29 (-)-CP-263,114 (Phomoidride B)の全合成(口頭発表の部)
スポンサーリンク
概要
- 論文の詳細を見る
In 1997 CP-263,114 (Phomoidride B, 1) was isolated from the culture broth of an unidentified fungus by a Pfizer group and shown to inhibit squalene synthase as well as ras farnesyl transferase. In addition, CP-263,114 has a unique, densely functionalized polycyclic skeleton that consists of a bridgehead double bond, a γ-lactone-acetal, and a maleic anhydride moiety. These structural features and interesting bioactivities have attracted much interest from synthetic chemists. Herein we report a stereoselective total synthesis of 1. As illustrated in our retrosynthetic analysis of CP-263,114, we planned to construct the basic skeleton A (bicyclo[4.3.1]decene) by means of intramolecular Diels-Alder reaction. The precursor of Diels-Alder reaction could be prepared from three units; an aldehyde unit B, an acryloyl derivative, and a 1,3-diene unit C. The 1,3-diene unit 7 was synthesized by 1,4-addition reaction of alkenyl copper reagent 5 to the reactive allenic ester 3, followed by an introduction of one more methoxycarbonyl group. On the other hand, the aldehyde unit 13 was prepared from (S)-epichlorohydrin in a 11-step sequence. After the assembly of 7 and 13, boron-mediated diastereoselective aldol reaction, and subsequent Parikh-Doering oxidation afforded the enone 15. An intramolecular Diels-Alder reaction was performed by treatment of 15 with ZnCl_2・OEt_2 in the presence of a small amount of pyridine. After the construction of the bicyclic system, a novel protocol for the formation of the thiomaleic anhydride 20 via thiobutenolide 19 was employed. Finally homologation of the ester and subsequent acid-promoted formation of γ-lactone-acetal 23 were achieved to complete the total sythesis of (-)-CP-263,114 (1). The synthetic 1 was identical in all respects with the natural CP-263,114 [^1H NMR, ^<13>C NMR, HRMS and [α]_D ?10°(c = 0.25, CH_2Cl_2) (lit. [α]_D ?11°(c = 0.5, CH_2Cl_2))]. Accordingly, the absolute configuration of CP-263,114 should be the one depicted in the last scheme.
- 天然有機化合物討論会の論文
- 2000-10-01
著者
関連論文
- 20 (-)-セロトベニンの全合成(口頭発表の部)
- 11 ロイストロダクシンBの全合成(口頭発表の部)
- 29 (-)-CP-263,114 (Phomoidride B)の全合成(口頭発表の部)
- 43 インドロカルバゾール(+)-K252aの合成研究(口頭発表の部)
- 6 ゲルセミンの合成研究(口頭発表の部)
- 11 レイナマイシンの全合成(口頭発表の部)
- 32 Gliotoxin-Sporidesmin関連化合物の合成研究
- 18 テトロドトキシンおよび関連化合物の合成研究
- 28 (+)-ビンブラスチンの全合成(口頭発表の部)
- 16 エクチナサイジン743の全合成(口頭発表の部)
- 24 (-)-Conophyllineの全合成(口頭発表の部)
- 30 (+)-Yatakemycinの全合成(口頭発表の部)
- 36(D-6) (-)-ストリキニーネの全合成(口頭発表の部)
- 66(P-47) (+)-リゼルグ酸の合成研究(ポスター発表の部)
- 11 2-アルケニルチオアニリドのラジカル環化反応を用いた新規2,3-二置換インドール合成法とその応用(口頭発表の部)
- 13 アルテミシジンの合成研究(口頭発表の部)
- 39 Huperzine Aの全合成(口頭発表の部)
- 24 (+)-Haplophytineの全合成(口頭発表の部)
- P-11 (-)-サリノスポラミドAの全合成(ポスター発表の部)
- 32 Manzamine Aの合成研究(口頭発表の部)
- 22 アニサチンの全合成(口頭発表の部)