2-Sulfanyl-1-ethanol; 2-Mercaptoethanol -Drug Synthesis Database

【结构式】

【分子编号】36375

【品名】2-Sulfanyl-1-ethanol; 2-Mercaptoethanol

【CA登记号】60-24-2

【分子式】C₂H₆OS

【分子量】78.13504

【元素组成】C 30.74% H 7.74% O 20.48% S 41.04%

与该中间体有关的原料药合成路线共 6 条

合成路线1 合成路线2 合成路线3 合成路线4 合成路线5 合成路线6

合成路线1

该中间体在本合成路线中的序号：(XXI)

A new asymmetric synthesis has been reported. Oxidative cleavage of mono-benzoyl glycerol (IX) by means of NaIO4 provided aldehyde (X). Condensation of (X) with mercaptoethanol (XI) in the presence of ploystyryl diphenylphosphane-iodine complex gave rise to the oxathiolane (XII). Sharpless asymmetric oxidation of (XII) using tert-butyl hydroperoxide and L-diethyl tartrate led to an 82:18 mixture of (E)- and (Z)-sulfoxides (XIII) and (XIV). The desired (E)-isomer (XIII) was then isolated by column chromatography, displaying an enantiomeric excess of 60%. Coupling of (XIII) with N-acetylcytosine (VII) under Pummerer rearrangement conditions led to an equimolecular mixture of (Z)- and (E)-adducts (XV) and (XVI). After chromatographic separation of the desired (Z)-isomer (XV), the acetyl and benzoyl protecting groups were removed by treatment with sodium methoxide.

参考文献中间体

合成目标

【1】 Caputo, R.; et al.; A new strategy for the asymmetric synthesis of 1,3-oxathiolane-based nucleoside analogues. Eur J Org Chem 1999, 6, 1455.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VII)	55073	N(4)-Acetylcytosine	14631-20-0	C₆H₇N₃O₂	详情	详情
(IX)	55075	2,3-dihydroxypropyl benzoate		C₁₀H₁₂O₄	详情	详情
(X)	15605	2-oxoethyl benzoate		C₉H₈O₃	详情	详情
(XII)	55076	1,3-oxathiolan-2-ylmethyl benzoate		C₁₁H₁₂O₃S	详情	详情
(XIII)	55077	[(2R)-3-oxo-1,3lambda~4~-oxathiolan-2-yl]methyl benzoate		C₁₁H₁₂O₄S	详情	详情
(XIV)	55080	[(2S)-3-oxo-1,3lambda~4~-oxathiolan-2-yl]methyl benzoate		C₁₁H₁₂O₄S	详情	详情
(XV)	55078	{(2R,4R)-4-[4-(acetylamino)-2-oxo-1(2H)-pyrimidinyl]-1,3-oxathiolan-2-yl}methyl benzoate		C₁₇H₁₇N₃O₅S	详情	详情
(XVI)	55079	{(2R,4S)-4-[4-(acetylamino)-2-oxo-1(2H)-pyrimidinyl]-1,3-oxathiolan-2-yl}methyl benzoate		C₁₇H₁₇N₃O₅S	详情	详情
(XXI)	36375	2-Sulfanyl-1-ethanol; 2-Mercaptoethanol	60-24-2	C₂H₆OS	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Michael addition of 2-mercaptoethanol (II) to the unsaturated lactone function of (+)-brefeldin A (I) in the presence of Proton Sponge afforded the sulfanyl adduct (III). The title sulfoxide was then obtained by oxidation of sulfide (III) with meta-chloroperbenzoic acid.

参考文献中间体

合成目标

【1】 Fox, B.M.; et al.; Design and synthesis of (+)-brefeldin A sulfide prodrugs with enhanced aqueous solubilities. 222nd ACS Natl Meet (Aug 26 2001, Chicago) 2001, Abst MEDI 97.
【2】 Argade, A.B.; Devraj, R.; Vroman, J.A.; Haugwitz, R.D.; Hollingshead, M.; Cushman, M.; Design and synthesis of brefeldin A sulfide derivatives as prodrug candidates with enhanced aqueous solubilities. J Med Chem 1998, 41, 18, 3337.
【3】 Cushman, M.S.; Devraj, R.; Argade, A.B.; Haughwitz, R.D. (Purdue Research Foundation); Brefeldin A derivs.. US 6362218; WO 9931084 .

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)	53114	(1S,6S,11aS,13S,14aR)-1,13-dihydroxy-6-methyl-1,6,7,8,9,11a,12,13,14,14a-decahydro-4H-cyclopenta[f]oxacyclotridecin-4-one	n/a	C₁₆H₂₄O₄	详情	详情
(II)	36375	2-Sulfanyl-1-ethanol; 2-Mercaptoethanol	60-24-2	C₂H₆OS	详情	详情
(III)	53115	(1S,2R,6S,11aS,13S,14aR)-1,13-dihydroxy-2-[(2-hydroxyethyl)sulfanyl]-6-methyl-1,2,3,6,7,8,9,11a,12,13,14,14a-dodecahydro-4H-cyclopenta[f]oxacyclotridecin-4-one	n/a	C₁₈H₃₀O₅S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(III)

Halogenation of vitamin K3 (menadione) (I) by means of bromine and NaOAc in AcOH furnished 3-bromo menadione (II). Subsequent displacement of the halogen of (II) by 2-mercaptoethanol (III) in the presence of imidazole yielded the desired (2-hydroxyethyl) thioether.

参考文献中间体

合成目标

【1】 Kerns, J.K.; Carr, B.I.; Wilcox, C.S. (University of Pittsburgh); Antiproliferative naphthoquinones, derivs., compsns., and uses thereof. WO 0008495 .

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)	38865	menadione; 2-methylnaphthoquinone	58-27-5	C₁₁H₈O₂	详情	详情
(II)	38866	2-bromo-3-methylnaphthoquinone		C₁₁H₇BrO₂	详情	详情
(III)	36375	2-Sulfanyl-1-ethanol; 2-Mercaptoethanol	60-24-2	C₂H₆OS	详情	详情

合成路线4

该中间体在本合成路线中的序号：(III)

In an alternative procedure, the title compound was obtained by addition of 2-mercaptoethanol (III) to vitamin K3 oxide (menadione oxide) (IV) in the presence of imidazole.

参考文献中间体

合成目标

【1】 Horikawa, A.; et al.; Synthesis of protein tyrosine phosphatase inhibitor and application for malignant pediatric tumor. 21st Symp Med Chem (Nov 28 2001, Kyoto) 2001, Abst 2P-05.
【2】 Kerns, J.; Carr, B.; Dowd, P.; Finn, F.M.; Naganathan, s.; Thioalkyl derivatives of vitamin K3 and vitamin K3 oxide inhibit growth of Hep3B and HepG2 cells. Bioorganic Chemistry 1995, 23, 2, 101.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(III)	36375	2-Sulfanyl-1-ethanol; 2-Mercaptoethanol	60-24-2	C₂H₆OS	详情	详情
(IV)	38867	1a-methyl-1a,7a-dihydronaphtho[2,3-b]oxirene-2,7-dione		C₁₁H₈O₃	详情	详情

合成路线5

该中间体在本合成路线中的序号：(A)

The hydrogenation of ethyl 3-(2-furyl)acrylate (I) with H2 over Raney-Ni in ethanol gives ethyl 3-(2-furyl)propionate (II), which oxidative methoxylation with Br2 in methanol affords ethyl 3-(2,5-dimethoxy-2,5-dihydro-2-furyl)propionate (III). The partial reduction of (III) with diisobutylaluminum hydride in toluene yields the substituted propionaldehyde (IV), which by a Wittig condensation with 4-carboxybutyl triphenylphosphonium bromide by means of NaH in DMSO gives 8-(2,5-dimethoxy-2,5-dihydro-2-furyl)-5-octenoic acid (VI). The hydrolytic ring opening of (VI), followed by an aldol cyclization in refluxing dioxane - water by means of sodium acetate - NaH2PO4 - hydroquinone affords 7-(2-oxo-5-hydroxycyclopent-3-en-1-yl)-5-heptenoic acid (VII), which is isomerized by treatment with H2SO4 yielding 7-(5-oxo-3-hydroxycyclopenten-1-yl)-5-heptenoic acid (VIII). Methylation and esterification of (VIII) with H2SO4/refluxing methanol gives the methoxy methyl ester (IX), which by reaction with 2-mercaptoethanol (A) and sodium methoxide in methanol is converted into methyl 7-[5-oxo-3-(2-hydroxyethylthio)cyclopenten-1-yl]-5-heptenoate (X). The methylation of acid (VI) with NaH and methyl iodide gives the corresponding methyl ester (XIV), which is submitted to a hydrolytic ring opening and aldol cyclization as before to afford methyl 7-(2-oxo-5-hydroxycyclopent-3-en-1-yl)-5-heptenoate (XV). The silylation of (XV) with trimethylchlorosilane and hexamethyldisilazane as usual yields the corresponding trimethylsilyloxy derivative (XVI), which is treated with 2-mercaptoethanol (A) and sodium methoxide to give the isomerized compound (X).

参考文献中间体

合成目标

【1】 Floyd, M.B.; Prostaglandins and congeners. 18. Synthesis of cyclopentenolone precursors to prostaglandins from 2,5-dihydro-2,5-dimethoxyfurans. J Org Chem 1978, 43, 9, 1641-43.
【2】 Floyd, M.; et al.; Prostaglandins and congeners. 22. Synthesis of 11-substituted derivatives of 11-deoxyprostaglandins E1 and E2. Potential bronchodilators. J Med Chem 1980, 23, 8, 903-913.
【3】 Hillier, K.; Serradell, M.N.; Blancafort, P.; Castañer, J.; DHET-PGE2. Drugs Fut 1982, 7, 4, 241.
【4】 Weiss, M.J.; Siuta, G.J. (American Cyanamid Co.); 11-(2-Hydroxyethylthio)prostenoic acid E{HD 2 {B series derivatives. US 4085272 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	36375	2-Sulfanyl-1-ethanol; 2-Mercaptoethanol	60-24-2	C₂H₆OS	详情	详情
(I)	36362	ethyl (E)-3-(2-furyl)-2-propenoate	623-20-1	C₉H₁₀O₃	详情	详情
(II)	36363	ethyl 3-(2-furyl)propanoate	10031-90-0	C₉H₁₂O₃	详情	详情
(III)	36364	ethyl 3-(2,5-dimethoxy-2,5-dihydro-2-furanyl)propanoate		C₁₁H₁₈O₅	详情	详情
(IV)	36365	3-(2,5-dimethoxy-2,5-dihydro-2-furanyl)propanal		C₉H₁₄O₄	详情	详情
(V)	13616	(4-Carboxybutyl)triphenylphosphonium bromide	17814-85-6	C₂₃H₂₄BrO₂P	详情	详情
(VI)	36367	(Z)-8-(2,5-dimethoxy-2,5-dihydro-2-furanyl)-5-octenoic acid		C₁₄H₂₂O₅	详情	详情
(VII)	36368	(Z)-7-(2-hydroxy-5-oxo-3-cyclopenten-1-yl)-5-heptenoic acid		C₁₂H₁₆O₄	详情	详情
(VIII)	36369	(Z)-7-(3-hydroxy-5-oxo-1-cyclopenten-1-yl)-5-heptenoic acid		C₁₂H₁₆O₄	详情	详情
(IX)	36370	methyl (Z)-7-(3-methoxy-5-oxo-1-cyclopenten-1-yl)-5-heptenoate		C₁₄H₂₀O₄	详情	详情
(X)	36371	methyl (Z)-7-[3-[(2-hydroxyethyl)sulfanyl]-5-oxo-1-cyclopenten-1-yl]-5-heptenoate		C₁₅H₂₂O₄S	详情	详情
(XIV)	36372	methyl (Z)-8-(2,5-dimethoxy-2,5-dihydro-2-furanyl)-5-octenoate		C₁₅H₂₄O₅	详情	详情
(XV)	36373	methyl (Z)-7-(2-hydroxy-5-oxo-3-cyclopenten-1-yl)-5-heptenoate		C₁₃H₁₈O₄	详情	详情
(XVI)	36374	methyl (Z)-7-[2-oxo-5-[(trimethylsilyl)oxy]-3-cyclopenten-1-yl]-5-heptenoate		C₁₆H₂₆O₄Si	详情	详情

合成路线6

该中间体在本合成路线中的序号：(IV)

Condensation of 4,4'-dichlorobenzhydrol (I) with 2-bromoethanol (II) in the presence of sulfuric acid gave the bromopropyl ether (III), which was further condensed with 2-mercaptoethanol (IV), yielding thioether (V). Subsequent coupling of alcohol (V) with methyl 3-(4-hydroxyphenyl)propionate (VI) under Mitsunobu conditions furnished adduct (VII). Basic hydrolysis of the methyl ester function generated acid (VIII). After conversion of (VIII) to the corresponding acid chloride, its condensation with trifluoroacetic anhydride gave rise to the trifluoromethyl ketone (IX). The sulfide group of (X) was finally oxidized to the title sulfone using meta-chloroperbenzoic acid.

参考文献中间体

合成目标

【1】 Banville, J.; Burke, J.R.; Gai, Y.; Johnson, G.; Zusi, F.C. (Bristol-Myers Squibb Co.); Selective cPLA2 inhibitors. EP 1140791; WO 9915129 .

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)	50505	4,4'-Dichlorobenzhydrol; Bis(4-chlorophenyl)carbinol	90-97-1	C₁₃H₁₀Cl₂O	详情	详情
(II)	10059	Ethylene bromohydrin; 2-Bromo-1-ethanol	540-51-2	C₂H₅BrO	详情	详情
(III)	50506	1-[(2-bromoethoxy)(4-chlorophenyl)methyl]-4-chlorobenzene; bis(4-chlorophenyl)methyl 2-bromoethyl ether		C₁₅H₁₃BrCl₂O	详情	详情
(IV)	36375	2-Sulfanyl-1-ethanol; 2-Mercaptoethanol	60-24-2	C₂H₆OS	详情	详情
(V)	50507	2-([2-[bis(4-chlorophenyl)methoxy]ethyl]sulfanyl)-1-ethanol		C₁₇H₁₈Cl₂O₂S	详情	详情
(VI)	30341	methyl 3-(4-hydroxyphenyl)propanoate; 4-Hydroxyphenylpropionic acid methyl ester; 3-(4-Hydroxyphenyl)propionic acid methyl ester	5597-50-2	C₁₀H₁₂O₃	详情	详情
(VII)	50508	methyl 3-[4-[2-([2-[bis(4-chlorophenyl)methoxy]ethyl]sulfanyl)ethoxy]phenyl]propanoate		C₂₇H₂₈Cl₂O₄S	详情	详情
(VIII)	50509	3-[4-[2-([2-[bis(4-chlorophenyl)methoxy]ethyl]sulfanyl)ethoxy]phenyl]propionic acid		C₂₆H₂₆Cl₂O₄S	详情	详情
(IX)	50510	4-[4-[2-([2-[bis(4-chlorophenyl)methoxy]ethyl]sulfanyl)ethoxy]phenyl]-1,1,1-trifluoro-2-butanone		C₂₇H₂₅Cl₂F₃O₃S	详情	详情

Extended Information