The Study of Chemical Synthesis for Crocins
|School||Sichuan Normal University|
|Keywords||chemical synthesis Wittig-Horner reaction crocetin-dimeathyleste crocetin crocins|
In this paper we describe an efficient seven-step synthesis of crocetin, which is the key intermediate for the synthesis of several carotenoids and other polyene natural, such as crocins.The synthesis stars by treatment of E-1, 4-dibrom-2-butene and triethylphosphit, according to Wittig-Horner reaction, to give the E-butene- （2）-diphosphon acid- （1,4）-tetraethylester , as a fleet tan oil with a 95% yield. E-butene- （2）-diphosphon acid- （1,4）-tetraethylester was submitted to next reaction processing with pyruvic aldehyde dimethyl acetal under nitrogen ,then added NaH to give the 2,7-Dimethyl- octatrien-（2,4,6）-dial, as a fleet yellow solid with a 71.12% yield.Another synthesis was performed by treatment of 1 equiv of trans-2, 3, -dimethylacrylic acid, 1 equiv of NBS and small amount of dibenzoyl peroxide to give trans-2-methyl-4-bromocrotonic acid with 90%. trans-2-methyl-4- bromocrotonic acid was reacted with excess methanol and thionyl chloride for 16 h to give methyl trans-2-methyl-4-bromocrotonate （methyl E-γ-bromotiglate） in 73.23% yield.The synthesis was carried on by treatment of methyl trans-2-methyl- 4-bromocrotonate （methyl E-γ-bromotiglate） and triethylphosphit, according to Wittig-Horner reaction, to give the methyl O,O-diethyl-γ- phosphonotiglate , as a fleet tan oil with a 94% yield. methyl O,O-diethyl-γ- phosphonotiglate was submitted to next reaction processing with 2,7-Dimethyl- octatrien-（2,4,6）-dial at 0℃under nitrogen, then added NaH to give the crocetin-dimeathylester, as a red solid with a 60.20% yield.A solution of crocetin-dimeathylester in methanol and THF[V∶V=2:3] was added to alkalic hydrolysis , at 50℃for 1h. The solid was removed by filtration and then was acidulated to give the crocetin in 91.2% yield; A solution of crocetin and N,N-Carbonyldiimidazole in DMSO at room temperature for 1h-2h to give crocetin-imidazole, as a red solid with a 95.8% yield. Crocetin-imidazole was submitted to next reaction processing with saccharides under nitrogen in a suspension of NaH of pyridine to give crocins , as a red solid with a 70.8% yield.The structure of crocetin-dimeathylester, crocetin, crocetin-imidazole and crocins were affirmed by 1HNMR spectra, 13CNMR spectra, UV and FT-IR spectroscopy. Therefore, the designing route of synthesis is feasible.