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    • 7. 发明申请
    • MANUFACTURE OF RETINOIDS
    • 生物制品的制造
    • WO2003037856A1
    • 2003-05-08
    • PCT/EP2002/011878
    • 2002-10-24
    • ROCHE VITAMINS AGRADSPIELER, AlexanderRUETTIMANN, August
    • RADSPIELER, AlexanderRUETTIMANN, August
    • C07C403/08
    • C07C403/14C07B2200/09C07C403/04C07C403/08C07C403/10C07C403/12C07C403/22C07C2601/16
    • A process for the manufacture of retinal (I) comprises reacting a 5-(2,6,6-trimethyl-cyclohex-1-enyl)-1,4-pentadiene derivative (IIa) or a 5-(2,6,6-trimethyl-cyclohex-2-enyl)-1,4-pentadiene derivative (IIb) or a 5-(2,6,6-trimethyl-2-cyclohexen-1-ylidene)-1-pentene derivative (IIc) or a 5-(2,6,6-trimethyl-cyclohex-1-enyl)-penta-1-en-4-yne derivative (IId) or a 5-(2,6,6-trimethyl-cyclohex-2-enyl)-penta-1-en-4-yne derivative (IIe) with a 1,3-butadiene derivative H 2 C=C(CH 3 )CCH=CHOR 4 (III) in the presence of a Lewis or Brönsted acid and subjecting the compound obtained in each case [(IVa), (IVb), (IVc), (IVd) or (IVe), respectively] to basic or acidic conditions to eliminate therefrom the moiety R 2 H and thus produce, according to the immediate precursor, retinal itself or a particular derivative thereof [(I'), (I''), (Va) or (Vb), respectively] and, where in two cases such derivative is produced featuring a triple bond [derivative (Va) or (Vb)], hydrogenating this to produce retinal (I) or the derivative (I'), respectively, and each case where a derivative (I') or (I'') has been produced, isomerizing this under basic or acidic conditions or in the presence of a metal catalyst to the desired retinal (I). The so-produced retinal is usually in the form of an isomeric mixture, normally as (9 E/Z, 13 E/Z)-retinal, and this can be isomerized according to a further inventive aspect to (all-E)-retinal by the acid-catalysed formation of an adduct of (all-E)-retinal with hydroquinone in crystalline form. The so obtained (all-E)-retinal-hydroquinone adduct can then if desired be converted to vitamin A alcohol in the predominantly (all-E)-isomeric form by a method known per se. The novel starting materials (IIa), (IIb), (IIc), (IVI) and (IIe) represent a still further inventive aspect. Retinal is a valuable intermediate in the synthesis of further vitamin A compounds (retinoids). The retinoids, particularly vitamin A alcohol (retinol), are known to be valuable substances which promote the well-being of humans, inter alia in respect of vision, the immune system and growth, and for this reason are often used as components of multivitamin preparations and as additives for certain food- and feedstuffs.
    • 制备视网膜(I)的方法包括使5-(2,6,6-三甲基 - 环己-1-烯基)-1,4-戊二烯衍生物(IIa)或5-(2,6,6 - 三甲基 - 环己-2-烯基)-1,4-戊二烯衍生物(IIb)或5-(2,6,6-三甲基-2-环己烯-1-亚基)-1-戊烯衍生物(IIc)或 5-(2,6,6-三甲基 - 环己-1-烯基) - 戊-1-烯-4-炔衍生物(IId)或5-(2,6,6-三甲基 - 环己-2-烯基) - 戊-1-烯-4-炔衍生物(IIe)与1,3-丁二烯衍生物H 2 C = C(CH 3)CCH = CHOR 4(III)在路易斯或布朗斯台德酸存在下反应, 分别得到[(IVa),(IVb),(IVc),(IVd)或(IVe)]至碱性或酸性条件,从而除去部分R 2 H,从而根据即时 前体,视黄醛本身或其特定衍生物[(I'),(I“),(Va)或(Vb)],并且在两种情况下,衍生物以三键[衍生物(Va) 或(Vb)],将其氢化以产生视网膜(I )或衍生物(I'),并且每种情况下已经生成衍生物(I')或(I“),在碱性或酸性条件下或在金属催化剂存在下使其异构化为所需的视黄醛 (一世)。 如此产生的视网膜通常为异构体混合物的形式,通常为(9E / Z,13E / Z) - 视网膜,并且其可以根据另外的发明方面异构化为(全E) - 视网膜 通过酸性催化形成(全E) - 视黄酸与氢醌的结晶形式的加合物。 如果需要,可以通过本身已知的方法将如此获得的(全E) - 视黄酸 - 氢醌加合物以主要(全E) - 异构体形式转化为维生素A醇。 新型起始原料(IIa),(IIb),(IIc),(IVI)和(IIe)代表又一发明方面。 视网膜是合成其他维生素A化合物(类视黄醇)的有价值的中间体。 维生素A,特别是维生素A酒精(视黄醇)已知是促进人类福祉的有价值物质,特别是在视力,免疫系统和生长方面,因此经常被用作多种维生素的组分 制剂和某些食品和饲料的添加剂。
    • 8. 发明申请
    • PRACTICAL SYNTHETIC METHOD OF RETINOID AND CAROTENOID COMPOUNDS
    • 反应物和卡诺菌素化合物的实用合成方法
    • WO2002092560A1
    • 2002-11-21
    • PCT/KR2002/000660
    • 2002-04-11
    • KOO, SanghoJEONG, Young, Cheol
    • KOO, SanghoJEONG, Young, Cheol
    • C07C403/08
    • C07C403/24C07C403/08C07C403/14C07C403/22C07C2601/16
    • The present invention relates to an effective and practical method for preparing retinol (Chemical Formula 2), retinal (Chemical Formula 3) and βcarotene (Chemical Formula 4) by using C-15 allylic disulfone compound (Chemical Formula 1) as an intermediate compound, that is prepared through a stable and economic process, for syntheses of retinoid and carotenoid compounds.According to the present invention, retinol (Chemical Formula 2), retinal (Chemical Formula 3) and β-carotene (Chemical Formula 4) are effectively prepared, via coupling reaction of carbanion that is obtained from deprotonation of the C-15 disulfone compound (Chemical Formula 1) by excess amount (2 equivalents or more) of base, with C-5 halo-acetate compound (A), C-5 halo-acetal compound (C) and C-10 dihaloallylic sulfide compound (F), respectively followed by dehydrosulfonation reaction.
    • 本发明涉及使用C-15烯丙基二砜化合物(化学式1)作为中间体化合物制备视黄醇(化学式2),视黄醛(化学式3)和β-胡萝卜素(化学式4)的有效和实用的方法 根据本发明,视黄醇(化学式2),视黄醛(化学式3)和β-胡萝卜素(化学式4)被有效地制备,可以通过稳定和经济的方法制备,用于合成类视色素和类胡萝卜素化合物。 通过过量(2当量或更多)碱的C-15二砜化合物(化学式1)的去质子化获得的碳负离子与C-5卤代乙酸酯化合物(A),C-5 卤代缩醛化合物(C)和C-10二卤代硫醚化合物(F),然后进行脱水磺化反应。