(2R)-6-isopropoxy-3,6-dihydro-2H-pyran-2-carbaldehyde -Drug Synthesis Database

【结构式】

【分子编号】49639

【品名】(2R)-6-isopropoxy-3,6-dihydro-2H-pyran-2-carbaldehyde

【CA登记号】

【分子式】C₉H₁₄O₃

【分子量】170.20836

【元素组成】C 63.51% H 8.29% O 28.2%

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：(V)

The synthesis of dihydropyrancarbaldehyde intermediate (V) has been performed as follows: The oxidation of the selenium derivative (I) with H2O2 followed by in situ elimination gives the dihydropyranone (II), which is reduced with DIBAL to the corresponding lactol and protected as the isopropyl ether (III) by means of PPTS and isopropanol. The deprotection of the silyl ether of (III) with TBAF affords the carbinol (IV), which is finally oxidized with TPAP and NMO to provide the desired carbaldehyde intermediate (V).

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
(I)	49635	(6R)-6-([[tert-butyl(diphenyl)silyl]oxy]methyl)-3-(phenylselanyl)tetrahydro-2H-pyran-2-one	C₂₈H₃₂O₃SeSi	详情	详情
(II)	49636	(6R)-6-([[tert-butyl(diphenyl)silyl]oxy]methyl)-5,6-dihydro-2H-pyran-2-one	C₂₂H₂₆O₃Si	详情	详情
(III)	49637	tert-butyl[[(2R)-6-isopropoxy-3,6-dihydro-2H-pyran-2-yl]methoxy]diphenylsilane; tert-butyl(diphenyl)silyl [(2R)-6-isopropoxy-3,6-dihydro-2H-pyran-2-yl]methyl ether	C₂₅H₃₄O₃Si	详情	详情
(IV)	49638	[(2R)-6-isopropoxy-3,6-dihydro-2H-pyran-2-yl]methanol	C₉H₁₆O₃	详情	详情
(V)	49639	(2R)-6-isopropoxy-3,6-dihydro-2H-pyran-2-carbaldehyde	C₉H₁₄O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

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

Extended Information