1-(tert-butyl) 2-[(1S,2E)-1-[(1R)-1-((4R,6R,9R)-9-{[tert-butyl(dimethyl)silyl]oxy}-2,2-dimethyl-1,3,7-trioxaspiro[5.5]undec-10-en-4-yl)ethyl]-3-((1R,3R,4R)-4-{[tert-butyl(diphenyl)silyl]oxy}-3-methoxycyclohexyl)-2-methyl-2-propenyl] (2S)-1,2-piperid -Drug Synthesis Database

【结构式】

【分子编号】57303

【品名】1-(tert-butyl) 2-[(1S,2E)-1-[(1R)-1-((4R,6R,9R)-9-{[tert-butyl(dimethyl)silyl]oxy}-2,2-dimethyl-1,3,7-trioxaspiro[5.5]undec-10-en-4-yl)ethyl]-3-((1R,3R,4R)-4-{[tert-butyl(diphenyl)silyl]oxy}-3-methoxycyclohexyl)-2-methyl-2-propenyl] (2S)-1,2-piperid

【CA登记号】

【分子式】C₅₆H₈₇NO₁₀Si₂

【分子量】990.47852

【元素组成】C 67.91% H 8.85% N 1.41% O 16.15% Si 5.67%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(VII)

The intermediate (IX) has been obtained as follows: The reduction of the spiroenone (I) with Li(s-Bu)3BH gives the corresponding alcohol that is protected with Tbdms-Cl and imidazole to yield the silyl ether (II). The oxidation of the vinyl group of (II) with OsO4, NaIO4 and NMO affords the carbaldehyde (III), which is condensed with the vinyl bromide (IV) by means of t-BuLi to provide the alcohol (V). The esterification of the alcohol (V) with the chiral piperidine-2-carboxylic acid (VI) by means of DCC and DMAP gives the ester (VII), which is selectively monodesilylated by means of TBAF to yield the alcohol (VIII). Finally this alcohol is oxidized by means of Dess Martin periodinane (DMP) to afford the target spiroenone (IX).

参考文献中间体

合成目标

【1】 Gleason, J.L.; The total synthesis of FK-506 and its spiroketal analogs. Diss Abstr Int B - Sci Eng 1994, 54, 12, Part 1, 6206.
【2】 Ireland, R.E.; et al.; A total synthesis of FK-506. J Org Chem 1996, 61, 20, 6856.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	57299	(4S,6R)-2,2-dimethyl-4-[(1S)-1-methyl-2-propenyl]-1,3,7-trioxaspiro[5.5]undec-10-en-9-one	C₁₄H₂₀O₄	详情	详情
(II)	57300	tert-butyl(dimethyl)silyl (4S,6R,9R)-2,2-dimethyl-4-[(1S)-1-methyl-2-propenyl]-1,3,7-trioxaspiro[5.5]undec-10-en-9-yl ether; tert-butyl({(4S,6R,9R)-2,2-dimethyl-4-[(1S)-1-methyl-2-propenyl]-1,3,7-trioxaspiro[5.5]undec-10-en-9-yl}oxy)dimethylsilane	C₂₀H₃₆O₄Si	详情	详情
(III)	57301	(2R)-2-((4S,6R,9R)-9-{[tert-butyl(dimethyl)silyl]oxy}-2,2-dimethyl-1,3,7-trioxaspiro[5.5]undec-10-en-4-yl)propanal	C₁₉H₃₄O₅Si	详情	详情
(IV)	17368	(1R,2R,5R)-5-[(E)-2-bromo-1-propenyl]-2-[[tert-butyl(diphenyl)silyl]oxy]cyclohexyl methyl ether; ([(1R,2R,4R)-4-[(E)-2-bromo-1-propenyl]-2-methoxycyclohexyl]oxy)(tert-butyl)diphenylsilane	C₂₆H₃₅BrO₂Si	详情	详情
(V)	57302	(E,3S,4S)-4-((4R,6R,9R)-9-{[tert-butyl(dimethyl)silyl]oxy}-2,2-dimethyl-1,3,7-trioxaspiro[5.5]undec-10-en-4-yl)-1-((1R,3R,4R)-4-{[tert-butyl(diphenyl)silyl]oxy}-3-methoxycyclohexyl)-2-methyl-1-penten-3-ol	C₄₅H₇₀O₇Si₂	详情	详情
(VI)	11487	(2S)-1-(tert-Butoxycarbonyl)hexahydro-2-pyridinecarboxylic acid	C₁₁H₁₉NO₄	详情	详情
(VII)	57303	1-(tert-butyl) 2-[(1S,2E)-1-[(1R)-1-((4R,6R,9R)-9-{[tert-butyl(dimethyl)silyl]oxy}-2,2-dimethyl-1,3,7-trioxaspiro[5.5]undec-10-en-4-yl)ethyl]-3-((1R,3R,4R)-4-{[tert-butyl(diphenyl)silyl]oxy}-3-methoxycyclohexyl)-2-methyl-2-propenyl] (2S)-1,2-piperid	C₅₆H₈₇NO₁₀Si₂	详情	详情
(VIII)	57304	1-(tert-butyl) 2-((1S,2E)-3-((1R,3R,4R)-4-{[tert-butyl(diphenyl)silyl]oxy}-3-methoxycyclohexyl)-1-{(1R)-1-[(4R,6R,9R)-9-hydroxy-2,2-dimethyl-1,3,7-trioxaspiro[5.5]undec-10-en-4-yl]ethyl}-2-methyl-2-propenyl) (2S)-1,2-piperidinedicarboxylate	C₅₀H₇₃NO₁₀Si	详情	详情
(IX)	57305	1-(tert-butyl) 2-((1S,2E)-3-((1R,3R,4R)-4-{[tert-butyl(diphenyl)silyl]oxy}-3-methoxycyclohexyl)-1-{(1R)-1-[(4R,6R)-2,2-dimethyl-9-oxo-1,3,7-trioxaspiro[5.5]undec-10-en-4-yl]ethyl}-2-methyl-2-propenyl) (2S)-1,2-piperidinedicarboxylate	C₅₀H₇₁NO₁₀Si	详情	详情

Extended Information