2-f][1,3,5,2,4]trioxadisilocine-9-carbonitrile		C₂₂H₃₈N₄O₅Si₂	详情	详情
(V)	27918	palmitic acid	57-10-3	C₁₆H₃₂O₂	详情	详情
(VI)	27919	N-[1-[(6aR,8R,9S,9aS)-9-cyano-2,2,4,4-tetraisopropyltetrahydro-6H-furo[3,2-f][1,3,5,2,4]trioxadisilocin-8-yl]-2-oxo-1,2-dihydro-4-pyrimidinyl]hexadecanamide		C₃₈H₆₈N₄O₆Si₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

An efficient synthesis of the optically active compound has been reported. Acid hydrolysis of the chiral acetonide (I) gave dihydroxy ester (II), which was selectively protected at the primary hydroxyl group as the O-trityl derivative (III). The beta-keto thioester (V) was obtained by condensation of palmitic acid (IV) with the magnesium salt of [(tert-butylthio)carbonyl]acetic acid via activation with carbonyl diimidazole. Silver salt-promoted condensation of thioester (V) with hydroxy ester (III) gave adduct (VI). The 3-acyltetronic acid system (VII) was obtained by cyclization of (VI) in the presence of tetrabutylammonium fluoride. Finally, deprotection of the trityl group using 1 N HCl afforded the title compound.

参考文献中间体

合成目标

【1】 Sodeoka, M.; et al.; Asymmetric synthesis of a 3-acyltetronic acid derivative, RK-682, and formation of its calcium salt during silica gel column chromatography. Chem Pharm Bull 2001, 49, 2, 206.

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)	20917	methyl (4R)-2,2-dimethyl-1,3-dioxolane-4-carboxylate	52373-72-5	C₇H₁₂O₄	详情	详情
(II)	20916	methyl (2R)-2,3-dihydroxypropanoate		C₄H₈O₄	详情	详情
(III)	46955	methyl (2R)-2-hydroxy-3-(trityloxy)propanoate		C₂₃H₂₂O₄	详情	详情
(IV)	27918	palmitic acid	57-10-3	C₁₆H₃₂O₂	详情	详情
(V)	46956	S-(tert-butyl) 3-oxooctadecanethioate		C₂₂H₄₂O₂S	详情	详情
(VI)	46957	(1R)-2-methoxy-2-oxo-1-[(trityloxy)methyl]ethyl 3-oxooctadecanoate		C₄₁H₅₄O₆	详情	详情
(VII)	46958	(5R)-3-palmitoyl-5-[(trityloxy)methyl]-2,4(3H,5H)-furandione		C₄₀H₅₀O₅	详情	详情

Extended Information