(1R,3R,4R)-3,4-dihydroxycyclohexanecarboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】45302

【品名】(1R,3R,4R)-3,4-dihydroxycyclohexanecarboxylic acid

【CA登记号】

【分子式】C₇H₁₂O₄

【分子量】160.16988

【元素组成】C 52.49% H 7.55% O 39.96%

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：(I)

The compound has been obtained biosynthetically by an optimized fermentation process using Streptomyces hygroscopicus mutant RSH 1701 with a complex culture medium were [14C]-labeled (1R,3R,4R)-2,3-dichydroxycyclo-hexanecarboxylic acid (I) and [14C]-labeled (S)-pipecolic acid (II) have been added. This fermentation process yielded [14C]-labeled rapamycin (III), which was finally selectively O-alkylated at the C-40 position with monosilylated ethylene glycol triflate in DMSO/dimethoxyethane.

参考文献中间体

合成目标

【1】 Moenius, T.; et al.; C-14 labelling of NVP RAD001 - A new rapamycin derivative. J Label Compd Radiopharm 1999, 42, 1, 29.

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)	32019	(1R,3R,4R)-3,4-dihydroxycyclohexanecarboxylic acid		C₇H₁₂O₄	详情	详情
(I)	45302	(1R,3R,4R)-3,4-dihydroxycyclohexanecarboxylic acid		C₇H₁₂O₄	详情	详情
(II)	17380	(2S)hexahydro-2-pyridinecarboxylic acid; (S)-pipecolic acid	3105-95-1	C₆H₁₁NO₂	详情	详情
(II)	45303	(2S)-2-piperidinecarboxylic acid		C₆H₁₁NO₂	详情	详情
(III)	20296	(1R,9S,12S,15R,18R,19R,21R,23S,30S,32S,35R)-1,18-dihydroxy-12-[(1R)-2-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]-1-methylethyl]-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.0(4,9)]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone	53123-88-9	C₅₁H₇₉NO₁₃	详情	详情
(III)	45304	(1R,9S,12S,15R,18R,19R,21R,23S,30S,32S,35R)-1,18-dihydroxy-12-[(1R)-2-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]-1-methylethyl]-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.0(4,9)]hexatriaconta-16,24,26,28-tetraene-2		C₅₁H₇₉NO₁₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The reaction of the labeled acylated (+)-bornane-10,2-sultam (IV) with triethyl phosphite gives the phosphonate (V), which is treated with paraformaldehyde, galvinoxyl and K2CO3 yielding the acrylate derivative (VI). The cyclization of (VI) with butadiene (VII) by means of diethylaluminum chloride and galvinoxyl (as radical scavenger) affords the cyclohexene-carboxamide derivative (VIII), which is hydrolyzed with LiOH in THF/water giving the (1R)-3-cyclohexenecarboxylic acid (IX). The oxidation of (IX) with m-chloroperbenzoic acid and triethylamine in CCl4 yielded regioselectively the hydroxylactone (X), which is finally hydrolyzed with HCl to the labeled intermediate (I).

参考文献中间体

合成目标

【1】 Moenius, T.; et al.; C-14 labelling of NVP RAD001 - A new rapamycin derivative. J Label Compd Radiopharm 1999, 42, 1, 29.

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)	32019	(1R,3R,4R)-3,4-dihydroxycyclohexanecarboxylic acid		C₇H₁₂O₄	详情	详情
(I)	45302	(1R,3R,4R)-3,4-dihydroxycyclohexanecarboxylic acid		C₇H₁₂O₄	详情	详情
(IV)	32020	(1S,5S)-4-(2-bromoacetyl)-10,10-dimethyl-3lambda(6)-thia-4-azatricyclo[5.2.1.0(1,5)]decane-3,3-dione		C₁₂H₁₈BrNO₃S	详情	详情
(IV)	45305	(1S,5S)-4-(2-bromoacetyl)-10,10-dimethyl-3lambda(6)-thia-4-azatricyclo[5.2.1.0(1,5)]decane-3,3-dione		C₁₂H₁₈BrNO₃S	详情	详情
(V)	32021	diethyl 2-[(1S,5S)-10,10-dimethyl-3,3-dioxo-3lambda(6)-thia-4-azatricyclo[5.2.1.0(1,5)]dec-4-yl]-2-oxoethylphosphonate		C₁₆H₂₈NO₆PS	详情	详情
(V)	45306	diethyl 2-[(1S,5S)-10,10-dimethyl-3,3-dioxo-3lambda(6)-thia-4-azatricyclo[5.2.1.0(1,5)]dec-4-yl]-2-oxoethylphosphonate		C₁₆H₂₈NO₆PS	详情	详情
(VI)	32022	(1S,5S)-4-acryloyl-10,10-dimethyl-3lambda(6)-thia-4-azatricyclo[5.2.1.0(1,5)]decane-3,3-dione		C₁₃H₁₉NO₃S	详情	详情
(VI)	45307	(1S,5S)-4-acryloyl-10,10-dimethyl-3lambda(6)-thia-4-azatricyclo[5.2.1.0(1,5)]decane-3,3-dione		C₁₃H₁₉NO₃S	详情	详情
(VII)	11579	1,3-Butadiene; Butadiene	106-99-0	C₄H₆	详情	详情
(VIII)	32023	(1S,5S)-4-[(1R)-3-cyclohexen-1-ylcarbonyl]-10,10-dimethyl-3lambda(6)-thia-4-azatricyclo[5.2.1.0(1,5)]decane-3,3-dione		C₁₇H₂₅NO₃S	详情	详情
(VIII)	45308	(1S,5S)-4-[(1R)-3-cyclohexen-1-ylcarbonyl]-10,10-dimethyl-3lambda(6)-thia-4-azatricyclo[5.2.1.0(1,5)]decane-3,3-dione		C₁₇H₂₅NO₃S	详情	详情
(IX)	11581	(1R)-3-Cyclohexene-1-carboxylic acid		C₇H₁₀O₂	详情	详情
(IX)	45309	(1R)-3-cyclohexene-1-carboxylic acid		C₇H₁₀O₂	详情	详情
(X)	11528	(1R,4R,5R)-4-Hydroxy-6-oxabicyclo[3.2.1]octan-7-one		C₇H₁₀O₃	详情	详情
(X)	45310	(1R,4R,5R)-4-hydroxy-6-oxabicyclo[3.2.1]octan-7-one		C₇H₁₀O₃	详情	详情

Extended Information