A divergent asymmetric approach to aza-spiropyran derivative and(1s,8aR)-1-hydroxyindolizidine

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	A divergent asymmetric approach to aza-spiropyran derivative and(1s,8aR)-1-hydroxyindolizidine
	Zheng, JF ; Chen, W ; Huang, SY ; Ye, JL ; Huang, PQ ; Huang PQ(黄培强)
刊名	http://dx.doi.org/10.1186/1860-5397-3-41
	2007-11-08
关键词	INDOLIZIDINE ALKALOIDS SLAFRAMINE QUINOLIZIDINE ALKALOIDS RHIZOCTONIA-LEGUMINICOLA PANDANUS-AMARYLLIFOLIUS NATURAL OCCURRENCE SWAINSONINE 1-HYDROXYINDOLIZIDINES BIOSYNTHESIS CHEMISTRY (+)-LENTIGINOSINE
英文摘要	Background: Spiroketals and the corresponding aza-spiroketals are the structural features found in a number of bioactive natural products, and in compounds possessing photochromic properties for use in the area of photochemical erasable memory, self-development photography, actinometry, displays, filters, lenses of variable optical density, and photomechanical biomaterials etc. And (1R, 8aS)-1-hydroxyindolizidine (3) has been postulated to be a biosynthetic precursor of hydroxylated indolizidines such as (+)- lentiginosine 1, (-)-2-epilentiginosine 2 and (-)- swainsonine, which are potentially useful antimetastasis drugs for the treatment of cancer. In continuation of a project aimed at the development of enantiomeric malimide-based synthetic methodology, we now report a divergent, concise and highly diastereoselective approach for the asymmetric syntheses of an aza-spiropyran derivative 7 and (1S, 8aR)-1-hydroxyindolizidine (ent-3). Results: The synthesis of aza-spiropyran 7 started from the Grignard addition of malimide 4. Treatment of the THP-protected 4-hydroxybutyl magnesium bromide with malimide 4 at -20 degrees C afforded N,O-acetal 5a as an epimeric mixture in a combined yield of 89%. Subjection of the diastereomeric mixture of N,O-acetal 5a to acidic conditions for 0.5 h resulted in the formation of the desired functionalized aza-spiropyran 7 as a single diastereomer in quantitative yield. The stereochemistry of the aza-spiropyran 7 was determined by NOESY experiment. For the synthesis of ent-3, aza-spiropyran 7, or more conveniently, N,O-acetal 5a, was converted to lactam 6a under standard reductive dehydroxylation conditions in 78% or 77% yield. Reduction of lactam 6a with borane-dimethylsulfide provided pyrrolidine 8 in 95% yield. Compound 8 was then converted to 1-hydroxyindolizidine ent-3 via a four-step procedure, namely, N-debenzylation/O-mesylation/Boc-cleavage/cyclization, and O-debenzylation. Alternatively, amino alcohol 8 was mesylated and the resultant mesylate 12 was subjected to hydrogenolytic conditions, which gave (1S, 8aR)- 1-hydroxyindolizidine (ent-3) in 60% overall yield from 8. Conclusion: By the reaction of functionalized Grignard reagent with protected (S)- malimide, either aza-spiropyran or (1S, 8aR)-1-hydroxyindolizidine skeleton could be constructed in a concise and selective manner. The results presented herein constitute an important extension of our malimide-based synthetic methodology.
语种	英语
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/64452]
专题	化学化工－已发表论文
推荐引用方式 GB/T 7714	Zheng, JF,Chen, W,Huang, SY,et al. A divergent asymmetric approach to aza-spiropyran derivative and(1s,8aR)-1-hydroxyindolizidine[J]. http://dx.doi.org/10.1186/1860-5397-3-41,2007.
APA	Zheng, JF,Chen, W,Huang, SY,Ye, JL,Huang, PQ,&黄培强.(2007).A divergent asymmetric approach to aza-spiropyran derivative and(1s,8aR)-1-hydroxyindolizidine.http://dx.doi.org/10.1186/1860-5397-3-41.
MLA	Zheng, JF,et al."A divergent asymmetric approach to aza-spiropyran derivative and(1s,8aR)-1-hydroxyindolizidine".http://dx.doi.org/10.1186/1860-5397-3-41 (2007).