(6R)-6-((1E,3R,4R,6R,7Z,9Z,11E)-3,6-bis[[tert-butyl(dimethyl)silyl]oxy]-13-[[tert-butyl(diphenyl)silyl]oxy]-4-hydroxy-3-methyl-1,7,9,11-tridecatetraenyl)-5,6-dihydro-2H-pyran-2-one -Drug Synthesis Database

【结构式】

【分子编号】49665

【品名】(6R)-6-((1E,3R,4R,6R,7Z,9Z,11E)-3,6-bis[[tert-butyl(dimethyl)silyl]oxy]-13-[[tert-butyl(diphenyl)silyl]oxy]-4-hydroxy-3-methyl-1,7,9,11-tridecatetraenyl)-5,6-dihydro-2H-pyran-2-one

【CA登记号】

【分子式】C₄₇H₇₂O₆Si₃

【分子量】817.34158

【元素组成】C 69.07% H 8.88% O 11.74% Si 10.31%

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：(XXXII)

The oxidation of alcohol (XXII) with DMP gives the corresponding aldehyde (XXIII), which is condensed with the lithium salt of diethyl methylphosphonate (XXIV), yielding the beta-hydroxy phosphonate (XXV). The oxidation of the OH group of (XXV) with DMP affords the corresponding ketone (XXVI), which is condensed with the already reported carbaldehyde intermediate (V) by means of potassium tert-butoxide to provide the adduct (XXVII). The methylation of the carbonyl group of (XXVII) with methyl lithium and CeCl3 gives tertiary alcohol (XXVIII), which is selectively monodesilylated with PPTS and ethanol (with simultaneous exchange of the isopropyl acetal group by an ethyl group), yielding the vicinal diol (XXIX). Under carefully controlled conditions, the monosilylation of the diol (XXIX) with Tbdms-OTf gives rise to tertiary silyl ether (XXX), which is treated with HCl to provide the lactol (XXXI). The oxidation of (XXXI) with silver carbonate affords the dihydropyranone (XXXII).

参考文献中间体

合成目标

【1】 Boger, D.L.; et al.; Total synthesis of fostriecin (CI-920). J Am Chem Soc 2001, 123, 18, 4161.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(V)	49639	(2R)-6-isopropoxy-3,6-dihydro-2H-pyran-2-carbaldehyde	C₉H₁₄O₃	详情	详情
(XXII)	49655	(2R,4R,5Z,7Z,9E)-4-[[tert-butyl(dimethyl)silyl]oxy]-11-[[tert-butyl(diphenyl)silyl]oxy]-2-[(triethylsilyl)oxy]-5,7,9-undecatrien-1-ol	C₃₉H₆₄O₄Si₃	详情	详情
(XXIII)	49656	(2R,4R,5Z,7Z,9E)-4-[[tert-butyl(dimethyl)silyl]oxy]-11-[[tert-butyl(diphenyl)silyl]oxy]-2-[(triethylsilyl)oxy]-5,7,9-undecatrienal	C₃₉H₆₂O₄Si₃	详情	详情
(XXIV)	49657	[(diethoxyphosphoryl)methyl]lithium	C₅H₁₂LiO₃P	详情	详情
(XXV)	49658	diethyl (3R,5R,6Z,8Z,10E)-5-[[tert-butyl(dimethyl)silyl]oxy]-12-[[tert-butyl(diphenyl)silyl]oxy]-2-hydroxy-3-[(triethylsilyl)oxy]-6,8,10-dodecatrienylphosphonate	C₄₄H₇₅O₇PSi₃	详情	详情
(XXVI)	49659	diethyl (3R,5R,6Z,8Z,10E)-5-[[tert-butyl(dimethyl)silyl]oxy]-12-[[tert-butyl(diphenyl)silyl]oxy]-2-oxo-3-[(triethylsilyl)oxy]-6,8,10-dodecatrienylphosphonate	C₄₄H₇₃O₇PSi₃	详情	详情
(XXVII)	49660	(1E,4R,6R,7Z,9Z,11E)-6-[[tert-butyl(dimethyl)silyl]oxy]-13-[[tert-butyl(diphenyl)silyl]oxy]-1-[(2R)-6-isopropoxy-3,6-dihydro-2H-pyran-2-yl]-4-[(triethylsilyl)oxy]-1,7,9,11-tridecatetraen-3-one	C₄₉H₇₆O₆Si₃	详情	详情
(XXVIII)	49661	(1E,3R,4R,6R,7Z,9Z,11E)-6-[[tert-butyl(dimethyl)silyl]oxy]-13-[[tert-butyl(diphenyl)silyl]oxy]-1-[(2R)-6-isopropoxy-3,6-dihydro-2H-pyran-2-yl]-3-methyl-4-[(triethylsilyl)oxy]-1,7,9,11-tridecatetraen-3-ol	C₅₀H₈₀O₆Si₃	详情	详情
(XXIX)	49662	(1E,3R,4R,6R,7Z,9Z,11E)-6-[[tert-butyl(dimethyl)silyl]oxy]-13-[[tert-butyl(diphenyl)silyl]oxy]-1-[(2R)-6-ethoxy-3,6-dihydro-2H-pyran-2-yl]-3-methyl-1,7,9,11-tridecatetraene-3,4-diol	C₄₃H₆₄O₆Si₂	详情	详情
(XXX)	49663	(5R,6R,8R,9Z,11Z,13E)-8-[[tert-butyl(dimethyl)silyl]oxy]-5-[(E)-2-[(2R)-6-ethoxy-3,6-dihydro-2H-pyran-2-yl]ethenyl]-2,2,3,3,5,18,18-heptamethyl-17,17-diphenyl-4,16-dioxa-3,17-disila-9,11,13-nonadecatrien-6-ol	C₄₉H₇₈O₆Si₃	详情	详情
(XXXI)	49664	(5R,6R,8R,9Z,11Z,13E)-8-[[tert-butyl(dimethyl)silyl]oxy]-5-[(E)-2-[(2R)-6-hydroxy-3,6-dihydro-2H-pyran-2-yl]ethenyl]-2,2,3,3,5,18,18-heptamethyl-17,17-diphenyl-4,16-dioxa-3,17-disila-9,11,13-nonadecatrien-6-ol	C₄₇H₇₄O₆Si₃	详情	详情
(XXXII)	49665	(6R)-6-((1E,3R,4R,6R,7Z,9Z,11E)-3,6-bis[[tert-butyl(dimethyl)silyl]oxy]-13-[[tert-butyl(diphenyl)silyl]oxy]-4-hydroxy-3-methyl-1,7,9,11-tridecatetraenyl)-5,6-dihydro-2H-pyran-2-one	C₄₇H₇₂O₆Si₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XXXII)

The reaction of the OH group of (XXXII) with PCl3, Pmb-OH and H2O2 gives the phosphoric triester (XXXIII), which is finally desilylated and debenzylated by treatments first with HF in acetonitrile/water (short time) to remove the PMB esters, and then with HF and pyridine in the same solvent to remove the silyl groups.

参考文献中间体

合成目标

【1】 Boger, D.L.; et al.; Total synthesis of fostriecin (CI-920). J Am Chem Soc 2001, 123, 18, 4161.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XXXII)	49665	(6R)-6-((1E,3R,4R,6R,7Z,9Z,11E)-3,6-bis[[tert-butyl(dimethyl)silyl]oxy]-13-[[tert-butyl(diphenyl)silyl]oxy]-4-hydroxy-3-methyl-1,7,9,11-tridecatetraenyl)-5,6-dihydro-2H-pyran-2-one		C₄₇H₇₂O₆Si₃	详情	详情
(XXXIII)	49666	(1R,3R,4Z,6Z,8E)-3-[[tert-butyl(dimethyl)silyl]oxy]-1-[(1R,2E)-1-[[tert-butyl(dimethyl)silyl]oxy]-1-methyl-3-[(2R)-6-oxo-3,6-dihydro-2H-pyran-2-yl]-2-propenyl]-10-[[tert-butyl(diphenyl)silyl]oxy]-4,6,8-decatrienyl bis(4-methoxybenzyl) phosphate		C₆₃H₈₉O₁₁PSi₃	详情	详情

Extended Information