Abstract
Zerumbone (1) and its 6,7-epoxide (2) react with ammonia and dimethylamine regio- and stereospecifically, affording monoamines 3, 4, 7 and 8. All adducts have the same relative configuration at C2 and C3. The conjugate amination is thermodynamically controlled to arrive at a single diastereomer. At 15°C 7 reacts with cyanide to give aminonitrile 10 as the single product, while at 30°C, acyclic aminonitrile 11 is also formed. The reaction with 8 affords at 0°C bicyclic aminonitrile 12 of the asteriscane skeleton, while at 30°C or higher temperature, mixtures of 12 and tricyclic nitriles 13 and 13′ are obtained. Refluxing of 7, 8 and 10 in aqueous acetonitrile promotes scission of the zerumbone ring by retro-Mannich reaction to provide acyclic aldehydes 16-18, respectively. The dimethylamino group of 7, 8 and 10 is eliminated stereospecifically by Cope- and base-catalyzed eliminations to regenerate the zerumbone skeleton in the products 1, 2 and 21. Cope elimination of 12 results in a mixture of 13 and 13′ by deaminative transannular etherification.
| Original language | English |
|---|---|
| Pages (from-to) | 4857-4866 |
| Number of pages | 10 |
| Journal | Tetrahedron |
| Volume | 59 |
| Issue number | 26 |
| DOIs | |
| Publication status | Published - 23 Jun 2003 |
| Externally published | Yes |
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Keywords
- Asteriscane
- Cope elimination
- Retro-Mannich
- Sesquiterpene
- Transannular
- Zerumbone
ASJC Scopus subject areas
- Biochemistry
- Organic Chemistry
- Drug Discovery
Cite this
The chemistry of zerumbone. Part 5 : Structural transformation of the dimethylamine derivatives. / Kitayama, Takashi; Yokoi, Taketo; Kawai, Yasushi; Hill, Richard K.; Morita, Masanori; Okamoto, Tadashi; Yamamoto, Yukio; Fokin, Valery V.; Sharpless, K. Barry; Sawada, Seiji.
In: Tetrahedron, Vol. 59, No. 26, 23.06.2003, p. 4857-4866.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The chemistry of zerumbone. Part 5
T2 - Structural transformation of the dimethylamine derivatives
AU - Kitayama, Takashi
AU - Yokoi, Taketo
AU - Kawai, Yasushi
AU - Hill, Richard K.
AU - Morita, Masanori
AU - Okamoto, Tadashi
AU - Yamamoto, Yukio
AU - Fokin, Valery V.
AU - Sharpless, K. Barry
AU - Sawada, Seiji
PY - 2003/6/23
Y1 - 2003/6/23
N2 - Zerumbone (1) and its 6,7-epoxide (2) react with ammonia and dimethylamine regio- and stereospecifically, affording monoamines 3, 4, 7 and 8. All adducts have the same relative configuration at C2 and C3. The conjugate amination is thermodynamically controlled to arrive at a single diastereomer. At 15°C 7 reacts with cyanide to give aminonitrile 10 as the single product, while at 30°C, acyclic aminonitrile 11 is also formed. The reaction with 8 affords at 0°C bicyclic aminonitrile 12 of the asteriscane skeleton, while at 30°C or higher temperature, mixtures of 12 and tricyclic nitriles 13 and 13′ are obtained. Refluxing of 7, 8 and 10 in aqueous acetonitrile promotes scission of the zerumbone ring by retro-Mannich reaction to provide acyclic aldehydes 16-18, respectively. The dimethylamino group of 7, 8 and 10 is eliminated stereospecifically by Cope- and base-catalyzed eliminations to regenerate the zerumbone skeleton in the products 1, 2 and 21. Cope elimination of 12 results in a mixture of 13 and 13′ by deaminative transannular etherification.
AB - Zerumbone (1) and its 6,7-epoxide (2) react with ammonia and dimethylamine regio- and stereospecifically, affording monoamines 3, 4, 7 and 8. All adducts have the same relative configuration at C2 and C3. The conjugate amination is thermodynamically controlled to arrive at a single diastereomer. At 15°C 7 reacts with cyanide to give aminonitrile 10 as the single product, while at 30°C, acyclic aminonitrile 11 is also formed. The reaction with 8 affords at 0°C bicyclic aminonitrile 12 of the asteriscane skeleton, while at 30°C or higher temperature, mixtures of 12 and tricyclic nitriles 13 and 13′ are obtained. Refluxing of 7, 8 and 10 in aqueous acetonitrile promotes scission of the zerumbone ring by retro-Mannich reaction to provide acyclic aldehydes 16-18, respectively. The dimethylamino group of 7, 8 and 10 is eliminated stereospecifically by Cope- and base-catalyzed eliminations to regenerate the zerumbone skeleton in the products 1, 2 and 21. Cope elimination of 12 results in a mixture of 13 and 13′ by deaminative transannular etherification.
KW - Asteriscane
KW - Cope elimination
KW - Retro-Mannich
KW - Sesquiterpene
KW - Transannular
KW - Zerumbone
UR - http://www.scopus.com/inward/record.url?scp=0038176337&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0038176337&partnerID=8YFLogxK
U2 - 10.1016/S0040-4020(03)00667-7
DO - 10.1016/S0040-4020(03)00667-7
M3 - Article
VL - 59
SP - 4857
EP - 4866
JO - Tetrahedron
JF - Tetrahedron
SN - 0040-4020
IS - 26
ER -