| 5. |
- Larsson, Michael, 1970-
(författare)
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Natural products from nonracemie building blocks : synthesis of pine sawfly pheromones
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 6. |
- Palmgren, Myrna, 1970-
(författare)
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Optimal Truck Scheduling : Mathematical Modeling and Solution by the Column Generation Principle
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- We consider the daily transportation problem in forestry which arises when transporting logs from forest sites to customers such as sawmills and pulp and paper mills. Each customer requires a specific amount of a certain assortment, and the deliveries to the customers can be made within time intervals, known as time windows. Further, there are a number of supply points, each with a certain assortment, and a number of vehicles of a given capacity, to be used for transport.The log truck scheduling problem consists of finding a set of minimal costs routes, one for each vehicle, such that the customers’ demands are satisfied without exceeding the supplies available at the supplies. Each route has to satisfy a number of constraints concerning time windows, truck capacity, timetable of the driver, lunch breaks, et cetera. The model used to describe the log truck scheduling problem is based on the route concept, and each variable, or column, represents one feasible route. Since the number of feasible routes is huge, we work only with restricted versions of this problem, which are similar to restricted master problems in a Dantzig-Wolfe decomposition scheme.We use three solution methods based on the column generation principle, together with a pool strategy which allows us to deal with the feasible routes outside the restricted master problem. The three methods proposed have a common structure; they use branch-andprice together with a column generator, followed by branch-and-bound. The column generators in the three methods differ. In the first method, the subproblem is based on a cluster-first-route-second strategy. The column generator in the second method involves solving a constrained shortest path problem, and finally, the third method builds on a repeated generation of clusters and routes.The three methods are tested on real cases from Swedish forestry companies, and the third method has been adapted to a computerised system that utilises the Swedish national road data base, for computing travelling distances. The results obtained show that the optimisation methods succeed in finding significantly better solutions than those obtained by manual planning, and in a reasonable computing time.
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