(2R,3R,4S)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyltetradecanal -Drug Synthesis Database

【结构式】

【分子编号】47171

【品名】(2R,3R,4S)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyltetradecanal

【CA登记号】

【分子式】C₂₄H₄₀O₃

【分子量】376.5798

【元素组成】C 76.55% H 10.71% O 12.75%

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：(XVII)

The condensation of decanal (I) with silyl enol ether (II) by means of a chiral catalyst and Sn(OTf)2 in dichloromethane gives the chiral thiocarboxylic ester (III), which is treated with chlorothioformate (IV) and pyridine in refluxing dichloroethane to yield the thiocarbonic ester (V). The reduction of (V) with Bu3SnH and AIBN in refluxing toluene affords the chiral thioester (VI), which is reduced with LiAlH4 in THF to provide the alcohol (VII). The oxidation of (VII) with oxalyl chloride in DMSO/dichloromethane gives the corresponding aldehyde (VIII), which is condensed with phosphorane (IX) to yield the unsaturated ester (X). The reduction of the ester group of (X) with DIBAL in dichloromethane affords the allyl alcohol (XI), which is submitted to a Sharpless epoxidation with tert-butyl hydroperoxide (TBHP) and Ti(O-iPr)4 in the presence of diethyl D-tartrate, providing the chiral epoxide (XII). Methylation of the epoxide ring of (XII) with MeLi and CuI in ethyl ether gives the diol (XIII), which is treated with the dimethyl acetal (XIV) and Ts-OH in dichloromethane to yield the 1,3-dioxane (XV). The reductive cleavage of (XV) with DIBAL in the same solvent affords the Pmb ether (XVI), whose primary alcohol is oxidized with oxalyl chloride in DMSO/dichloromethane to provide the aldehyde (XVII). The condensation of (XVII) with phosphorane (XVIII) in refluxing THF gives the unsaturated ester (XIX).

参考文献中间体

合成目标

【1】 Wakabayashi, T.; Mori, K.; Kobayashi, S.; Total synthesis and structural elucidation of khafrefungin. J Am Chem Soc 2001, 123, 7, 1372.

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)	31059	decanal	112-31-2	C₁₀H₂₀O	详情	详情
(II)	47158	(Z)-1-(propylsulfanyl)-1-propenyl trimethylsilyl ether; trimethyl[[(Z)-1-(propylsulfanyl)-1-propenyl]oxy]silane		C₉H₂₀OSSi	详情	详情
(III)	47159	S-propyl (2S,3R)-3-hydroxy-2-methyldodecanethioate		C₁₆H₃₂O₂S	详情	详情
(IV)	25805	1-[(chlorocarbothioyl)oxy]benzene; Phenylchlorothioformate	1005-56-7	C₇H₅ClOS	详情	详情
(V)	47160	S-propyl (2S,3R)-2-methyl-3-[(phenoxycarbothioyl)oxy]dodecanethioate		C₂₃H₃₆O₃S₂	详情	详情
(VI)	47161	S-propyl (2S)-2-methyldodecanethioate		C₁₆H₃₂OS	详情	详情
(VII)	47162	(2S)-2-methyl-1-dodecanol		C₁₃H₂₈O	详情	详情
(VIII)	47163	(2S)-2-methyldodecanal		C₁₃H₂₆O	详情	详情
(IX)	47164	propyl 2-(triphenylphosphoranylidene)acetate		C₂₃H₂₃O₂P	详情	详情
(X)	47165	propyl (E,4S)-4-methyl-2-tetradecenoate		C₁₈H₃₄O₂	详情	详情
(XI)	47166	(E,4S)-4-methyl-2-tetradecen-1-ol		C₁₅H₃₀O	详情	详情
(XII)	47167	[(2S,3R)-3-[(1S)-1-methylundecyl]oxiranyl]methanol		C₁₅H₃₀O₂	详情	详情
(XIII)	47168	(2S,3R,4S)-2,4-dimethyl-1,3-tetradecanediol		C₁₆H₃₄O₂	详情	详情
(XIV)	26485	1-(dimethoxymethyl)-4-methoxybenzene	2186-92-7	C₁₀H₁₄O₃	详情	详情
(XV)	47169	(4R,5S)-2-(4-methoxyphenyl)-5-methyl-4-[(1S)-1-methylundecyl]-1,3-dioxane; methyl 4-[(4R,5S)-5-methyl-4-[(1S)-1-methylundecyl]-1,3-dioxan-2-yl]phenyl ether		C₂₄H₄₀O₃	详情	详情
(XVI)	47170	(2S,3R,4S)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-1-tetradecanol		C₂₄H₄₂O₃	详情	详情
(XVII)	47171	(2R,3R,4S)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyltetradecanal		C₂₄H₄₀O₃	详情	详情
(XVIII)	47172	propyl 2-(triphenylphosphoranylidene)propanoate		C₂₄H₂₅O₂P	详情	详情
(XIX)	47173	propyl (E,4S,5R,6S)-5-[(4-methoxybenzyl)oxy]-2,4,6-trimethyl-2-hexadecenoate		C₃₀H₅₀O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XII)

Alkenylboronic acid (XV): The intermediate tetradecyl aldehyde derivative (XII) has been obtained by an already reported sequence (see scheme no. 23979101a, intermediates (I) to (XVII)) starting from decanal (XI). The reaction of aldehyde (XII) with CBr4 and PPh3 in dichloromethane gives the dibromovinyl derivative (XIII), which is treated with BuLi and Me-I in THF to yield the alkyne (XIV). Finally, this compound is condensed with catecholborane to provide the target alkenylboronic acid (XV).

参考文献中间体

合成目标

【1】 Kobayashi, S.; Mori, K.; Wakabayashi, T.; Yasuda, S.; Hanada, K.; Convergent total synthesis of khafrefungin and its inhibitory activity of fungal sphigolipid syntheses. J Org Chem 2001, 66, 16, 5580.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XI)	31059	decanal	112-31-2	C₁₀H₂₀O	详情	详情
(XII)	47171	(2R,3R,4S)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyltetradecanal		C₂₄H₄₀O₃	详情	详情
(XIII)	60341	1-({[4,4-dibromo-2-methyl-1-(1-methylundecyl)-3-butenyl]oxy}methyl)-4-(methyloxy)benzene; 4,4-dibromo-2-methyl-1-(1-methylundecyl)-3-butenyl [4-(methyloxy)phenyl]methyl ether		C₂₅H₄₀Br₂O₂	详情	详情
(XIV)	60342	1-({[2-methyl-1-(1-methylundecyl)-3-pentynyl]oxy}methyl)-4-(methyloxy)benzene; methyl 4-({[2-methyl-1-(1-methylundecyl)-3-pentynyl]oxy}methyl)phenyl ether		C₂₆H₄₂O₂	详情	详情
(XV)	60343	1,3,5-trimethyl-4-({[4-(methyloxy)phenyl]methyl}oxy)-1-pentadecenylboronic acid		C₂₆H₄₅BO₄	详情	详情

Extended Information