(E,4S,5S)-5-[[tert-butyl(dimethyl)silyl]oxy]-6-[(2S,3S,4S,5S,6R,9S,11S)-9-ethyl-3,5,11-trimethyl-8-oxo-4-[(triethylsilyl)oxy]-1-oxa-7-azaspiro[5.5]undec-2-yl]-4-methyl-2-hexenal -Drug Synthesis Database

【结构式】

【分子编号】32430

【品名】(E,4S,5S)-5-[[tert-butyl(dimethyl)silyl]oxy]-6-[(2S,3S,4S,5S,6R,9S,11S)-9-ethyl-3,5,11-trimethyl-8-oxo-4-[(triethylsilyl)oxy]-1-oxa-7-azaspiro[5.5]undec-2-yl]-4-methyl-2-hexenal

【CA登记号】

【分子式】C₃₃H₆₃NO₅Si₂

【分子量】610.03796

【元素组成】C 64.97% H 10.41% N 2.3% O 13.11% Si 9.21%

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：(XVIII)

The condensation of (XIII) with the chiral borane (XIV) gives the addition product (XV), which is silylated with TBDMS-OTf affording (XVI). Ozonolysis of the double bond of (XVI) with O3 yields the aldehyde (XVII), which is condensed with TMS-CH2CH=N-t-Bu to provide he unsaturated aldehyde (XVIII).

参考文献中间体

合成目标

【1】 Nicolaou, K.C.; et al.; Total synthesis of sanglifehrin A. Angew Chem. Int Ed Engl 1999, 38, 16, 2447.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
	40677	N-(tert-butyl)-N-[(E)-2-(trimethylsilyl)ethylidene]amine; 2-methyl-N-[(E)-2-(trimethylsilyl)ethylidene]-2-propanamine	C₉H₂₁NSi	详情	详情
(XIII)	32425	2-[(2S,3S,4S,5S,6R,9S,11S)-9-ethyl-3,5,11-trimethyl-8-oxo-4-[(triethylsilyl)oxy]-1-oxa-7-azaspiro[5.5]undec-2-yl]acetaldehyde	C₂₂H₄₁NO₄Si	详情	详情
(XIV)	32426	(E)-2-butenyl[bis[(1S,2R,3S,5S)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]]borane	C₂₄H₄₁B	详情	详情
(XV)	32427	(2S,3S,4S,5S,6R,9S,11S)-9-ethyl-2-[(2S,3S)-2-hydroxy-3-methyl-4-pentenyl]-3,5,11-trimethyl-4-[(triethylsilyl)oxy]-1-oxa-7-azaspiro[5.5]undecan-8-one	C₂₆H₄₉NO₄Si	详情	详情
(XVI)	32428	(2S,3S,4S,5S,6R,9S,11S)-2-((2S,3S)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-methyl-4-pentenyl)-9-ethyl-3,5,11-trimethyl-4-[(triethylsilyl)oxy]-1-oxa-7-azaspiro[5.5]undecan-8-one	C₃₂H₆₃NO₄Si₂	详情	详情
(XVII)	32429	(2R,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-[(2S,3S,4S,5S,6R,9S,11S)-9-ethyl-3,5,11-trimethyl-8-oxo-4-[(triethylsilyl)oxy]-1-oxa-7-azaspiro[5.5]undec-2-yl]-2-methylbutanal	C₃₁H₆₁NO₅Si₂	详情	详情
(XVIII)	32430	(E,4S,5S)-5-[[tert-butyl(dimethyl)silyl]oxy]-6-[(2S,3S,4S,5S,6R,9S,11S)-9-ethyl-3,5,11-trimethyl-8-oxo-4-[(triethylsilyl)oxy]-1-oxa-7-azaspiro[5.5]undec-2-yl]-4-methyl-2-hexenal	C₃₃H₆₃NO₅Si₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XVIII)

The hydrogenation of the double bond of (XVIII) with H2 and Lindlar catalyst affords the corresponding saturated aldehyde (XIX), which is condensed with the diazophosphonate (XX) giving the acetylenic derivative (XXI). The bromination of (XXI) with N-bromosuccinimide (NBS) and AgNO3 yields the bromoacetylenic compound (XXII), which is desilylated with HF and TBAF affording the dihydroxy derivative (XXIII). The resilylation of (XXIII) with CF3CO-N(Me)-Tms gives the bis(trimethylsilyl) derivative (XXIV), which is finally converted into the desired intermediate, the stannane (XXV) by reaction with tributyltin hydride, PPh3 and Pd dibenzylideneacetone complex.

参考文献中间体

合成目标

【1】 Nicolaou, K.C.; et al.; Total synthesis of sanglifehrin A. Angew Chem. Int Ed Engl 1999, 38, 16, 2447.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
	21859	2,2,2-trifluoro-N-methyl-N-(trimethylsilyl)acetamide	C₆H₁₂F₃NOSi	详情	详情
(XVIII)	32430	(E,4S,5S)-5-[[tert-butyl(dimethyl)silyl]oxy]-6-[(2S,3S,4S,5S,6R,9S,11S)-9-ethyl-3,5,11-trimethyl-8-oxo-4-[(triethylsilyl)oxy]-1-oxa-7-azaspiro[5.5]undec-2-yl]-4-methyl-2-hexenal	C₃₃H₆₃NO₅Si₂	详情	详情
(XIX)	32431	(4S,5S)-5-[[tert-butyl(dimethyl)silyl]oxy]-6-[(2S,3S,4S,5S,6R,9S,11S)-9-ethyl-3,5,11-trimethyl-8-oxo-4-[(triethylsilyl)oxy]-1-oxa-7-azaspiro[5.5]undec-2-yl]-4-methylhexanal	C₃₃H₆₅NO₅Si₂	详情	详情
(XX)	32432	1-Diazo-2-oxopropylphosphonic acid dimethyl ester	C₅H₉N₂O₄P	详情	详情
(XXI)	32433	(2S,3S,4S,5S,6R,9S,11S)-2-((2S,3S)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-methyl-6-heptynyl)-9-ethyl-3,5,11-trimethyl-4-[(triethylsilyl)oxy]-1-oxa-7-azaspiro[5.5]undecan-8-one	C₃₄H₆₅NO₄Si₂	详情	详情
(XXII)	32434	(2S,3S,4S,5S,6R,9S,11S)-2-((2S,3S)-7-bromo-2-[[tert-butyl(dimethyl)silyl]oxy]-3-methyl-6-heptynyl)-9-ethyl-3,5,11-trimethyl-4-[(triethylsilyl)oxy]-1-oxa-7-azaspiro[5.5]undecan-8-one	C₃₄H₆₄BrNO₄Si₂	详情	详情
(XXIII)	32435	(2S,3R,4S,5S,6R,9S,11S)-2-[(2S,3S)-7-bromo-2-hydroxy-3-methyl-6-heptynyl]-9-ethyl-4-hydroxy-3,5,11-trimethyl-1-oxa-7-azaspiro[5.5]undecan-8-one	C₂₂H₃₆BrNO₄	详情	详情
(XXIV)	32436	(2S,3R,4S,5S,6R,9S,11S)-2-[(2S,3S)-7-bromo-3-methyl-2-[(trimethylsilyl)methyl]-6-heptynyl]-9-ethyl-3,5,11-trimethyl-4-[(trimethylsilyl)methyl]-1-oxa-7-azaspiro[5.5]undecan-8-one	C₃₀H₅₆BrNO₂Si₂	详情	详情
(XXV)	32437	(2S,3R,4S,5S,6R,9S,11S)-9-ethyl-3,5,11-trimethyl-2-[(2S,3S,6E)-3-methyl-7-(tributylstannyl)-2-[(trimethylsilyl)methyl]-6-heptenyl]-4-[(trimethylsilyl)methyl]-1-oxa-7-azaspiro[5.5]undecan-8-one	C₄₂H₈₅NO₂Si₂Sn	详情	详情

Extended Information