Title

一個簡潔的方法—由 D-來蘇醣合成出Phytosphingosine, Ceramide, α-Galactosylceramide 及其O-6 類似物

Translated Titles

A Concise Synthesis of Phytosphingosine, Ceramide, α-Galactosylceramide and O-6 Analogs. from D-Lyxose.

DOI

10.6845/NCHU.2013.00001

Authors

顏郁芬

Key Words

Phytosphingosine ; Ceramide ; α-Galactosylceramide ; Phytosphingosine ; Ceramide ; α-Galactosylceramide

PublicationName

中興大學化學系所學位論文

Volume or Term/Year and Month of Publication

2013年

Academic Degree Category

碩士

Advisor

羅順原

Content Language

繁體中文

Chinese Abstract

α-Galactosylceramides (α-GalCers)系列化合物因其具重要的免疫調節特性,在近幾年來受到關注,並有許多相關合成方法陸續被提出。我們以D-來蘇醣(D-lyxose)的二醇衍生物為起始物合成出α-GalCer分子,並利用共同中間體合成出phytosphingosine及ceramide,總共經由九步驟、七步驟及八步驟,產率分別為26%、20%及15%。接著我們更進一步地發展出更為精簡的合成步驟,總共只需五步便可由D-來蘇醣合成出α-GalCer,總產率32%,並將此法應用於其他相關衍生物之合成。縮短步驟的關鍵為以D-來蘇醣及醣基碘化物進行一鍋化保護─醣鏈結反應,並直接以順式之雙鍵化合物進行疊氮基─胺基轉換並生成醯胺化合物,最後再將所有保護基以一併去除得到目標物。

English Abstract

α-Galactosylceramides (α-GalCers) are well known as immunostimulating agents having therapeutic potential. In recent years, a wide variety of different synthetic strategies have been explored in optimising the synthesis of α-GalCers. In this thesis, the total synthesis of α-GalCer, phytosphingosine and ceramide through an α-galactosyl phytosphingosine derivative as a common synthon were accomplished in 26%, 20%, and 15% overall yields in nine, seven, and eight steps, respectively, from the acetonide-protected D-lyxose. Furthermore, we have developed a more concise synthesis of α-GalCer from D-lyxose in 32% overall yield just only in five steps, and expected to provide access to other structurally related glycolipids for exploring their immunostimulating activities and other biological properties. The short and efficient protocol involves a one-pot protection and glycosidation of D-lyxose with D-galactosyl iodide as a key step. The α-linked disaccharide so obtained was subsequently transformed into α-GalCer in four steps involving Z-selective Wittig olefination at C-1, stereo-inversion at C-4 using azide, one-pot reduction of azide and amidation, and global deprotection.

Topic Category 基礎與應用科學 > 化學
理學院 > 化學系所
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