Abstract
(Chemical Equation Presented) (-)-Merrilactone A [(-)-1], isolated from Illicium merrillianum in 2000, possesses neurite outgrowth activity in cultures of fetal rat cortical neurons, and, therefore, is expected to show therapeutic potential for the treatment of neurodegeneration associated with Alzheimer's and Parkinson's diseases. A part from its biological aspects, the caged pentacyclic skeleton of 1 poses interesting synthetic challenges. Here, we report the total synthesis of the unnatural enantiomer of merrilactone A [(+)-1], based on a novel desymmetrization strategy. The chiral lithium amide 16g promoted an enantioselective transannular aldol reaction of eight-membered meso-diketone 3d, establishing the absolute stereochemistries of four chiral centers of the cis-bicyclo[3.3.0]octane framework of 1 in a single step. The obtained compound 4d served as a platform for the subsequent functional group manipulations necessary for the construction of (+)-1. Surprisingly, both the natural and unnatural enantiomers of synthetic merrilactone A equally promoted neurite outgrowth in primary neuronal cultures.
| Original language | English |
|---|---|
| Pages (from-to) | 3065-3075 |
| Number of pages | 11 |
| Journal | Journal of Organic Chemistry |
| Volume | 72 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 2007 Apr 13 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Organic Chemistry
Cite this
Total synthesis and bioactivity of an unnatural enantiomer of merrilactone A : Development of an enantioselective desymmetrization strategy. / Inoue, Masayuki; Lee, Nayoung; Kasuya, Satoshi; Satou, Takaaki; Hirama, Masahiro; Moriyama, Miyako; Fukuyama, Yoshiyasu.
In: Journal of Organic Chemistry, Vol. 72, No. 8, 13.04.2007, p. 3065-3075.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Total synthesis and bioactivity of an unnatural enantiomer of merrilactone A
T2 - Development of an enantioselective desymmetrization strategy
AU - Inoue, Masayuki
AU - Lee, Nayoung
AU - Kasuya, Satoshi
AU - Satou, Takaaki
AU - Hirama, Masahiro
AU - Moriyama, Miyako
AU - Fukuyama, Yoshiyasu
PY - 2007/4/13
Y1 - 2007/4/13
N2 - (Chemical Equation Presented) (-)-Merrilactone A [(-)-1], isolated from Illicium merrillianum in 2000, possesses neurite outgrowth activity in cultures of fetal rat cortical neurons, and, therefore, is expected to show therapeutic potential for the treatment of neurodegeneration associated with Alzheimer's and Parkinson's diseases. A part from its biological aspects, the caged pentacyclic skeleton of 1 poses interesting synthetic challenges. Here, we report the total synthesis of the unnatural enantiomer of merrilactone A [(+)-1], based on a novel desymmetrization strategy. The chiral lithium amide 16g promoted an enantioselective transannular aldol reaction of eight-membered meso-diketone 3d, establishing the absolute stereochemistries of four chiral centers of the cis-bicyclo[3.3.0]octane framework of 1 in a single step. The obtained compound 4d served as a platform for the subsequent functional group manipulations necessary for the construction of (+)-1. Surprisingly, both the natural and unnatural enantiomers of synthetic merrilactone A equally promoted neurite outgrowth in primary neuronal cultures.
AB - (Chemical Equation Presented) (-)-Merrilactone A [(-)-1], isolated from Illicium merrillianum in 2000, possesses neurite outgrowth activity in cultures of fetal rat cortical neurons, and, therefore, is expected to show therapeutic potential for the treatment of neurodegeneration associated with Alzheimer's and Parkinson's diseases. A part from its biological aspects, the caged pentacyclic skeleton of 1 poses interesting synthetic challenges. Here, we report the total synthesis of the unnatural enantiomer of merrilactone A [(+)-1], based on a novel desymmetrization strategy. The chiral lithium amide 16g promoted an enantioselective transannular aldol reaction of eight-membered meso-diketone 3d, establishing the absolute stereochemistries of four chiral centers of the cis-bicyclo[3.3.0]octane framework of 1 in a single step. The obtained compound 4d served as a platform for the subsequent functional group manipulations necessary for the construction of (+)-1. Surprisingly, both the natural and unnatural enantiomers of synthetic merrilactone A equally promoted neurite outgrowth in primary neuronal cultures.
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UR - http://www.scopus.com/inward/citedby.url?scp=34247183754&partnerID=8YFLogxK
U2 - 10.1021/jo0700474
DO - 10.1021/jo0700474
M3 - Article
C2 - 17355151
AN - SCOPUS:34247183754
VL - 72
SP - 3065
EP - 3075
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
SN - 0022-3263
IS - 8
ER -