<p>  </p> <p><em>Streptomyces</em> bacteria use γ-butyrolactone (GBL) hormones to signal biosynthesis of natural products, many of which are useful as medicines, agricultural chemicals, and chemical tools. These GBL hormones have been the target of synthetic efforts for over a decade due to their promising potential to unlock novel natural products that can aid in the fight against cancer, fungal infections, bacterial infections, and more. However, previous syntheses of the <em>Streptomyces coelicolor</em> GBLs suffer from lengthy syntheses, low yields, low enantioselectivity or diastereoselectivity, or lack of diversifiability. The work described herein bypasses each of these issues. The synthesis is shorter than previous efforts, accessing the final molecules in six steps while also having high enantioselectivity, diastereoselectivity, and overall yield. In addition, work has begun to create derivatives of these natural GBLs using five-membered lactam and thiolactone cores, which could have greater stability than the traditional lactone GBL core.</p>

The thesis entitled “Synthesis and applications of 1,4-diketones and γ-oxobutyramides derived from tartaric acid” is divided into two chapters. Chapter 1: Synthesis of TADDOL analogues by nucleophilic addition reactions and their application to the synthesis of α-methoxy arylacetic acid derivatives Synthesis of various TADDOL analogues by the addition of nucleophiles to 1,4-diketones derived from L-(+)-tartaric acid is presented in this chapter. It is found that the reduction of 1,4-Diketones 1a-d with K-Selectride pre-complexed with 18-crown-6 which is the optimized condition to attain better diastereoselectivity towards the C2-symmetric isomer 2a-d (Scheme 1). Addition of Grignard reagents to diketones 1a, 1eh is dependent on nature of Grignard reagents, solvent and temperature. (Structural formula) Scheme 1: Synthesis of TADDOL analogues Application of the synthesized TADDOL analogues in synthesis of enantiopure α-methoxy arylacetic acid derivatives is discussed. The C2-symmetric 1,4-diols 2a-d (TADDOL analogues) are utilized in the synthesis of enantiopure α-methoxy arylacetic acid derivatives as shown in scheme 2. Scheme 2: Synthesis of α-methoxy arylacetic acid derivatives. (SF) Both enantiomers of α-alkyl-α-methoxy arylacetic acids 13a-b and ent-13a are synthesized from the respective C2-symmetric diols 5a-b and 7a-b (scheme 3). (SF) Scheme 3: Synthesis of both enantiomers of α-alkyl-α-methoxy arylacetic acids. Chapter 2: Facile Synthesis of α,β-dihydroxy-γ-butyrolactones and jaspine B from γ-oxobutyramides derived from tartaric acid A short and efficient route for the synthesis of γ-alkyl/aryl-α,β-dihydroxy-γ-butyrolactones 15a-j is accomplished from γ-oxobutyramides 14a-l derived from tartaric acid. Key step includes a controlled addition of Grignard reagent and stereoselective reduction (Scheme 4). (sF) Scheme 4: Synthesis of α,β-dihydroxy-γ-butyrolactones and jaspine B. Utility of the γ-oxobutyramides is further exemplified in the synthesis of jaspine B 18 a cytotoxic anhydrophytosphingosine in 48% overall yield (Scheme 5). (SF) . Scheme 5: Synthesis of α,β-dihydroxy-γ-butyrolactones and jaspine B. Appendix: Serendipitous observation of polymorphism in TADDOL analogue induced by the presence of chiral impurity Polymorphism in one of the TADDOL analogues is serendipitously observed and demonstrated that the 2% impure diastereomer is responsible for the formation of one of the pol ymorphic crystals (Figure 1). (SF) Figure 1: Diastereomeric impurity induced polymorphism. (For structural formula pl see the pdf file)

A bifunctional imidazolium linker was used for the production of highly crosslinked element organic frameworks by Suzuki-coupling with tetrafunctional boronic acids. The resulting porous materials are good heterogeneous organocatalysts in the N-heterocyclic carbene-catalyzed conjugated umpolung of α,β-unsaturated cinnamaldehyde. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

A bifunctional imidazolium linker was used for the production of highly crosslinked element organic frameworks by Suzuki-coupling with tetrafunctional boronic acids. The resulting porous materials are good heterogeneous organocatalysts in the N-heterocyclic carbene-catalyzed conjugated umpolung of α,β-unsaturated cinnamaldehyde. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.