[(3aR,4R,6R,6aR)-6-Methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methanol -Drug Synthesis Database

【结构式】

【分子编号】10017

【品名】[(3aR,4R,6R,6aR)-6-Methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methanol

【CA登记号】4099-85-8

【分子式】C₉H₁₆O₅

【分子量】204.22304

【元素组成】C 52.93% H 7.9% O 39.17%

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：(II)

A total synthesis of (+)-sinefungin has been reported: The reaction of D-ribose (I) with acetone and methanol by means of CuSO4 and a catalytic amount of H2SO4 gives methyl 2,3-O-isopropylidene-beta-D-ribofuranoside (II), which is oxidized to the aldehyde (III) with oxalyl chloride in DMSO/dichloromethane. The Wittig condensation of (III) with triethyl phosphonoacetate (IV) by means of NaH in THF affords the unsaturated ester (V), which is hydrogenated with H2 over Pd/C in ethyl acetate and saponified with LiOH in methanol/water to give the propionic acid (VI). The condensation of (VI) with the chiral oxazolidone (VII) by means of pivaloyl chloride and triethylamine in THF yields the oxalidone (VIII). The stereoselective alkylation of (VIII) with allyl bromide by means of lithium hexamethyldisylazide in THF affords the 2(S)-allyl derivative (IX), which is hydrolyzed with LiOH in THF/water to the corresponding free acid (X). The Curtius degradation of the acid (X) by means of diphenyl phosphorazidate and benzyl alcohol gives the corresponding benzyloxycarbonylamino derivative (XI), which is benzylated with benzyl bromide to the fully protected compound (XII). The ozonolysis of the allyl double bond of (XII) with O3 in methanol/dichloromethane yields the aldehyde (XIII).

参考文献中间体

合成目标

【1】 Ghosh, A.K.; Liu, W.M.; Total synthesis of (+)-sinefungin. J Org Chem 1996, 61, 18, 6175.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	32112	3-iodo-1-propene;3-iodo-propen;allyl iodide	556-56-9	C₃H₅I	详情	详情
(I)	10016	D-Ribose; (3R,4S,5R)-5-(Hydroxymethyl)tetrahydro-2,3,4-furantriol; (2R,3R,4R)-2,3,4,5-Tetrahydroxypentanal	50-69-1	C₅H₁₀O₅	详情	详情
(II)	10017	[(3aR,4R,6R,6aR)-6-Methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methanol	4099-85-8	C₉H₁₆O₅	详情	详情
(III)	10018	(3aR,4S,6R,6aR)-6-Methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxole-4-carbaldehyde		C₉H₁₄O₅	详情	详情
(IV)	10019	Ethyl 2-(diethoxyphosphoryl)acetate; Triethyl phosphonoacetate	867-13-0	C₈H₁₇O₅P	详情	详情
(V)	10020	Ethyl (E)-3-[(3aR,4R,6R,6aR)-6-methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-2-propenoate		C₁₃H₂₀O₆	详情	详情
(VI)	10021	3-[(3aR,4R,6R,6aR)-6-Methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]propionic acid		C₁₁H₁₈O₆	详情	详情
(VII)	10022	[(3aS,8aR)-2-Oxo-8,8a-dihydro-2H-indeno[1,2-d][1,3]oxazol-3(3aH)-yl]lithium		C₁₀H₈LiNO₂	详情	详情
(VIII)	10023	(3aS,8aR)-3-[3-[(3aR,4R,6R,6aR)-6-Methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]propanoyl]-3,3a,8,8a-tetrahydro-2H-indeno[1,2-d][1,3]oxazol-2-one		C₂₁H₂₅NO₇	详情	详情
(IX)	10024	(3aS,8aR)-3-((2S)-2-[[(3aR,4R,6R,6aR)-6-Methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methyl]-4-pentenoyl)-3,3a,8,8a-tetrahydro-2H-indeno[1,2-d][1,3]oxazol-2-one		C₂₄H₂₉NO₇	详情	详情
(X)	10025	(2S)-2-[[(3aR,4R,6R,6aR)-6-Methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methyl]-4-pentenoic acid		C₁₄H₂₂O₆	详情	详情
(XI)	10026	Benzyl N-((1S)-1-[[(3aR,4R,6R,6aR)-6-methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methyl]-3-butenyl)carbamate	180776-29-8	C₂₁H₂₉NO₆	详情	详情
(XII)	10027	Benzyl (1S)-1-[[(3aR,4R,6R,6aR)-6-methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methyl]-3-butenyl(benzyl)carbamate		C₂₈H₃₅NO₆	详情	详情
(XIII)	10028	Benzyl (1R)-1-[[(3aR,4R,6R,6aR)-6-methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methyl]-3-oxopropyl(benzyl)carbamate		C₂₇H₃₃NO₇	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 oxidation of 1-O-mehyl 2,3-isopropylidene-D-ribofuranoside (I) gives the corresponding aldehyde (II), which is condensed with methyltriphenylphosphonium bromide by means of butyllithium in THF yielding methyl 5-deoxy-2,3-isopropylidene-5-methylene-D-ribofuranoside (III). Elimination of the isopropylidene protecting group by passing through an Amberlyst resin (acid form) affords the free ribofuranoside (IV), which is benzoylated with benzoyl chloride and triethylamine in dichloromethane to afford the dibenzoyl derivative (V). The methyl ribofuranoside (V) was converted into the 1-O-acetyl derivative (VI) and condensed with 2,6-dichloro-9H-purine (VII) by heating at 150 C to provide the dichloropurine derivative (VIII), which is treated with O-methylhydroxylamine and triethylamine to afford 2',3'-di-O-benzoyl-2-chloro-5'-deoxy-N-methoxy-5'-methyleneadenosine (IX). Finally, this compound is debenzoylated with ammonia in methanol.

参考文献中间体

合成目标

【1】 Lau, J.; Knutsen, L.J.S. (Novo Nordisk A/S); Chemical cpds., their preparation and use. EP 0719275; JP 1999511436; US 5589467; WO 9507921 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	10463	Benzoyl chloride	98-88-4	C₇H₅ClO	详情	详情
	15455	(aminooxy)methane; O-methylhydroxylamine	67-62-9	CH₅NO	详情	详情
(I)	10017	[(3aR,4R,6R,6aR)-6-Methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methanol	4099-85-8	C₉H₁₆O₅	详情	详情
(II)	10018	(3aR,4S,6R,6aR)-6-Methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxole-4-carbaldehyde		C₉H₁₄O₅	详情	详情
(III)	25257	(3aS,4R,6R,6aR)-4-methoxy-2,2-dimethyl-6-vinyltetrahydrofuro[3,4-d][1,3]dioxole; (3aS,4R,6R,6aR)-2,2-dimethyl-6-vinyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl methyl ether		C₁₀H₁₆O₄	详情	详情
(IV)	25258	(2R,3S,4S,5R)-2-methoxy-5-vinyltetrahydro-3,4-furandiol		C₇H₁₂O₄	详情	详情
(V)	25259	(2R,3R,4R,5R)-4-(benzoyloxy)-2-methoxy-5-vinyltetrahydro-3-furanyl benzoate		C₂₁H₂₀O₆	详情	详情
(VI)	25260	(2R,3R,4R,5S)-5-(acetoxy)-4-(benzoyloxy)-2-vinyltetrahydro-3-furanyl benzoate		C₂₂H₂₀O₇	详情	详情
(VII)	25254	2,6-dichloro-9H-purine	5451-40-1	C₅H₂Cl₂N₄	详情	详情
(VIII)	25261	(2R,3R,4S,5R)-4-(benzoyloxy)-2-(2,6-dichloro-9H-purin-9-yl)-5-vinyltetrahydro-3-furanyl benzoate		C₂₅H₁₈Cl₂N₄O₅	详情	详情
(IX)	25262	(2R,3R,4S,5R)-4-(benzoyloxy)-2-[2-chloro-6-(methoxyamino)-9H-purin-9-yl]-5-vinyltetrahydro-3-furanyl benzoate		C₂₆H₂₂ClN₅O₆	详情	详情

Extended Information