Studies on the synthesis of bafilomycin A(1): stereochemical aspects of the fragment assembly aldol reaction for construction of the C(13)-C25) segment.
Studies on the synthesis of bafilomycin A(1): stereochemical aspects of the fragment assembly aldol reaction for construction of the C(13)-C25) segment.
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DOI：
10.1021/jo016413f
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发表时间：
2002-05
期刊：
影响因子：
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通讯作者：
W. Roush;T. Bannister;M. Wendt;J. A. Jablonowski;K. Scheidt
中科院分区：
文献类型：
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作者：
W. Roush;T. Bannister;M. Wendt;J. A. Jablonowski;K. Scheidt
通过手性醛6a与手性甲基酮7的片断组装Aldol反应，合成了与巴菲霉素A(1)的C(13)-C(25)区段相对应的高立体选择性的醇醇8a-c。手性醛片段的C(23)-OH的保护基也影响锂的烯醇酸-羟醛反应的选择性。相反，6a的Aldol反应和7a，c的氯化钛烯醇酸盐对C(15)-羟基保护基团的性质的敏感性要低得多。研究了手性醛与Takai的γ-甲氧基烯丙基铬试剂40的反应。这些反应的立体选择性也高度依赖于手性醛底物的保护基团和立体化学。
Highly stereoselective syntheses of aldols 8a-c corresponding to the C(13)-C(25) segment of bafilomycin A(1) were developed by routes involving fragment assembly aldol reactions of chiral aldehyde 6a and the chiral methyl ketones 7. A remote chelation effect plays a critical role in determining the stereoselectivity of the key aldol coupling of 6a and the lithium enolate of 7b. The protecting group for C(23)-OH of the chiral aldehyde fragment also influences the selectivity of the lithium enolate aldol reaction. In contrast, the aldol reaction of 6a and the chlorotitanium enolates of 7a,c were much less sensitive to the nature of the C(15)-hydroxyl protecting group. Studies of the reactions of chiral aldehydes with Takai's (gamma-methoxyallyl)chromium reagent 40 are also described. The stereoselectivity of these reactions is also highly dependent on the protecting groups and stereochemistry of the chiral aldehyde substrates.