(6R)-6-{(1E,3R,4R,6R,7Z)-6-{[tert-butyl(dimethyl)silyl]oxy}-4-hydroxy-8-iodo-3-methyl-3-[(triethylsilyl)oxy]-1,7-octadienyl}-5,6-dihydro-2H-pyran-2-one -Drug Synthesis Database

【结构式】

【分子编号】55495

【品名】(6R)-6-{(1E,3R,4R,6R,7Z)-6-{[tert-butyl(dimethyl)silyl]oxy}-4-hydroxy-8-iodo-3-methyl-3-[(triethylsilyl)oxy]-1,7-octadienyl}-5,6-dihydro-2H-pyran-2-one

【CA登记号】

【分子式】C₂₆H₄₇IO₅Si₂

【分子量】622.73165

【元素组成】C 50.15% H 7.61% I 20.38% O 12.85% Si 9.02%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(XX)

The selective deprotection of the Pmb- group of (XVIII) with DDQ in dichloromethane gives the secondary alcohol (XIX), which is submitted to a highly selective diimide reduction of its ethynylene group by means of 2-nitrobenzenesulfonyl hydrazide (NBSH) in THF/iPr-OH to yield the cis-iodovinyl compound (XX). The condensation of the iodovinyl compound (XX) with tributylstannane (XXI) by means of PdCl2(acetonitrile)2 in DMF affords the adduct (XXII), which is treated with PCl3/pyridine and then oxidized with tBu-OOH and Pmb-OH to provide the phosphate ester (XXIII). Finally, this compound is deprotected with HF/pyridine in acetonitrile to give the target fostriecin.

参考文献中间体

合成目标

【1】 Jacobsen, E.N.; Chavez, D.E.; Total synthesis of fostriecin (CI-920). Angew Chem. Int Ed 2001, 40, 19, 3667.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XVIII)	55492	(6R)-6-{(E,3R,4R,6R)-6-{[tert-butyl(dimethyl)silyl]oxy}-8-iodo-4-[(4-methoxybenzyl)oxy]-3-methyl-3-[(triethylsilyl)oxy]-1-octen-7-ynyl}-5,6-dihydro-2H-pyran-2-one	C₃₄H₅₃IO₆Si₂	详情	详情
(XIX)	55494	(6R)-6-{(E,3R,4R,6R)-6-{[tert-butyl(dimethyl)silyl]oxy}-4-hydroxy-8-iodo-3-methyl-3-[(triethylsilyl)oxy]-1-octen-7-ynyl}-5,6-dihydro-2H-pyran-2-one	C₂₆H₄₅IO₅Si₂	详情	详情
(XX)	55495	(6R)-6-{(1E,3R,4R,6R,7Z)-6-{[tert-butyl(dimethyl)silyl]oxy}-4-hydroxy-8-iodo-3-methyl-3-[(triethylsilyl)oxy]-1,7-octadienyl}-5,6-dihydro-2H-pyran-2-one	C₂₆H₄₇IO₅Si₂	详情	详情
(XXI)	55496	tert-butyl(diphenyl)silyl (2E,4Z)-5-(trimethylstannyl)-2,4-pentadienyl ether; tert-butyl(diphenyl){[(2E,4Z)-5-(trimethylstannyl)-2,4-pentadienyl]oxy}silane	C₂₄H₃₄OSiSn	详情	详情
(XXII)	55497	(6R)-6-{(1E,3R,4R,6R,7Z,9Z,11E)-6-{[tert-butyl(dimethyl)silyl]oxy}-13-{[tert-butyl(diphenyl)silyl]oxy}-4-hydroxy-3-methyl-3-[(triethylsilyl)oxy]-1,7,9,11-tridecatetraenyl}-5,6-dihydro-2H-pyran-2-one	C₄₇H₇₂O₆Si₃	详情	详情
(XXIII)	55498	(1R,3R,4Z,6Z,8E)-3-{[tert-butyl(dimethyl)silyl]oxy}-10-{[tert-butyl(diphenyl)silyl]oxy}-1-{(1R,2E)-1-methyl-3-[(2R)-6-oxo-3,6-dihydro-2H-pyran-2-yl]-1-[(triethylsilyl)oxy]-2-propenyl}-4,6,8-decatrienyl bis(4-methoxybenzyl) phosphate	C₆₃H₈₉O₁₁PSi₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XII)

The reaction of the iodovinyl compound (I) with BuLi and MgBr2 gives the organometallic compound (II), which is condensed with the acetylenic ketone (III) to yield the tertiary alcohol (IV). The selective monodesilylation of (IV) by means of HF affords the diol (V), which is selectively monoesterified with acryloyl chloride (VI) by means of DIEA to provide the acrylate (VII). The silylation of the free OH group of (VIII) with Tes-OTf gives the desilylated compound (VIII), which is submitted to a ring closing metathesis by means of (Pcy3)2RuCl2(=CH-PH) and Ti(O-iPr)4 in dichloromethane to yield the dihydropyranone (IX). The iodination of the terminal acetylene group of (IX) by means of NIS and AgNO3 in acetone affords the iodoacetylene (X), which is selectively deprotected at the Pmb protecting group by means of DDQ to provide the alcohol (XI). Finally the triple bond of (XI) is reduced by means of o-(NO2)C6H4-SO2-N=NH to obtain the target iodovinyl intermediate (XII) (see scheme no. 09093803b, intermediate (XX)).

参考文献中间体

合成目标

【1】 Wang, Y.-G.; Kobayashi, Y.; Formal total synthesis of fostriecin. Org Lett 2002, 4, 26, 4615.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	60531	(1R)-1-[(E)-2-iodoethenyl]-3-butenyl triethylsilyl ether; triethyl({(1R)-1-[(E)-2-iodoethenyl]-3-butenyl}oxy)silane		C₁₂H₂₃IOSi	详情	详情
(II)	60532	bromo{(1E,3R)-3-[(triethylsilyl)oxy]-1,5-hexadienyl}magnesium		C₁₂H₂₃BrMgOSi	详情	详情
(III)	60533	(3R,5R)-5-{[tert-butyl(dimethyl)silyl]oxy}-3-[(4-methoxybenzyl)oxy]-6-heptyn-2-one		C₂₁H₃₂O₄Si	详情	详情
(IV)	60534	(5R,6E,8R,9R,11R)-5-allyl-3,3-diethyl-11-ethynyl-9-[(4-methoxybenzyl)oxy]-8,13,13,14,14-pentamethyl-4,12-dioxa-3,13-disila-6-pentadecen-8-ol		C₃₃H₅₆O₅Si₂	详情	详情
(V)	60535	(4R,5E,7R,8R,10R)-10-{[tert-butyl(dimethyl)silyl]oxy}-8-[(4-methoxybenzyl)oxy]-7-methyl-1,5-dodecadien-11-yne-4,7-diol		C₂₇H₄₂O₅Si	详情	详情
(VI)	11577	Acryloyl chloride; Acrylyl chloride;2-Propenoyl chloride	814-68-6	C₃H₃ClO	详情	详情
(VII)	60536	(1R,2E,4R,5R,7R)-1-allyl-7-{[tert-butyl(dimethyl)silyl]oxy}-4-hydroxy-5-[(4-methoxybenzyl)oxy]-4-methyl-2-nonen-8-ynyl acrylate		C₃₀H₄₄O₆Si	详情	详情
(VIII)	60537	(1R,2E,4R,5R,7R)-1-allyl-7-{[tert-butyl(dimethyl)silyl]oxy}-5-[(4-methoxybenzyl)oxy]-4-methyl-4-[(triethylsilyl)oxy]-2-nonen-8-ynyl acrylate		C₃₆H₅₈O₆Si₂	详情	详情
(IX)	60538	(6R)-6-{(E,3R,4R,6R)-6-{[tert-butyl(dimethyl)silyl]oxy}-4-[(4-methoxybenzyl)oxy]-3-methyl-3-[(triethylsilyl)oxy]-1-octen-7-ynyl}-5,6-dihydro-2H-pyran-2-one		C₃₄H₅₄O₆Si₂	详情	详情
(X)	55492	(6R)-6-{(E,3R,4R,6R)-6-{[tert-butyl(dimethyl)silyl]oxy}-8-iodo-4-[(4-methoxybenzyl)oxy]-3-methyl-3-[(triethylsilyl)oxy]-1-octen-7-ynyl}-5,6-dihydro-2H-pyran-2-one		C₃₄H₅₃IO₆Si₂	详情	详情
(XI)	55494	(6R)-6-{(E,3R,4R,6R)-6-{[tert-butyl(dimethyl)silyl]oxy}-4-hydroxy-8-iodo-3-methyl-3-[(triethylsilyl)oxy]-1-octen-7-ynyl}-5,6-dihydro-2H-pyran-2-one		C₂₆H₄₅IO₅Si₂	详情	详情
(XII)	55495	(6R)-6-{(1E,3R,4R,6R,7Z)-6-{[tert-butyl(dimethyl)silyl]oxy}-4-hydroxy-8-iodo-3-methyl-3-[(triethylsilyl)oxy]-1,7-octadienyl}-5,6-dihydro-2H-pyran-2-one		C₂₆H₄₇IO₅Si₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(XXVII)

The hydrolysis of the acetonide group of (XXIII) with HCl in aqueous methanol gives the dihydroxy compound (XXIV), which is monosilylated with Tbdms-OTf to yield compound (XXV). Further silylation of (XXV) with Tes-OTf affords the fully silylated compound (XXVI), which is selectively monodesilylated by means of HCl in aqueous THF/acetonitrile to provide the secondary alcohol (XXVII). Finally, this compound is condensed with the tributyltin derivative (XXVIII) by means of PdCl2(ACN)2 in DMF to furnish the target dihydropyranone intermediate (see Scheme no. 09093803b, intermediate (XXII).

参考文献中间体

合成目标

【1】 Fujii, K.; Maki, K.; Kanai, M.; Shibasaki, M.; Formal catalytic asymmetric total synthesis of fostriecin. Org Lett 2003, 5, 5, 733.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XXIII)	61557	(6R)-6-{(E)-2-[(4R,5R)-5-((2R,3Z)-2-{[tert-butyl(dimethyl)silyl]oxy}-4-iodo-3-butenyl)-2,2,4-trimethyl-1,3-dioxolan-4-yl]ethenyl}-5,6-dihydro-2H-pyran-2-one	C₂₃H₃₇IO₅Si	详情	详情
(XXIV)	61558	(6R)-6-((1E,3R,4R,6R,7Z)-6-{[tert-butyl(dimethyl)silyl]oxy}-3,4-dihydroxy-8-iodo-3-methyl-1,7-octadienyl)-5,6-dihydro-2H-pyran-2-one	C₂₀H₃₃IO₅Si	详情	详情
(XXV)	61559	(6R)-6-((1E,3R,4R,6R,7Z)-4,6-bis{[tert-butyl(dimethyl)silyl]oxy}-3-hydroxy-8-iodo-3-methyl-1,7-octadienyl)-5,6-dihydro-2H-pyran-2-one	C₂₆H₄₇IO₅Si₂	详情	详情
(XXVI)	51560	[(4S)-4-benzyl-5,5-dimethyl-2-oxo-1,3-oxazolidin-3-yl]lithium	C₁₂H₁₄LiNO₂	详情	详情
(XXVII)	55495	(6R)-6-{(1E,3R,4R,6R,7Z)-6-{[tert-butyl(dimethyl)silyl]oxy}-4-hydroxy-8-iodo-3-methyl-3-[(triethylsilyl)oxy]-1,7-octadienyl}-5,6-dihydro-2H-pyran-2-one	C₂₆H₄₇IO₅Si₂	详情	详情
(XXVIII)	61561	tert-butyl(diphenyl)silyl (2E,4Z)-5-(tributylstannyl)-2,4-pentadienyl ether; tert-butyl(diphenyl){[(2E,4Z)-5-(tributylstannyl)-2,4-pentadienyl]oxy}silane	C₃₃H₅₂OSiSn	详情	详情

Extended Information