66(P42) 光学活性4,5-Epoxy-(2E)-hexenoateの合成と天然物合成への利用(ポスター発表の部)
スポンサーリンク
概要
- 論文の詳細を見る
The anthracycline anti-biotics daunomycin and adriamycin are highly effective in the treatment of childhood leukemia and several types of solid tumor, and possess an amino sugar moiety, called L-daunosamine. Changing L-daunosamine of adriamycin with its 4-epimer, L-acosamine was reported to suppress the cardiotoxicity while retaining the anti-tumor activity. Based on the above report, we first focused on preparations of (4R,5R)-epoxy-(2E)-hexenoate 1 and (4R,5S)-epoxy-(2E)-hexenoate 2 because of being useful chiral synthons. The highly stereoselective syntheses of each of the four stereoisomers of (4,5)-epoxy-(2E)-hexenoate (>99%ee) ((4S,5S)-3, (4R,5R)-3, (4S,5R)-11, (4R,5S)-11) based on a chemoenzymatic chiral induction were achieved from the achiral precursor, methyl sorbate (Chart 4). For the syntheses of the target amino sugars from (4S,5S)-3, two synthetic routes are considerable. One is the 1,4-addition of benzylamine to the α,β-unsaturated ester after epoxy ring opening of (4S,5S)-3 by oxygen nucleophile such as benzylalcohol. The other is the direct 1,4-addition of benzylamine to the (4S,5S)-3 and subsequent regioselective cleavage of epoxy ring with intramolecular nucleophilic attack by ester carbonyl group (Chart 4). Methyl(4R,5S)-4,5-(isopropyridenedioxy)-(2E)-hexenoate (14) (>99%ee) was prepared from (4S,5S)-3 through two processes and subjected to a conjugated addition of benzylamine to give (3S,4R,5S)-15 with high diastereoselectivity. The subsequent lactonization under acidic condition proceeded formally to the total syntheses of L-daunosamine and L-acosamine (>99%ee) (Chart 6). On the other hand, direct conjugated addition of benzylamine to (4S,5S)-3 and the subsequent intramolecular lactonozation in the presence of trifluoromethanesulfonic acid led to the formal total syntheses of D-acosamine and D-ristosamine (>99%ee) (Chart 7). In conclusion, the syntheses of L-amino sugar such as L-daunosamine and L-acosamine and D-amino sugar such as D-acosamine and D-ristosamine were found to be distinguishable by changing the addition order of nucleophile against optically pure (4S,5S)-3.
- 天然有機化合物討論会の論文
- 1997-07-20
著者
-
尾能 満智子
東邦大薬
-
秋田 弘幸
東邦大薬
-
尾能 満智子
School Of Pharmaceutical Sciences Toho University
-
早乙女 周子
東邦大薬
-
秋田 弘幸
東邦大学薬学部
関連論文
- 107(P-30) Macrosphelide (+)-A,(-)-A,(+)-Eの全合成(ポスター発表の部)
- トリステアリンの結晶多形現象 : 構造と運動性との相関(結晶多形シンポジウムII)
- 53(P15) リパーゼによる構造異性体の分離を基盤とした(-)-Anisomycin,(+)-Elvirolの合成(ポスター発表の部)
- 66(P42) 光学活性4,5-Epoxy-(2E)-hexenoateの合成と天然物合成への利用(ポスター発表の部)
- Reaction of Methyl 4,5-Epoxy-(2E)-pentenoate with Arenes. II. Application to the Synthesis of (±)-Curcudiol, (±)-Curcuphenol, (±)-Curcuhydroquinone, and (±)-Curcuquinone
- P-22 酵素機能を利用する高立体選択的キラルシントンの合成とその天然物合成への応用(ポスター発表の部)
- Reaction of Methyl 4,5-Epoxy-(2E)-pentenoate with Arenes. I. A Facile Synthesis of 4-Aryl-5-hydroxy-(2E)-pentenoate Derivatives
- P-40 加水分解酵素の物質変換機能を基盤とする生理活性を有するデカリン型テルペン類の合成(ポスター発表の部)
- ウサギ肝臓カルボニル還元酵素のアセトヘキサミドおよび4-アセチルピリジン誘導体に対する諸性質(発表論文抄録(1994))
- 生体触媒による物質変換を基盤とした天然物合成
- Amidines. VIII. A Kinetic Study of Alcoholysis of N^1-Arenesulfonyl-N^1,N^2-diarylacetamidines
- Amidines. VII. : Hydrolysis and Alcoholysis of Carboxamides under Mild Conditions
- Amidines. VI. : 1,3-N, N-Acylotropic Amidine Rearrangement of N^1-Acyl Derivatives of N^1,N^2-Disubstituted Amidine
- Amidines. V. : Smiles Rearrangement of N^1-(p-Nitrobenzenesulfonyl)-N^1,N^2-diarylacetamidines
- Amidines. IV. : Hydrolysis of N^1-Acyl Derivatives of N^1,N^2-Diarylamidine in Carboxylate Buffer Solution
- Amidines. III. : A Kinetic Study of Acid Hydrolysis of Unsymmetrical N^1,N^2-Disubstituted Amidines
- Amidines.II. : Preparation of Unsymmetrical N^1,N^2-Disubstituted Amidines
- Amidines. I. Hydrolysis of N^1-Acyl- and N^1-Tosyl-N^1,N^2-diarylamidines
- A Kinetic Study of Alkaline Hydrolysis of 1-Arylamino-3-arylimino-1-butene
- A Kinetic Study of Alkaline Hydrolysis of β-Arylaminoacrolein
- A Kinetic Study of Cyclodehydration of β-Arylaminocroton-aldehyde Derivatives
- Preparation and Cyclodehydration of β-Arylaminocrotonaldehyde
- THE PREPARATION OF 14-HYDROXYLATED YOHIMBINE AND RESERPINE DERIVATIVES
- Preparation of 3-Substituted Quinolines. I. Alkylation of Malonaldehyde Dianil Derivatives
- Hydrolysis of Acyl Derivatives of N^1,N^2-Diarylamidine. I
- A Kinetic Study of Hydrolysis of β-Arylaminoacrolein Derivatives
- Reaction of β-Ethoxyacrolein and p-Toluidine in Benzene Solution
- Hydrolysis of Acyl Derivatives of Malonaldehyde Dianil. IV. Preparation of β-(p-Toluidino) crotonaldehyde
- Hydrolysis of Acyl Derivatives of Malonaldehyde Dianil. III
- Hydrolysis of Acyl Derivatives of Malonaldehyde Dianil. II. Aminolysis and Alcoholysis of Acyl Derivatives of Malonaldehyde Dianil and β-Arylaminoacrolein
- 89(P-14) Bithiazole及びβ-methoxyacrylate構造を有する抗生物質,cystothiazole類及びmelithiazole類の合成(ポスター発表の部)
- 末端アセチレンの分子内オキシ-カルボニル化反応 : 不斉触媒化およびタンデム型反応への応用
- P-60 簡便なCystothiazole A,C,D及びMelithiazol Bの全合成(ポスター発表の部)
- 加水分解酵素による物質変換を基盤とした天然物合成
- P-39 固定化β-glucosidaseとパラジウム触媒の組み合わせによる天然配糖体の合成(ポスター発表の部)
- 酵素反応を基盤とした有機合成
- 114(P50) 酵素化学的手法を基盤とするNikkomycin Bの合成(ポスター発表の部)
- リパーゼを用いる光学活性ヒドロキシエステルの創製とその生理活性化合物合成への応用 : ベンツリシジンA, Bアグリコンの全合成
- Hydrolysis of Acyl Derivatives of Malonaldehyde Dianil. I
- Hydrolysis of Malonaldehyde Dianil and β-Arylaminoacrolein Derivatives
- Reaction of Heterocyclic Amino Compound with Malonaldehyde Derivatives
- P-7 不斉環化-カルボニル化反応を利用した(+)-Bakkenolide Aの全合成(ポスター発表の部)