(4-[(2R,3S,4R)-6-iodo-3-methyl-4-[(triisopropylsilyl)oxy]-3,4-dihydro-2H-pyran-2-yl]butoxy)(triisopropyl)silane; (2R,3S,4R)-6-iodo-3-methyl-2-[4-[(triisopropylsilyl)oxy]butyl]-3,4-dihydro-2H-pyran-4-yl triisopropylsilyl ether -Drug Synthesis Database

【结构式】

【分子编号】42424

【品名】(4-[(2R,3S,4R)-6-iodo-3-methyl-4-[(triisopropylsilyl)oxy]-3,4-dihydro-2H-pyran-2-yl]butoxy)(triisopropyl)silane; (2R,3S,4R)-6-iodo-3-methyl-2-[4-[(triisopropylsilyl)oxy]butyl]-3,4-dihydro-2H-pyran-4-yl triisopropylsilyl ether

【CA登记号】

【分子式】C₂₈H₅₇IO₃Si₂

【分子量】624.83425

【元素组成】C 53.82% H 9.19% I 20.31% O 7.68% Si 8.99%

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：(LXIII)

Synthesis of intermediate (LXIII): The reaction of aldehyde (LVI) with (-)-diisopinocampheyl-(E)-crotyl boronate (DIPCB) in toluene gives the chiral alcohol (LVII), which is protected with Bn-Br and NaH, yielding the benzyl ether (LVIII).The oxidation of the terminal double bond of (LVIII) with OsO4 and NaIO4 in THF/methanol/water affords the aldehyde (LIX), which is treated with (R,R)-diisopropyl allyl boronate (DISAB) to provide the allylic alcohol (LX). The silylation of (LX) with Tips-OTf, followed by debenzylation with Li/NH3 gives the secondary alcohol (LXI). The oxidation of the terminal double bond of (LXI) with OsO4 and NaIO4, with simultaneous cyclization yields the dihydropyran derivative (LXII), which is finally iodinated with n-BuLi, Bu3Sn-Cl and N-iodosuccinimide (NIS) in THF to afford the desired iodinate dihydropyran intermediate (LXIII).

参考文献中间体

合成目标

【1】 Hayward, M.M.; et al.; Total synthesis of altohyrtin A (spongistatin 1): Part 2. Angew Chem. Int Ed Engl 1998, 37, 1-2, 192.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(LVI)	42417	5-[(triisopropylsilyl)oxy]pentanal	C₁₄H₃₀O₂Si	详情	详情
(LVII)	42418	(3R,4R)-3-methyl-8-[(triisopropylsilyl)oxy]-1-octen-4-ol	C₁₈H₃₈O₂Si	详情	详情
(LVIII)	42419	[[(5R,6R)-5-(benzyloxy)-6-methyl-7-octenyl]oxy](triisopropyl)silane; benzyl (1R,2R)-2-methyl-1-[4-[(triisopropylsilyl)oxy]butyl]-3-butenyl ether	C₂₅H₄₄O₂Si	详情	详情
(LIX)	42420	(2S,3R)-3-(benzyloxy)-2-methyl-7-[(triisopropylsilyl)oxy]heptanal	C₂₄H₄₂O₃Si	详情	详情
(LX)	42421	(4S,5R,6R)-6-(benzyloxy)-5-methyl-10-[(triisopropylsilyl)oxy]-1-decen-4-ol	C₂₇H₄₈O₃Si	详情	详情
(LXI)	42422	benzyl (1R,2S,3S)-2-methyl-3-[(triisopropylsilyl)oxy]-1-[4-[(triisopropylsilyl)oxy]butyl]-5-hexenyl ether; (5S,6S,7R)-5-allyl-7-(benzyloxy)-3,3,13,13-tetraisopropyl-2,6,14-trimethyl-4,12-dioxa-3,13-disilapentadecane	C₃₆H₆₈O₃Si₂	详情	详情
(LXII)	42423	triisopropyl(4-[(2R,3S,4R)-3-methyl-4-[(triisopropylsilyl)oxy]-3,4-dihydro-2H-pyran-2-yl]butoxy)silane; (2R,3S,4R)-3-methyl-2-[4-[(triisopropylsilyl)oxy]butyl]-3,4-dihydro-2H-pyran-4-yl triisopropylsilyl ether	C₂₈H₅₈O₃Si₂	详情	详情
(LXIII)	42424	(4-[(2R,3S,4R)-6-iodo-3-methyl-4-[(triisopropylsilyl)oxy]-3,4-dihydro-2H-pyran-2-yl]butoxy)(triisopropyl)silane; (2R,3S,4R)-6-iodo-3-methyl-2-[4-[(triisopropylsilyl)oxy]butyl]-3,4-dihydro-2H-pyran-4-yl triisopropylsilyl ether	C₂₈H₅₇IO₃Si₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(LXIII)

Synthesis of intermediate (LXXXV): The condensation of aldehyde intermediate (LXXX) with iododihydropyran (LXIII) by means of n-BuLi in ethyl ether gives the adduct (LXXXI), which is methoxylated with NIS, HC(OMe)3, Bu3SnH and AIBN, yielding the intermediate (LXXXII). Desilylation of (LXXXII) with TBAF and resilylation with TBDMSCl and imidazole to afford silylated (LXXXIII) now switch the Tips groups of (LXXXII) to the more labile Tbdms groups. The selective desilylation of the primary Tbdms group of (LXXXIII) with HF in pyridine/methanol gives the butanol derivative (LXXXIV), which is treated successively with Ts2O, NaI and finally with PPh3 and DIEA in hot acetonitrile/methanol to yield the desired phosphonium iodide intermediate (LXXXV).

参考文献中间体

合成目标

【1】 Hayward, M.M.; et al.; Total synthesis of altohyrtin A (spongistatin 1): Part 2. Angew Chem. Int Ed Engl 1998, 37, 1-2, 192.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(LXIII)	42424	(4-[(2R,3S,4R)-6-iodo-3-methyl-4-[(triisopropylsilyl)oxy]-3,4-dihydro-2H-pyran-2-yl]butoxy)(triisopropyl)silane; (2R,3S,4R)-6-iodo-3-methyl-2-[4-[(triisopropylsilyl)oxy]butyl]-3,4-dihydro-2H-pyran-4-yl triisopropylsilyl ether	C₂₈H₅₇IO₃Si₂	详情	详情
(LXXX)	42440	(2R,3R,4R,5S,6R)-6-[(4S,5E)-7-chloro-2-methylene-4-[(triisopropylsilyl)oxy]-5,7-octadienyl]-4,5-bis[(4-methoxybenzyl)oxy]-3-methyltetrahydro-2H-pyran-2-carbaldehyde	C₄₁H₅₉ClO₇Si	详情	详情
(LXXXI)	42441	(S)-[(2R,3R,4R,5S,6R)-6-[(4S,5E)-7-chloro-2-methylene-4-[(triisopropylsilyl)oxy]-5,7-octadienyl]-4,5-bis[(4-methoxybenzyl)oxy]-3-methyltetrahydro-2H-pyran-2-yl]((2R,3S,4R)-3-methyl-4-[(triisopropylsilyl)oxy]-2-[4-[(triisopropylsilyl)oxy]butyl]-3,4-d	C₆₉H₁₁₇ClO₁₀Si₃	详情	详情
(LXXXII)	42442	(S)-[(2R,3R,4R,5S,6R)-6-[(4S,5E)-7-chloro-2-methylene-4-[(triisopropylsilyl)oxy]-5,7-octadienyl]-4,5-bis[(4-methoxybenzyl)oxy]-3-methyltetrahydro-2H-pyran-2-yl]((2R,4S,5S,6R)-2-methoxy-5-methyl-4-[(triisopropylsilyl)oxy]-6-[4-[(triisopropylsilyl)oxy	C₇₀H₁₂₁ClO₁₁Si₃	详情	详情
(LXXXIII)	42443	(S)-[(2R,4S,5S,6R)-4-[[tert-butyl(dimethyl)silyl]oxy]-6-(4-[[tert-butyl(dimethyl)silyl]oxy]butyl)-2-methoxy-5-methyltetrahydro-2H-pyran-2-yl][(2R,3R,4R,5S,6R)-6-((4S,5E)-4-[[tert-butyl(dimethyl)silyl]oxy]-7-chloro-2-methylene-5,7-octadienyl)-4,5-bis	C₆₁H₁₀₃ClO₁₁Si₃	详情	详情
(LXXXIV)	42444	4-[(2R,3S,4S,6R)-4-[[tert-butyl(dimethyl)silyl]oxy]-6-[(S)-[(2R,3R,4R,5S,6R)-6-((4S,5E)-4-[[tert-butyl(dimethyl)silyl]oxy]-7-chloro-2-methylene-5,7-octadienyl)-4,5-bis[(4-methoxybenzyl)oxy]-3-methyltetrahydro-2H-pyran-2-yl](hydroxy)methyl]-6-methoxy	C₅₅H₈₉ClO₁₁Si₂	详情	详情
(LXXXV)	42445	(4-[(2R,3S,4S,6R)-4-[[tert-butyl(dimethyl)silyl]oxy]-6-[(S)-[(2R,3R,4R,5S,6R)-6-((4S,5E)-4-[[tert-butyl(dimethyl)silyl]oxy]-7-chloro-2-methylene-5,7-octadienyl)-4,5-bis[(4-methoxybenzyl)oxy]-3-methyltetrahydro-2H-pyran-2-yl](hydroxy)methyl]-6-methox	C₇₃H₁₀₃ClIO₁₀PSi₂	详情	详情

Extended Information