Abstract
本論文共分三部份：第一部份為光學活性的2-矽氧基■喃55之不對稱 Diels-Alder 反應研究。以L-ascorbic acid(維他命C) 為起始物合成光 學活性的 2-矽氧基■喃55，然後研究其與DMAD 的不對稱Diels-Alder 的反應。我們發現當以(+)-Eu(hfc)3 為路易士酸時, 2-矽氧基■喃 55i 及55j 與有最好的非對映選擇性(9.3:1)。我們並且 X-ray 單晶繞射證明 加成產物的立體化學。第二部份是以天然物 Avermectin 之六氫苯駢■喃 部份為目標物的合成研究。首先以第一部份之研究結果所得到的不對稱 Diels-Alder 加成產物56j進行還原-開環反應研究。我們發現加成物56j 在Mg/CH3OH 還原後所得到化合物123，在路易士酸或者質子酸用下打開架 橋C-O 鍵得到化合物122，而在nBu4NF/THF 的反應條件作用下會打開C-C 鍵得到化合物124。 接下來，為了合成上的考慮，加成物的還原-開環產 物有去羧反應(decarboxylation)的困難，於是研究以氧化態異原子為親 二烯拉電子基之不對稱Diels-Alder 反應，3-硝基丙烯酸甲酯(methyl 3-nitroacrylate)145及 3-苯磺醯基丙炔酸乙酯(ethyl 3-phenylsufonylpropiolate)150。另外以OsO4/NMO作用 Diels-Alder加 成產物67b得到同向雙羥化後再開環的產物160。 第三部份的研究以 taxol 的C,D 環為目標，不對稱Diels-Alder加成物67b經 Mg/CH3OH 還原 後進行碘內酯化反應(iodolactonization) 得到的產物220， 再經Bu3SnH 還原，水解相鄰雙醇的保護基再以四醋酸鉛氧化斷裂去除一個碳數，得到 合成taxol 的C,D 環的重要中間體228。 The thesis consists of five chapters. The first chapter describes a detailed study of asymmetric Diels-Alder reaction of chiral 2-siloxyfurans. The required chiral 2-siloxyfurans 55 were synthesized from L-ascorbic acid (vitamin C). The compound 55 when treatment with dimethyl acentylenedicarboxylate at room temperature: underwent a facile Diels-Alder reaction. A very good diastereoselectivity of 9.3 : 1 was obtained when (+)-Eu(hfc)3 was used as catalyst for this reaction. The stereochemistry of the Diels-Alder adduct was determined by the X-ray single crystal analysis. The second chapter describes a novel approach for the synthesis of hexahydrobenzofuran subunit of nature product avermectin. In this approach, the starting material ie. the Diels-Alder adduct 56j was synthesized as disclosed in the previous chapter. Treatment of the cycloadduct 56j with magnesium and methanol gave the reduced product 123. The compound 123 when treated with zinc bromide (Lewis acid) resulted a cyclohexenone derivative 122. On the other hand, the reaction of 123 with tetrabutylammonium fluoride gave the enelactone 124. A study of the Diels-Alder reaction of 2-siloxyfurans with two more dienophiles viz. methyl 3-nitro- acrylate 145 and ethyl 3-phenylsulfonylpropiolate 150 were also present in this chapter. However compound 66b on oxidation with osmium tetroxide/N-methyl morpholine N-oxide underwent dihydroxylation followed by ring-opening reaction to achieve the product 160. The third chapter deals with a new approach toward the synthesis of the C, D-ring of taxol. The reduction product of the Diels-Alder adduct 66b underwent iodolactonization to give the lactone 220. The reduction of iodolactone 220 with tribuyltinhydride and subsequent hydrolysis of protecting group of vicinal diol was carried out, which on oxidative cleavage with lead tetraacetate followed by reduction with sodium borohydride afforded the synthetic intermediate 228 of the taxol C, D-ring.