A formal total synthesis of (+)-apicularen A: base-induced conversion of apicularen-derived intermediates into salicylihalamide-like products

被引:44
作者
Lewis, A
Stefanuti, I
Swain, SA
Smith, SA
Taylor, RJK [1 ]
机构
[1] Univ York, Dept Chem, York YO10 5DD, N Yorkshire, England
[2] GlaxoSmithKline, Med Res Ctr, Stevenage SG1 2NY, Herts, England
关键词
D O I
10.1039/b209637b
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
A synthesis of apicularen precursor (-)-6 in 18 steps from D-glucal is reported. As (+)-6 has been converted into the potent, naturally occurring salicylate anti-cancer agent, (-)-apicularen A in 8 steps, this study constitutes a formal total synthesis of (+)-apicularen A. Key steps in the synthetic route include: (i) Useful D-glucal elaboration processes, (ii) organometallic displacements at carbohydrate C-6 triflates using Knochel-type and related functionalised, aromatic Grignard reagents, (iii) stereoselective allyltrimethylsilane-acetal reactions generating C-allyl systems, (iv) stereocontrolled aldehyde allylation processes from both substrate and reagent, and (v) a novel Keck-type macrolactonisation. In addition, preliminary studies are reported in which a procedure has been devised to convert apicularen-derived intermediates into salicylihalamide-like products.
引用
收藏
页码:104 / 116
页数:13
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