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Syntheses of the sixteen stereoisomers of 3,7,11-trimethyl-2-tridecanol, including the (2S,3S,7S,11R) and (2S,3S,7S,11S) stereoisomers identified as pheromone precursors in females of the pine sawfly Microdiprion pallipes (Hymenoptera : Diprionidae).: Diprionidae)
Mittuniversitetet i Sundsvall.
Mittuniversitetet i Sundsvall.
Mittuniversitetet i Sundsvall.
Mittuniversitetet i Sundsvall.
2001 (English)In: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, no 2, 353-363 p.Article in journal (Refereed) Published
Abstract [en]

All sixteen stereoisomers of 3,7,11-trimethyl-2-tridecanol were synthesised in high stereoisomerical purities (> 95%), for use in the identification of the stereoisomers present in females of the pine sawfly Microdiprion pallipes (Fallen) (Hymenoptera: Diprionidae) as the precursor of the actual sex pheromone (which is the propionate), and also for investigation of the biological activities of the esters. The key step in the syntheses was the coupling of each of the enantiomers of cis-3,4-dimethyl-gamma -butyrolactone with each of the four pure stereoisomers of 1-lithio-2,6-dimethyloctanes. The four corresponding alcohols were obtained by lipase-catalysed (Amano PS) kinetic separation, based on selective acylation of either (2R/S,6S)- or (2R/S,GR)-2,6-dimethyl-1-octanol (obtained from the optically pure enantiomers of citronellal). Additionally, a mixture of the 16 possible stereoisomers of 3,7,11-trimethyl-2-tridecanol was also prepared.

Place, publisher, year, edition, pages
2001. no 2, 353-363 p.
Keyword [en]
Asymmetric synthesis, Lipase, Microdiprion pallipes, Pheromones, Total synthesis, 3, 7, 11 trimethyl 2 tridecanol, alcohol, decanol, ester, gamma butyrolactone derivative, lactone derivative, octanol, propionic acid, sex pheromone, triacylglycerol lipase, unclassified drug, acylation, article, drug activity, enantiomer, enzyme kinetics, female, fly, Hymenoptera, nonhuman, stereoisomerism, synthesis
National Category
Organic Chemistry
Identifiers
URN: urn:nbn:se:kth:diva-25543DOI: 10.1002/1099-0690(200101)2001:2<353ISI: 000166621900015OAI: oai:DiVA.org:kth-25543DiVA: diva2:359081
Note
QC 20101026Available from: 2010-10-26 Created: 2010-10-26 Last updated: 2017-12-12Bibliographically approved
In thesis
1. Natural products from nonracemie building blocks: synthesis of pine sawfly pheromones
Open this publication in new window or tab >>Natural products from nonracemie building blocks: synthesis of pine sawfly pheromones
2005 (English)Doctoral thesis, comprehensive summary (Other scientific)
Abstract [en]

This thesis describes a number of synthetic approaches for obtaining chiral, enantiomerically pure natural products, in particular some semiochemicals. This has been accomplished by using various strategies; by starting from compounds from the chiral pool, by using chiral auxiliaries, via enzymatic resolutions or by chemical asymmetric synthesis.

Hence, the sexual pheromone of Microdiprion pallipes, a propanoate ester of one or several isomers of 3,7,11-trimethyltridecan-2-ol, was synthesised, both as a mixture of all isomers and as the sixteen pure, individual stereoisomers. These compounds were obtained by joining different enantiopure building blocks stemming from the chiral pool.

When compared with some synthetic blends, both the propanoate esters of the stereoisomeric erythro-3,7,11-trimethyltridecan-2-ols originally found in the extract from the female of M. pallipes, surprisingly, showed lower activities in biological studies. Indeed, the propanoates of two threo-isomers gave significantly higher responses in biological tests, than did the propanoates of the two natural erythro-ones. Because the synthetic strategy used earlier was not very efficient for the preparation of the threo-isomers of 3,7,11-trimethyltridecan-2-ol, we were encouraged to look for alternative synthetic approaches.

The new synthetic strategy chosen led us to two key synthetic building blocks, an O-protected derivative of (2S,3S)-3-methyl-4-(phenylsulfonyl)butan-2-ol butanol and (3R,7R)-1-iodo-3,7-dimethylnonane. Deprotonation of the former followed by alkylation with the latter should give a compound with the desired carbon skeleton.

For efficient preparation of the first building block, we developed a new diastereoselective addition reaction of dialkylzincs to some chiral aldehydes, the products of which were diastereomerically enriched 1,2-dialkyl-alkanols. Using this method, each enantiomer of the desired building block was obtained via efficient diastereoselective addition of dimethylzinc to each enantiomer of a 2-methylaldehyde. The resulting product, a diastereomerically and enantiomerically highly enriched 3-methyl-2-alkanol was further purified by enzyme catalysed acylation followed by some functional group interconversions.

The second building block was prepared via convergent multistep synthesis, starting from a single, enantiomerically pure compound, (R)-2-methylsuccinic acid 4-t-butyl ester, derived from the chiral pool.

The two enantiomerically pure building blocks, so obtained, were coupled together. Some additional functional group manipulations of the product produced furnished the desired isomer, which had shown the highest activity in field tests of the M. pallipes, namely the propanoate ester of (2S,3R,7R,11R)-3,7,11-trimethyltridecan-2-ol.

This thesis describes a number of synthetic approaches for obtaining chiral, enantiomerically pure natural products, in particular some semiochemicals. This has been accomplished by using various strategies; by starting from compounds from the chiral pool, by using chiral auxiliaries, via enzymatic resolutions or by chemical asymmetric synthesis.

Hence, the sexual pheromone of Microdiprion pallipes, a propanoate ester of one or several isomers of 3,7,11-trimethyltridecan-2-ol, was synthesised, both as a mixture of all isomers and as the sixteen pure, individual stereoisomers. These compounds were obtained by joining different enantiopure building blocks stemming from the chiral pool.

When compared with some synthetic blends, both the propanoate esters of the stereoisomeric erythro-3,7,11-trimethyltridecan-2-ols originally found in the extract from the female of M. pallipes, surprisingly, showed lower activities in biological studies. Indeed, the propanoates of two threo-isomers gave significantly higher responses in biological tests, than did the propanoates of the two natural erythro-ones. Because the synthetic strategy used earlier was not very efficient for the preparation of the threo-isomers of 3,7,11-trimethyltridecan-2-ol, we were encouraged to look for alternative synthetic approaches.

The new synthetic strategy chosen led us to two key synthetic building blocks, an O-protected derivative of (2S,3S)-3-methyl-4-(phenylsulfonyl)butan-2-ol butanol and (3R,7R)-1-iodo-3,7-dimethylnonane. Deprotonation of the former followed by alkylation with the latter should give a compound with the desired carbon skeleton.

For efficient preparation of the first building block, we developed a new diastereoselective addition reaction of dialkylzincs to some chiral aldehydes, the products of which were diastereomerically enriched 1,2-dialkyl-alkanols. Using this method, each enantiomer of the desired building block was obtained via efficient diastereoselective addition of dimethylzinc to each enantiomer of a 2-methylaldehyde. The resulting product, a diastereomerically and enantiomerically highly enriched 3-methyl-2-alkanol was further purified by enzyme catalysed acylation followed by some functional group interconversions.

The second building block was prepared via convergent multistep synthesis, starting from a single, enantiomerically pure compound, (R)-2-methylsuccinic acid 4-t-butyl ester, derived from the chiral pool.

The two enantiomerically pure building blocks, so obtained, were coupled together. Some additional functional group manipulations of the product produced furnished the desired isomer, which had shown the highest activity in field tests of the M. pallipes, namely the propanoate ester of (2S,3R,7R,11R)-3,7,11-trimethyltridecan-2-ol.

This thesis describes a number of synthetic approaches for obtaining chiral, enantiomerically pure natural products, in particular some semiochemicals. This has been accomplished by using various strategies; by starting from compounds from the chiral pool, by using chiral auxiliaries, via enzymatic resolutions or by chemical asymmetric synthesis.

Hence, the sexual pheromone of Microdiprion pallipes, a propanoate ester of one or several isomers of 3,7,11-trimethyltridecan-2-ol, was synthesised, both as a mixture of all isomers and as the sixteen pure, individual stereoisomers. These compounds were obtained by joining different enantiopure building blocks stemming from the chiral pool.

When compared with some synthetic blends, both the propanoate esters of the stereoisomeric erythro-3,7,11-trimethyltridecan-2-ols originally found in the extract from the female of M. pallipes, surprisingly, showed lower activities in biological studies. Indeed, the propanoates of two threo-isomers gave significantly higher responses in biological tests, than did the propanoates of the two natural erythro-ones. Because the synthetic strategy used earlier was not very efficient for the preparation of the threo-isomers of 3,7,11-trimethyltridecan-2-ol, we were encouraged to look for alternative synthetic approaches.

The new synthetic strategy chosen led us to two key synthetic building blocks, an O-protected derivative of (2S,3S)-3-methyl-4-(phenylsulfonyl)butan-2-ol butanol and (3R,7R)-1-iodo-3,7-dimethylnonane. Deprotonation of the former followed by alkylation with the latter should give a compound with the desired carbon skeleton.

For efficient preparation of the first building block, we developed a new diastereoselective addition reaction of dialkylzincs to some chiral aldehydes, the products of which were diastereomerically enriched 1,2-dialkyl-alkanols. Using this method, each enantiomer of the desired building block was obtained via efficient diastereoselective addition of dimethylzinc to each enantiomer of a 2-methylaldehyde. The resulting product, a diastereomerically and enantiomerically highly enriched 3-methyl-2-alkanol was further purified by enzyme catalysed acylation followed by some functional group interconversions.

The second building block was prepared via convergent multistep synthesis, starting from a single, enantiomerically pure compound, (R)-2-methylsuccinic acid 4-t-butyl ester, derived from the chiral pool.

The two enantiomerically pure building blocks, so obtained, were coupled together. Some additional functional group manipulations of the product produced furnished the desired isomer, which had shown the highest activity in field tests of the M. pallipes, namely the propanoate ester of (2S,3R,7R,11R)-3,7,11-trimethyltridecan-2-ol.

Place, publisher, year, edition, pages
Stockholm: KTH, 2005. ix, 60 p.
Series
Trita-IOK, ISSN 1100-7974 ; 2005:94
Keyword
Organic chemistry, Total synthesis, diastereoselective addition, dimethylzinc, Lewis acid, alkyllithium, Organisk kemi
National Category
Organic Chemistry
Identifiers
urn:nbn:se:kth:diva-128 (URN)91-7283-952-X (ISBN)
Public defence
2005-02-18, Sal 0102, Åkroken, Mittuniversitetet, Sundsvall, 10:00 (English)
Opponent
Supervisors
Note
QC 20101026Available from: 2008-12-11 Created: 2008-12-11 Last updated: 2010-10-26Bibliographically approved

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