1,3-propanedithiol; 3-sulfanylpropylhydrosulfide -Drug Synthesis Database

【结构式】

【分子编号】29729

【品名】1,3-propanedithiol; 3-sulfanylpropylhydrosulfide

【CA登记号】109-80-8

【分子式】C₃H₈S₂

【分子量】108.22852

【元素组成】C 33.29% H 7.45% S 59.26%

与该中间体有关的原料药合成路线共 8 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7 合成路线8

合成路线1

该中间体在本合成路线中的序号：(XXX)

3) The cyclization of (R)-(+)-citronellal (XVIII) with ZnBr2 followed by reaction with diborane and H2O2 gives the diol (XI), which is selectively benzylated with benzyl chloride and NaH to the monobenzyl ether (XX). The oxidation of (XX) with the Jones reagent yields the cyclohexanone (XXI), which is condensed with 3-(trimethylsilyl)-3-buten-2-one (XXII) by means of lithium diisopropylamide to the dione (XXIII). The cyclization of (XXIII) by means of Ba(OH)2 and oxalic acid affords the benzylated octahydronaphthalenone (XXIV), which by reduction with NaBH4 followed by reoxidation with the Jones reagent gives the decalinone (XXV). The Grignard methylation of (XXV) with methylmagnesium iodide yields the tertiary alcohol (XXVI), which is dehydrated with p-toluenesulfonic acid to the octahydronaphthalene (XXVII). The debenzylation of (XXVII) with sodamide, followed by oxidation with the Jones reagent and methylation with diazomethane affords the ester (XXVIII), which is ozonolyzed with O3 to the formyl ketone (XXIX). Selective protection of the ketone group with propane-1,3-dithiol (XXX) and p-toluenesulfonic acid gives the substituted 1,3-dithiane (XXXI), which is treated with methyl orthoformate and p-toluenesulfonic acid to yield the methoxymethylene derivative (XXXII). The elimination of the dithiane group with HgCl2 in aqueous acetonitrile affords the ketoester (XXXIII), which is submitted to a photochemical oxidation using rose bengal as catalyst in methanol, giving the peroxide (XXXIV). Finally, this compound is cyclized by means of HClO4 and OsO4. 4) The benzylated octahydronaphthalenone (XXIV) can also be obtained by benzylation of the ketone (VIII) with benzyl bromide by means of NaH in DMF.

参考文献中间体

合成目标

【1】 Deshpande, V.H.; Bhonsle, J.B.; Pandey, B.; Ravindranathan, T.; New synthetic strategies towards (+)-artemisinin. Tetrahedron Lett 1994, 35, 30, 5489.

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)	10215	(3aS,6R,6aS,10aR)-3,6-Dimethyloctahydro-2H-naphtho[8a,1-b]furan-9(10H)-one		C₁₄H₂₂O₂	详情	详情
(XVIII)	10225	(3R)-3,7-Dimethyl-6-octenal; L-Citronellal	5949-05-3	C₁₀H₁₈O	详情	详情
(XIX)	10226	(1R,2S,5R)-2-(2-Hydroxy-1-methylethyl)-5-methylcyclohexanol		C₁₀H₂₀O₂	详情	详情
(XX)	10227	(1R,2S,5R)-2-[2-(Benzyloxy)-1-methylethyl]-5-methylcyclohexanol		C₁₇H₂₆O₂	详情	详情
(XXI)	10228	(2S,5R)-2-[2-(Benzyloxy)-1-methylethyl]-5-methylcyclohexanone		C₁₇H₂₄O₂	详情	详情
(XXII)	10229	3-(Trimethylsilyl)-3-buten-2-one		C₇H₁₄OSi	详情	详情
(XXIII)	10230	(2S,3R,6S)-6-[2-(Benzyloxy)-1-methylethyl]-3-methyl-2-(3-oxobutyl)cyclohexanone		C₂₁H₃₀O₃	详情	详情
(XXIV)	10231	(4aS,5R,8S)-8-[2-(Benzyloxy)-1-methylethyl]-5-methyl-4,4a,5,6,7,8-hexahydro-2(3H)-naphthalenone		C₂₁H₂₈O₂	详情	详情
(XXV)	10232	(4aS,5R,8R,8aS)-8-[2-(Benzyloxy)-1-methylethyl]-5-methyloctahydro-2(1H)-naphthalenone		C₂₁H₃₀O₂	详情	详情
(XXVI)	10233	(4aS,5R,8R,8aS)-8-[2-(Benzyloxy)-1-methylethyl]-2,5-dimethyldecahydro-2-naphthalenol		C₂₂H₃₄O₂	详情	详情
(XXVII)	10234	2-[(1R,4R,4aS,8aS)-4,7-Dimethyl-1,2,3,4,4a,5,6,8a-octahydro-1-naphthalenyl]propyl benzyl ether; (1R,4R,4aS,8aS)-1-[2-(Benzyloxy)-1-methylethyl]-4,7-dimethyl-1,2,3,4,4a,5,6,8a-octahydronaphthalene		C₂₂H₃₂O	详情	详情
(XXVIII)	10235	methyl 2-[(1R,4R,4aS,8aS)-4,7-dimethyl-1,2,3,4,4a,5,6,8a-octahydro-1-naphthalenyl]propanoate		C₁₆H₂₆O₂	详情	详情
(XXIX)	10236	methyl 2-[(1R,2S,3S,4R)-2-formyl-4-methyl-3-(3-oxobutyl)cyclohexyl]propanoate		C₁₆H₂₆O₄	详情	详情
(XXX)	29729	1,3-propanedithiol; 3-sulfanylpropylhydrosulfide	109-80-8	C₃H₈S₂	详情	详情
(XXXI)	10237	methyl 2-[(1R,2S,3S,4R)-2-formyl-4-methyl-3-[2-(2-methyl-1,3-dithian-2-yl)ethyl]cyclohexyl]propanoate		C₁₉H₃₂O₃S₂	详情	详情
(XXXII)	10238	methyl 2-[(1S,3S,4R)-2-[(Z)-methoxymethylidene]-4-methyl-3-[2-(2-methyl-1,3-dithian-2-yl)ethyl]cyclohexyl]propanoate		C₂₀H₃₄O₃S₂	详情	详情
(XXXIII)	10239	methyl 2-[(1S,3S,4R)-2-[(Z)-methoxymethylidene]-4-methyl-3-(3-oxobutyl)cyclohexyl]propanoate		C₁₇H₂₈O₄	详情	详情
(XXXIV)	10240	methyl 2-[(3R,5aS,6R,9S,9aR)-9a-(dimethoxymethyl)-3-methoxy-3,6-dimethyloctahydro-3H-1,2-benzodioxepin-9-yl]propanoate		C₁₉H₃₄O₇	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

3,4-Dimethoxybenzaldehyde (I) is treated with 1,3-propanedithiol (II) to give 2-(3,4-dimethoxyphenyl)-m-dithiane (III), the oxidation product of which (IV) is reacted with N-[2-(3,4-dimethoxyphenyl)ethyl]-N-methylpropanamine chloride (V) in the presence of a base.

参考文献中间体

合成目标

【1】 Ramuz, H.; DE 2460593 .
【2】 Ramuz, H.; A new Ca2+ antagonist, Ro-111781 and its metabolites. Synthesis and physicochemical properties. Arzneim-Forsch Drug Res 1978, 28, 11, 2048.
【3】 Koch, H.; Ro-11,1781. Drugs Fut 1979, 4, 2, 122.

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)	18304	3,4-Dimethoxybenzaldehyde; Veratraldehyde	120-14-9	C₉H₁₀O₃	详情	详情
(II)	29729	1,3-propanedithiol; 3-sulfanylpropylhydrosulfide	109-80-8	C₃H₈S₂	详情	详情
(III)	39515	2-(3,4-dimethoxyphenyl)-1,3-dithiane; 4-(1,3-dithian-2-yl)-2-methoxyphenyl methyl ether		C₁₂H₁₆O₂S₂	详情	详情
(IV)	39516	2-(3,4-dimethoxyphenyl)-1lambda(6),3lambda(6)-dithiane-1,1,3,3-tetrone		C₁₂H₁₆O₆S₂	详情	详情
(V)	29986	3-chloro-N-(3,4-dimethoxyphenethyl)-N-methyl-1-propanamine; N-(3-chloropropyl)-N-(3,4-dimethoxyphenethyl)-N-methylamine		C₁₄H₂₂ClNO₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(B)

The reaction of (-)-5-O-benzyl-2,3-O-isopropylidene-D-ribolactonle (I) with lithium dimethylmethylphosphonate in THF gives the hemiketal (II) in quantitative yield. Benzoylation of (II) with benzoyl chloride in pyridine leads to the acyclic dibenzoate (III), which is debenzoylated with methanolic sodium methoxide to afford the beta-ketophosphonate (IV). Oxidation of (IV) with the modified Collins' reagent (CrO3 - 2Py) in dichloromethane gives diketophosphonate (V). The reaction of (V) with powdered anhydrous potassium carbonate and 18-crown-6-ether in benzene under high dilution gives the 2-cyclopentenone (VI) (50% yield). Reduction of (VI) with sodium borohydride in a 0.4-M CeCl3 - 7H2O- methanol solution affords the allylic alcohol (VII) (85% yield), which is mesylated to give (VIII). The mesyl group on (VIII) is displaced by lithium azide to give the beta-azide (IX) (84% yield). Reduction of (IX) with 1,3-propanedithiol and triethylamine in absolute methanol gives the 2-cyclopentenylamine (X) (85% yield). Condensation of (X) with 5-amino-4,6-dichloropyrimidine in the presence of triethylamine (n-BuOH, reflux, 45 h) gives (XI) (52% yield). Ring closure with triethyl orthoformate and Ac2O or HCl gives (XII), which is treated with methanolic ammonia to afford (XIII) (overall yield 58%). Debenzylation of (XIII) with boron trichloride in dichloromethane leads to removal of the isopropylidene group (61% yield). Another method to obtain neplanocin A is also available, in which an enantioselective synthesis of neplanocin A is performed by a chemoenzymatic approach starting from the Diels-Alder adduct of cyclopentadiene and dimethyl acetylene-dicarboxylate.

参考文献中间体

合成目标

【1】 Arita, M.; Ito, Y.; Sawai, H.; Ohno, M.; Adachi, K.; Enantioselective synthesis of the carbocyclic nucleosides (-)-aristeromycin and (-)-neplanocin A by a chemicoenzymatic approach. J Am Chem Soc 1983, 105, 4049.
【2】 Lim, M.I.; Maquez, V.E.; Total synthesis of (-)-neplanocin A. Tetrahedron Lett 1981, 34, 4, 359-366.
【3】 Hayashi, M.; Yoshioka, H.; Yaginuma, S.; Nakatsu, K.; Studies on neplanocin A, new antitumor antibiotic. II. Structure determination. J Antibiot 1981, 34, 6, 675-680.
【4】 Fujimoto, S.; Neplanocin A. Drugs Fut 1985, 10, 10, 822.

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)	29720	[(dimethoxyphosphoryl)methyl]lithium		C₃H₈LiO₃P	详情	详情
(B)	29729	1,3-propanedithiol; 3-sulfanylpropylhydrosulfide	109-80-8	C₃H₈S₂	详情	详情
(I)	29719	6-(benzyloxy)-2,2-dimethyldihydrofuro[3,4-d][1,3]dioxol-4(3aH)-one		C₁₄H₁₆O₅	详情	详情
(II)	29721	dimethyl [6-(benzyloxy)-4-hydroxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methylphosphonate		C₁₇H₂₅O₈P	详情	详情
(III)	29722	(1R)-1-[(4S,5S)-5-[(E)-1-(benzoyloxy)-2-(dimethoxyphosphoryl)ethenyl]-2,2-dimethyl-1,3-dioxolan-4-yl]-2-(benzyloxy)ethyl benzoate		C₃₂H₃₅O₁₀P	详情	详情
(IV)	29723	dimethyl 2-[(4R,5R)-5-[(1R)-2-(benzyloxy)-1-hydroxyethyl]-2,2-dimethyl-1,3-dioxolan-4-yl]-2-oxoethylphosphonate		C₁₈H₂₇O₈P	详情	详情
(V)	29724	dimethyl 2-[(4R,5S)-5-[2-(benzyloxy)acetyl]-2,2-dimethyl-1,3-dioxolan-4-yl]-2-oxoethylphosphonate		C₁₈H₂₅O₈P	详情	详情
(VI)	29725	6-(benzyloxy)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-one		C₁₅H₁₆O₄	详情	详情
(VII)	29726	(4S)-6-(benzyloxy)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-ol		C₁₅H₁₈O₄	详情	详情
(VIII)	29727	(4S)-6-(benzyloxy)-2,2-dimethyl-4-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxole; benzyl (6S)-2,2-dimethyl-6-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-6,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl ether		C₁₈H₂₄O₄S	详情	详情
(IX)	29728	(6R)-6-azido-2,2-dimethyl-6,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl benzyl ether; (4R)-4-azido-6-(benzyloxy)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxole		C₁₅H₁₇N₃O₃	详情	详情
(X)	29730	(4R)-6-(benzyloxy)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-ylamine; (4R)-6-(benzyloxy)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-amine		C₁₅H₁₉NO₃	详情	详情
(XI)	29731	N-(5-amino-6-chloro-4-pyrimidinyl)-N-[6-(benzyloxy)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]amine; N(4)-[6-(benzyloxy)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-6-chloro-4,5-pyrimidinediamine		C₁₉H₂₁ClN₄O₃	详情	详情
(XII)	29732	9-[6-(benzyloxy)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-6-chloro-9H-purine; benzyl 6-(6-chloro-9H-purin-9-yl)-2,2-dimethyl-6,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl ether		C₂₀H₁₉ClN₄O₃	详情	详情
(XIII)	29733	9-[6-(benzyloxy)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-9H-purin-6-amine; 9-[6-(benzyloxy)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-9H-purin-6-ylamine		C₂₀H₂₁N₅O₃	详情	详情
(C)	22845	5-Amino-4,6-dichloropyrimidine; 4,6-dichloro-5-pyrimidinylamine; 4,6-dichloro-5-pyrimidinamine	5413-85-4	C₄H₃Cl₂N₃	详情	详情

合成路线4

该中间体在本合成路线中的序号：(L)

Dithiane intermediate (LII). The ozonolysis of the allylic diol (XLVIII) with O3 and PPh3 in dichloromethane/methanol gives the aldehyde (XLIX), which is condensed with propane-1,3-dithiol (L) by means of BF3/OEt2 in dichloromethane to yield the dihydroxylated 1,3-dithiane derivative (LI). Finally, this compound is protected with 3,4-Dmp-CHO (A) and PPTS to afford the desired dithiane intermediate (LII).

参考文献中间体

合成目标

【1】 Smith, A.B.; et al.; The spongistatins: Architecturally complex natural products - Part one: A formal synthesis of (+)-spongistatin 1 by construction of an advanced ABCD fragment. Angew Chem. Int Ed 2001, 40, 1, 191.

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)	46036	3,4-dimethylbenzaldehyde	5973-71-7	C₉H₁₀O	详情	详情
(XVIII)	64636	(2R,3R,4R)-1-{[tert-butyl(dimethyl)silyl]oxy}-2,4-dimethyl-5-hexen-3-ol		C₁₄H₃₀O₂Si	详情	详情
(XLIX)	64637	(2S,3S,4R)-5-{[tert-butyl(dimethyl)silyl]oxy}-3-hydroxy-2,4-dimethylpentanal		C₁₃H₂₈O₃Si	详情	详情
(L)	29729	1,3-propanedithiol; 3-sulfanylpropylhydrosulfide	109-80-8	C₃H₈S₂	详情	详情
(LI)	64638	(2R,3S,4S)-4-(1,3-dithian-2-yl)-2-methyl-1,3-pentanediol		C₁₀H₂₀O₂S₂	详情	详情
(LII)	64639	(4S,5R)-2-(3,4-dimethylphenyl)-4-[(1S)-1-(1,3-dithian-2-yl)ethyl]-5-methyl-1,3-dioxane		C₁₉H₂₈O₂S₂	详情	详情

合成路线5

该中间体在本合成路线中的序号：(V)

The omega iodoalkyl thiazole intermediate (XII) is obtained as follows: The cyclization of 2-hydroxypropionaldehyde dimethyl acetal (I) with acetaldehyde (II) by means of warm Dowex (H+) and catalyzed by 2-deoxyribose-5-phosphate aldolase (DERA) gives the chiral tetrahydrofuran derivative (III), which is acylated with Ac-Cl and pyridine to yield the acetoxy compound (IV). The reaction of (IV) with BF3/Et2O, propane-1,3-dithiol (V) and TiCl4 affords the protected dithiane (VI), which is oxidized with oxalyl chloride in DMSO to provide the ketone (VII). The Wittig condensation of (VII) with phosphine oxide (VIII) by means of BuLi in THF provides the protected alkyl thiazole (IX), which is treated with HgClO4 to cleave the dithiane ring and yield carbaldehyde (X). Finally, this aldehyde is coupled with iodomethylenephosphorane (XI) by means of NaHMDS in THF/HMPA to afford the target omega iodoalkyl thiazole intermediate (XII).

参考文献中间体

合成目标

【1】 Wong, C.-H.; Liu, J.; Aldolase-catalyzed asymmetric synthesis of novel pyranose synthons as a new entry to heterocycles and epothilones. Angew Chem. Int Ed 2002, 41, 8, 1404.

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)	54261	1,1-dimethoxy-2-propanol	42919-42-6	C₅H₁₂O₃	详情	详情
(II)	11974	Acetaldehyde	75-07-0	C₂H₄O	详情	详情
(III)	54262	(4S,5R)-5-methyltetrahydro-2,4-furandiol		C₅H₁₀O₃	详情	详情
(IV)	54263	(2R,3S)-5-hydroxy-2-methyltetrahydro-3-furanyl acetate	n/a	C₇H₁₂O₄	详情	详情
(V)	29729	1,3-propanedithiol; 3-sulfanylpropylhydrosulfide	109-80-8	C₃H₈S₂	详情	详情
(VI)	54264	(1S,2R)-1-(1,3-dithian-2-ylmethyl)-2-hydroxypropyl acetate	n/a	C₁₀H₁₈O₃S₂	详情	详情
(VII)	54265	(1S)-1-(1,3-dithian-2-ylmethyl)-2-oxopropyl acetate		C₁₀H₁₆O₃S₂	详情	详情
(VIII)	47000	(2-methyl-1,3-thiazol-4-yl)methyl(diphenyl)phosphine oxide; 4-[(diphenylphosphoryl)methyl]-2-methyl-1,3-thiazole		C₁₇H₁₆NOPS	详情	详情
(IX)	54266	(1S,2E)-1-(1,3-dithian-2-ylmethyl)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-2-propenyl acetate		C₁₅H₂₁NO₂S₃	详情	详情
(X)	44531	(1S,2E)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-1-(2-oxoethyl)-2-propenyl acetate		C₁₂H₁₅NO₃S	详情	详情
(XI)	44532	(iodomethylene)(triphenyl)phosphorane		C₁₉H₁₆IP	详情	详情
(XII)	44493	(1S,3Z)-4-iodo-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-butenyl acetate		C₁₃H₁₆INO₂S	详情	详情

合成路线6

该中间体在本合成路线中的序号：(A)

Treatment of cis-oxazolidine derivative (I) with isobutyraldehyde (II), LDA and LiBr in THF yields aldol product (III), which is then converted into (IV) by first aminal cleavage by means of MeOH and TfOH, followed by silylation with Tbdms-Cl and imidazole in DMF. Reaction of (IV) with formaldehyde and TsOH in benzene gives oxazolidine system (V), which is then first reduced with LiBH4 in THF/MeOH and then oxidized by means of DMSO, oxalyl chloride and Et3N in CH2Cl2 to provide aldehyde (VI). Mukaiyama aldol coupling of (VI) and (VII) in CH2Cl2 with MgI2 as catalyst, followed by treatment with K2CO3 in MeOH, yields aldol product (VIII), which is then converted into hydroxy lactam (IX) by the sequence: i) N-benzyl cleavage by hydrogenolysis over Pd/C in EtOH in the presence of DIEA; ii) ring closure by heating in MeOH; and iii) desilylation by treatment with HF in acetonitrile. Conversion of alcohol (IX) into dihydroxy acid (X) is achieved by a first oxidation with DMSO, oxalyl chloride and Et3N in CH2Cl2, followed by reaction with NaClO2, NaH2PO4 in t-BuOH and 2-Me-butene and final N/O methylene bridge removal with 1,3-propanedithiol (A) catalyzed by HCl and TFA. Compound (X) undergoes beta-lactonization to omuralide (XI) by means of BOPCl and Et3N in CH2Cl2 and finally (XI) is coupled to N-acetyl-L-cysteine (XII) in CH2Cl2 in the presence of Et3N.

参考文献中间体

合成目标

【1】 Corey, E.J.; Li, W.-D.Z.; Total synthesis and biological activity of lactacystin, omuralide and analogs. Chem Pharm Bull 1999, 47, 1, 1.

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)	29729	1,3-propanedithiol; 3-sulfanylpropylhydrosulfide	109-80-8	C₃H₈S₂	详情	详情
(I)	43582	methyl (2R,4S)-3-benzyl-2-(tert-butyl)-1,3-oxazolidine-4-carboxylate		C₁₆H₂₃NO₃	详情	详情
(II)	13226	2-Methylpropanal; Isobutyraldehyde	78-84-2	C₄H₈O	详情	详情
(III)	43583	methyl (2R,4R)-3-benzyl-2-(tert-butyl)-4-(1-hydroxy-2-methylpropyl)-1,3-oxazolidine-4-carboxylate		C₂₀H₃₁NO₄	详情	详情
(IV)	43584	methyl (2R,3S)-2-(benzylamino)-2-([[tert-butyl(dimethyl)silyl]oxy]methyl)-3-hydroxy-4-methylpentanoate		C₂₁H₃₇NO₄Si	详情	详情
(V)	43585	methyl (4R,5S)-3-benzyl-4-([[tert-butyl(dimethyl)silyl]oxy]methyl)-5-isopropyl-1,3-oxazolidine-4-carboxylate		C₂₂H₃₇NO₄Si	详情	详情
(VI)	43586	(4R,5S)-3-benzyl-4-([[tert-butyl(dimethyl)silyl]oxy]methyl)-5-isopropyl-1,3-oxazolidine-4-carbaldehyde		C₂₁H₃₅NO₃Si	详情	详情
(VII)	43587	(E)-1-methoxy-1-propenyl trimethylsilyl ether; [[(E)-1-methoxy-1-propenyl]oxy](trimethyl)silane	34880-70-1	C₇H₁₆O₂Si	详情	详情
(VIII)	43588	methyl (2R,3S)-3-[(4S,5S)-3-benzyl-4-([[tert-butyl(dimethyl)silyl]oxy]methyl)-5-isopropyl-1,3-oxazolidin-4-yl]-3-hydroxy-2-methylpropanoate		C₂₅H₄₃NO₅Si	详情	详情
(IX)	43589	(1S,6R,7S,7aS)-7-hydroxy-7a-(hydroxymethyl)-1-isopropyl-6-methyltetrahydro-5H-pyrrolo[1,2-c][1,3]oxazol-5-one		C₁₁H₁₉NO₄	详情	详情
(X)	43590	(2R,3S,4R)-3-hydroxy-2-[(1S)-1-hydroxy-2-methylpropyl]-4-methyl-5-oxo-2-pyrrolidinecarboxylic acid		C₁₀H₁₇NO₅	详情	详情
(XI)	43591	(1R,4R,5S)-1-[(1S)-1-hydroxy-2-methylpropyl]-4-methyl-6-oxa-2-azabicyclo[3.2.0]heptane-3,7-dione		C₁₀H₁₅NO₄	详情	详情
(XII)	43592	(2R)-2-(acetamido)-3-sulfanylpropionic acid		C₅H₉NO₃S	详情	详情

合成路线7

该中间体在本合成路线中的序号：(III)

Chiral oxazolidinone intermediate (VI): The oxidation of the terminal double bond of the chiral acyl oxazolidinone (I) with O2 catalyzed by CuCl and PdCl2 in DMF/water gives the ketone (II), which is ketalized with propane-1,3-dithiol (III) and Ts-OH in AcOH to yield the thioketal (IV). Finally, the stereocontrolled acylation of (IV) with propionyl chloride (V) by means of LDA in THF affords the target oxazolidinone intermediate (VI)

参考文献中间体

合成目标

【1】 Duan, M.S.; Paquette, L.A.; Highly diastereocontrolled synthesis of the C1-C25 domain of sanglifehrin A. Tetrahedron Lett 2000, 41, 20, 3789.

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)	60101	(4S)-4-benzyl-3-(5-hexenoyl)-1,3-oxazolidin-2-one		C₁₆H₁₉NO₃	详情	详情
(II)	60102	1-[(4S)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]-1,5-hexanedione		C₁₆H₁₉NO₄	详情	详情
(III)	29729	1,3-propanedithiol; 3-sulfanylpropylhydrosulfide	109-80-8	C₃H₈S₂	详情	详情
(IV)	60103	(4S)-4-benzyl-3-[4-(2-methyl-1,3-dithian-2-yl)butanoyl]-1,3-oxazolidin-2-one		C₁₉H₂₅NO₃S₂	详情	详情
(V)	15967	propanoyl chloride; propionyl chloride	79-03-8	C₃H₅ClO	详情	详情
(VI)	60104	(2R)-1-[(4S)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]-2-[2-(2-methyl-1,3-dithian-2-yl)ethyl]-1,3-pentanedione		C₂₂H₂₉NO₄S₂	详情	详情

合成路线8

该中间体在本合成路线中的序号：(V)

参考文献中间体

合成目标

【1】 Wong, C.-H.; Liu, J.; Aldolase-catalyzed asymmetric synthesis of novel pyranose synthons as a new entry to heterocycles and epothilones. Angew Chem. Int Ed 2002, 41, 8, 1404.

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)	54261	1,1-dimethoxy-2-propanol	42919-42-6	C₅H₁₂O₃	详情	详情
(II)	11974	Acetaldehyde	75-07-0	C₂H₄O	详情	详情
(III)	54262	(4S,5R)-5-methyltetrahydro-2,4-furandiol		C₅H₁₀O₃	详情	详情
(IV)	54263	(2R,3S)-5-hydroxy-2-methyltetrahydro-3-furanyl acetate	n/a	C₇H₁₂O₄	详情	详情
(V)	29729	1,3-propanedithiol; 3-sulfanylpropylhydrosulfide	109-80-8	C₃H₈S₂	详情	详情
(VI)	54264	(1S,2R)-1-(1,3-dithian-2-ylmethyl)-2-hydroxypropyl acetate	n/a	C₁₀H₁₈O₃S₂	详情	详情
(VII)	54265	(1S)-1-(1,3-dithian-2-ylmethyl)-2-oxopropyl acetate		C₁₀H₁₆O₃S₂	详情	详情
(VIII)	47000	(2-methyl-1,3-thiazol-4-yl)methyl(diphenyl)phosphine oxide; 4-[(diphenylphosphoryl)methyl]-2-methyl-1,3-thiazole		C₁₇H₁₆NOPS	详情	详情
(IX)	54266	(1S,2E)-1-(1,3-dithian-2-ylmethyl)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-2-propenyl acetate		C₁₅H₂₁NO₂S₃	详情	详情
(X)	44531	(1S,2E)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-1-(2-oxoethyl)-2-propenyl acetate		C₁₂H₁₅NO₃S	详情	详情
(XI)	44532	(iodomethylene)(triphenyl)phosphorane		C₁₉H₁₆IP	详情	详情
(XII)	44493	(1S,3Z)-4-iodo-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-butenyl acetate		C₁₃H₁₆INO₂S	详情	详情

Extended Information